NZ620037B2

NZ620037B2 - Tricyclic heterocyclic compounds and jak inhibitors

Info

Publication number: NZ620037B2
Application number: NZ620037A
Authority: NZ
Inventors: Keishi Hayashi; Junji Kamon; Masataka Minami; Mariko Nasu; Koji Toyama; Miyuki Uni; Tsuneo Watanabe
Original assignee: Nissan Chemical Industries Ltd
Priority date: 2011-08-12
Filing date: 2012-08-10
Publication date: 2016-01-06

Abstract

Provided are tripyrimidine and tricyclic pyridine compounds, of the general formulae (Ia) and (Ib), where the variables are as defined in the specification. Examples of the compounds include 2-(4-{[4-(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin-1-yl)piperidin-1-yl]methyl}phenoxy)acetonitrile, 1-{trans-4-[(3-hydroxyazetidin-1-yl)methyl]cyclohexyl}-1H-pyrrolo[3',2':5,6] pyrido[4,3-d]pyrimidine-2,4 (3H,7H)-dione, and 1-(trans-4-(hydroxymethyl)cyclohexyl)-1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one. The compounds are inhibitors of Janus kinase (JAK). The compounds may be useful in the treatment of autoimmune, inflammatory and allergic diseases. -{trans-4-[(3-hydroxyazetidin-1-yl)methyl]cyclohexyl}-1H-pyrrolo[3',2':5,6] pyrido[4,3-d]pyrimidine-2,4 (3H,7H)-dione, and 1-(trans-4-(hydroxymethyl)cyclohexyl)-1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one. The compounds are inhibitors of Janus kinase (JAK). The compounds may be useful in the treatment of autoimmune, inflammatory and allergic diseases.

Description

DESCRIPTION TRICYCLIC HETEROCYCLIC COMPOUNDS AND JAK INHIBITORS TECHNICAL FIELD The present invention relates to novel tricyclic pyrimidine compounds and tricyclic pyridine compounds having JAK inhibitory activities.

BACKGROUND ART The JAK (Janus kinase) family is a tyrosine kinase family consisting of four members, JAK1, JAK2, JAK3 and Tyk2 (Tyrosine kinase 2) and plays an important role in cytokine signaling.

While the kinases of this family, except for JAK3, are widely expressed in tissues, expression of JAK3 is restricted to immune cells. This is consistent with the fact that JAK3 plays an important role in various receptor-mediated signaling pathways such as IL (interleukin)-2, IL-4, IL-7, IL-9, IL-15 and IL-21 signaling by noncovalently associating with the common γ chain (Non-Patent Documents 1 and 2).

Lowered JAK3 protein levels or defects in the common γ chain gene observed in patients with an immunodeficiency called X-linked Severe Combined Immuno Defficiency (XSCID) suggest that blocking of the JAK3 signaling pathway leads to immunosuppression (Non-Patent Documents 3 and 4). Animal experiments indicate the importance of JAK3 not only in maturation of B- and T-lymphocytes but also in maintenance of T-lymphocyte functions. Therefore, regulation of immune responses via this mechanism is a promising therapy for T-cell lymphoproliferative diseases such as organ transplant rejection and autoimmune diseases.

Analyses of JAK1 knockout mice and JAK1-deficient cells suggest involvement of JAK1 in various receptor-mediated signaling pathways such as IFN (Interferon)α, IFNβ, IFNγ, IL-2, IL-4, IL-6, IL-7 and IL-15 signaling (Non-Patent Document 5). Therefore, regulation of inflammatory responses via these signaling pathways is therapeutically promising for treatment of diseases involving macrophage and lymphocyte activation such as autoimmune diseases and acute and chronic organ transplant rejection.

Analyses of JAK2 knockout mice and JAK2-deficient cells suggest involvement of JAK2 in various receptor-mediated signaling pathways such as EPO (Erythropoietin) α, thrombopoietin, IFNγ, IL-3 and GM-CSF signaling (Non-Patent Documents 6, 7 and 8).

These signaling pathways are supposed to mediate differentiation of erythrocyte or thrombocyte progenitor cells in bone marrow. Meanwhile, it is suggested that a substitution of phenylalanine-617 with valine in JAK2 is associated with myeloproliferative diseases (Non-Patent Document 6). Therefore, regulation of differentiation of myeloid progenitor cells via these signaling pathways is therapeutically promising for treatment of myeloproliferative diseases. 40 The JAK inhibitor CP-690,550 is reported to have improved the pathology of rheumatoid arthritis and psoriasis in clinical tests (Non-Patent Documents 9 and 10) and suppressed rejection in a monkey model of kidney transplantation and airway inflammation in a murine asthma model (Non-Patent Documents 11 and 12). From these findings, immunosuppression by JAK inhibitors is considered to be useful for 45 prevention or treatment of organ transplant rejection and post-transplant graft-versus- host reaction, autoimmune diseases and allergic diseases. Although other compounds having JAK inhibitory action than CP-690,550 have been reported (Patent Documents 1 t o11), development of more of such compounds is demanded.

PRIOR ART DOCUMENT Patent Document 1: WO01/42246 Patent Document 2: WO2008/084861 Patent Document 3: WO2010/119875 Patent Document 4: WO2011/045702 Patent Document 5: WO2011/068881 Patent Document 6: WO2011/075334 Patent Document 7: WO2007/007919 Patent Document 8: WO2007/077949 Patent Document 9: WO2009/152133 Patent Document 10: WO2011/086053 Patent Document 11: WO2011/068899 Non-Patent Document 1: Cell, 2002, 109, pp. S121-131 Non-Patent Document 2: Science, 2002, 298, pp., 1630-1634 Non-Patent Document 3: Nature, 1995, 377, pp. 65-68 Non-Patent Document 4: Science, 1995, 270, pp. 797-800 Non-Patent Document 5: J. Immunol., 2007, 178, pp. 2623-2629 Non-Patent Document 6: Pathol. Biol., 2007, 55, pp. 88-91 Non-Patent Document 7: Cancer Genet. Cytogenet., 2009, 189, pp. 43-47 Non-Patent Document 8: Semin. Cell. Dev. Biol., 2008, 19, pp. 385-393 Non-Patent Document 9: Arthritis Rheum., 2009, 60, pp. 1895-1905 Non-Patent Document 10: J. Invest. Dermatol., 2009, 129, pp. 2299-2302 Non-Patent Document 11: Science, 2003, 302, pp. 875-878 Non-Patent Document 12: Eur. J. Pharmacol., 2008, 582, pp. 154-161 DISCLOSURE OF THE INVENTION TECHNICAL PROBLEM The object of the present invention is to provide novel drug compounds having excellent JAK inhibitory activities useful for prevention or treatment of autoimmune diseases, inflammatory diseases and allergic diseases.

SOLUTION TO PROBLEMS As a result of their extensive research in search of new low-molecular-weight compounds having JAK inhibitory activities, the present inventors found that the compounds of the present invention have high inhibitory action and accomplished the present invention. Herein described is: (1) A compound represented by the formula (I ): (R ) a ( I ) a a a [wherein the ring A is represented by the following formula (II -1) or the formula (II -2): ( II ) (II -1 ) (II -2 ) 1a 4a 1a 5a 2a (wherein T is a nitrogen atom or CR , U is a nitrogen atom or CR , T is a single 7a 8a 2a bond or CR R , and E is an oxygen atom or a sulfur atom), a 9a X is a nitrogen atom or CR , a 10a Y is CR , R is a hydrogen atom, a halogen atom, a C alkyl group or a C haloalkyl group, 1-6 1-6 the ring B is a C cycloalkane, a C cycloalkene (a ring-constituting methylene 3-11 3-11 group of the C cycloalkane and the C cycloalkene may be replaced by a carbonyl 3-11 3-11 group), a 3 to 14-membered non-aromatic heterocycle, a C aromatic carbocycle or a 6-14 to 10-membered aromatic heterocycle, L is a single bond, a C alkylene group, a C alkenylene group or a C alkynylene 1-6 2-6 2-6 group (the C alkylene group, the C alkenylene group and the C alkynylene group 1-6 2-6 2-6 are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, amino groups, cyano groups and nitro groups), L is a single bond, a C alkylene group, a C alkenylene group, a C alkynylene 1-6 2-6 2-6 group (the C alkylene group, the C alkenylene group and the C alkynylene group 1-6 2-6 2-6 are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, 15a 15a amino groups, cyano groups and nitro groups), =C(R )- (wherein R is a hydrogen a 2a atom or a cyano group, and the bond connecting the ring B and L is a double bond) 15a 15a or =C(R )-CH - (wherein R is a hydrogen atom or a cyano group, and the bond a 2a connecting the ring B and L is a double bond), 3a a a L is a single bond or represented by any of the following formulae (III -1) to (III -20) and the formula (XIII ): O S S a a O 12 1 O a a R E (III -1 ) (III -2 ) a a a a ( III -3 ) ( III -4 ) (III -5 ) (III -6 ) 1 O O 1 13a a a a a a (III -7 ) ( III -8 ) ( III -9 ) ( III -10 ) (III -11 ) ( III ) a 1 1a N N N N 12a a a a 12 12 13 R R R a a a a a (III -12 ) ( III -13 ) (III -14 ) (III -15 ) ( III -16 ) a 1a 14a O N N N N N a a a a 12a a 12 13 12 13 R R R R a a a a ( III -17 ) (III -18 ) ( III -19 ) ( III -20 ) 1a 11a (wherein E is an oxygen atom, a sulfur atom or NR ), 3a 2a when L is a single bond, R is a hydrogen atom, a halogen atom, an azido group, a C cycloalkyl group, a 3 to 14-membered non-aromatic heterocyclyl group, a C aryl 3-11 6-14 group, a 5 to 10-membered aromatic heterocyclyl group, a 8 to 14-membered partially saturated aromatic cyclic group or a 8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon group (the C cycloalkyl group, the 3 to 14-membered non- 3-11 aromatic heterocyclyl group, the C aryl group, the 5 to 10-membered aromatic 6-14 heterocyclyl group, the 8 to 14-membered partially saturated aromatic cyclic group and the 8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of the substituent set V , substituent set V and C alkyl groups (the C alkyl groups are substituted with a C 1-6 1-6 1-6 alkoxycarbonylamino group (the C alkoxycarbonylamino group is unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms))), 3a 2a when L is not a single bond, R is a hydrogen atom, a C alkyl group, a C alkenyl 1-6 2-6 group, a C alkynyl group (the C alkyl group the C alkenyl group and the C 2-6 1-6 2-6 2-6 alkynyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V and the substituent set V ), a C cycloalkyl group, a 3 to 14-membered non-aromatic heterocyclyl group, a 3-11 C aryl group, a 5 to 10-membered aromatic heterocyclyl group, a 8 to 14-membered 6-14 partially saturated aromatic cyclic group or a 8 to 14-membered aromatic ring- condensed alicyclic hydrocarbon group (the C cycloalkyl group, the 3 to 14- 3-11 membered non-aromatic heterocyclyl group, the C aryl group, the 5 to 10-membered 6-14 aromatic heterocyclyl group, the 8 to 14-membered partially saturated aromatic cyclic group and the 8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon group are unsubstituted or substituted with one or more identical or different substituents 4a 9a independently selected from the substituent set V and the substituent set V ), n is 0, 1 or 2, R is a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a sulfamoyl group, a phosphono group, a phosphonooxy group, a sulfo group, a sulfoxy group, a tetrazolyl group, a halogen atom, a cyano group, a nitro group, a C alkyl group, a C haloalkyl group, a C cycloalkyl group, a C alkenyl group, a C 1-6 3-11 2-6 2-6 haloalkenyl group, a C alkoxy group, a C haloalkoxy group, a C alkylthio group, a 1-6 1-6 1-6 C haloalkylthio group, a C alkylcarbonyl group, a C haloalkylcarbonyl group, a C 1-6 1-6 1-6 1- alkylsulfonyl group, a C haloalkylsulfonyl group, a C alkoxycarbonyl group, a 6 1-6 1-6 mono-C alkylamino group, a di-C alkylamino group, a mono-C 1-6 1-6 1-6 alkylaminocarbonyl group, a di-C alkylaminocarbonyl group or a C 1-6 1-6 a 3a alkylcarbonylamino group (when n is 2, R ’s may be identical or different), 4a 5a 7a 8a each of R , R , R and R is independently a hydrogen atom, a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a tetrazolyl group, a halogen atom, a cyano group, a C alkyl group, a C alkenyl group, a C alkoxy group, a C 1-6 2-6 1-6 1-6 alkylthio group, a C alkylcarbonyl group, a C alkylsulfonyl group, a mono-C 1-6 1-6 1-6 alkylamino group, a di-C alkylamino group (the C alkyl group, the C alkenyl group, 1-6 1-6 2-6 the C alkoxy group, the C alkylthio group, the C alkylcarbonyl group, the C 1-6 1-6 1-6 1-6 alkylsulfonyl group, the mono-C alkylamino group and the di-C alkylamino group 1-6 1-6 are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a C alkoxycarbonyl group, a C 1-6 3- cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a C aryl 11 6-14 group or a 5 to 10-membered aromatic heterocyclyl group (the C cycloalkyl group, 3-11 the 3 to 11-membered non-aromatic heterocyclyl group, the C aryl group and the 5 to 6-14 10-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), R is a hydrogen atom, a C alkyl group, a C alkenyl group, a C alkylcarbonyl 1-6 2-6 1-6 group, a C alkylsulfonyl group, a C alkoxycarbonyl group, a mono-C 1-6 1-6 1-6 40 alkylaminocarbonyl group, a di-C alkylaminocarbonyl group (the C alkyl group, the 1-6 1-6 C alkenyl group, the C alkylcarbonyl group, the C alkylsulfonyl group, the C 2-6 1-6 1-6 1-6 alkoxycarbonyl group, the mono-C alkylaminocarbonyl group and the di-C 1-6 1-6 alkylaminocarbonyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a C 3-11 45 cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a C aryl 6-14 group or a 5 to 10-membered aromatic heterocyclyl group (the C cycloalkyl group, 3-11 the 3 to 11-membered non-aromatic heterocyclyl group, the C aryl group and the 5 to 6-14 -membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), 9a 10a each of R and R is independently a hydrogen atom, a halogen atom, a cyano group, a carbamoyl group, a C alkyl group, a C haloalkyl group, a C cycloalkyl group, a 1-6 1-6 3-11 C alkoxy group, a C haloalkoxy group, a C alkylthio group, a C alkylcarbonyl 1-6 1-6 1-6 1-6 group, a C alkylsulfonyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a C aryl group or a 5 to 10-membered aromatic heterocyclyl group, 6-14 R is a hydrogen atom, a hydroxy group, a cyano group, a nitro group, a C alkyl group or a C alkoxy group, 12a 13a 14a each of R , R and R is independently a hydrogen atom, a C alkyl group, a C 1-6 1-6 haloalkyl group (the C alkyl group and the C haloalkyl group are unsubstituted or 1-6 1-6 substituted with one or more identical or different substituents independently selected 2a 8a 9a from the substituent set V , the substituent set V and the substituent set V ), a C 3-11 cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a C aryl 6-14 group, a 5 to 10-membered aromatic heterocyclyl group, a 8 to 14-membered partially saturated aromatic cyclic group or a 8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon group (the C cycloalkyl group, the 3 to 11-membered non- 3-11 aromatic heterocyclyl group, the C aryl group, the 5 to 10-membered aromatic 6-14 heterocyclyl group, the 8 to 14-membered partially saturated aromatic cyclic group and the 8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon group are unsubstituted or substituted with one or more identical or different substituents 4a 9a independently selected from the substituent set V and the substituent set V ), the substituent set V consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C alkyl groups, C haloalkyl groups, C cycloalkyl groups, C alkenyl groups, C 1-6 1-6 3-11 2-6 2-6 haloalkenyl groups, C alkoxy groups, C haloalkoxy groups, C alkylthio groups, C 1-6 1-6 1-6 1- haloalkylthio groups, C alkylcarbonyl groups, C haloalkylcarbonyl groups, C 6 1-6 1-6 1-6 alkylsulfonyl groups, C haloalkylsulfonyl groups, C alkoxycarbonyl groups, 3 to 11- 1-6 1-6 membered non-aromatic heterocyclyl groups, mono-C alkylamino groups, di-C 1-6 1-6 alkylamino groups, mono-C alkylaminocarbonyl groups, di-C alkylaminocarbonyl 1-6 1-6 groups and C alkylcarbonylamino groups, 2a 1a the substituent set V consists of the groups in the substituent set V and C aryl 6-14 groups and 5 to 10-membered aromatic heterocyclyl groups (the C aryl groups and 5 6-14 to 10-membered aromatic heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), the substituent set V consists of hydroxy groups, amino groups, carboxy groups, 40 carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C alkoxy groups, C haloalkoxy groups, C alkylthio groups, C haloalkylthio 1-6 1-6 1-6 1-6 groups, C alkylcarbonyl groups, C haloalkylcarbonyl groups, C alkylsulfonyl 1-6 1-6 1-6 groups, C haloalkylsulfonyl groups, C alkoxycarbonyl groups, mono-C alkylamino 1-6 1-6 1-6 45 groups, di-C alkylamino groups, mono-C alkylaminocarbonyl groups, di-C 1-6 1-6 1-6 alkylaminocarbonyl groups, C alkylcarbonylamino groups, C cycloalkyl groups, 3 to 1-6 3-11 11-membered non-aromatic heterocyclyl groups, C aryl groups and 5 to 10- 6-14 membered aromatic heterocyclyl groups (the C cycloalkyl groups, the 3 to 11- 3-11 membered non-aromatic heterocyclyl groups, the C aryl groups and the 5 to 10- 6-14 membered aromatic heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), the substituent set V consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C alkyl groups, C alkenyl groups, C alkoxy groups, C alkylthio groups, C 1-6 2-6 1-6 1-6 1-6 alkylcarbonyl groups, C alkylsulfonyl groups, C alkoxycarbonyl groups, mono-C 1-6 1-6 1-6 alkylamino groups, di-C alkylamino groups, mono-C alkylaminocarbonyl groups, di- 1-6 1-6 C alkylaminocarbonyl groups, C alkylcarbonylamino groups (the C alkyl groups, 1-6 1-6 1-6 the C alkenyl groups, the C alkoxy groups, the C alkylthio groups, the C 2-6 1-6 1-6 1-6 alkylcarbonyl groups, the C alkylsulfonyl groups, the C alkoxycarbonyl groups, the 1-6 1-6 mono-C alkylamino groups, the di-C alkylamino groups, the mono-C 1-6 1-6 1-6 alkylaminocarbonyl groups, the di-C alkylaminocarbonyl groups and the C 1-6 1-6 alkylcarbonylamino groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), C 3-11 cycloalkyl groups, 3 to 11-membered non-aromatic heterocyclyl groups, C aryl 6-14 groups and 5 to 10-membered aromatic heterocyclyl groups (the C cycloalkyl groups, 3-11 the 3 to 11-membered non-aromatic heterocyclyl groups, the C aryl group and the 5 6-14 to 10-membered aromatic heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), the substituent set V consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C alkoxy groups, C alkylthio groups, C alkylcarbonyl groups, C alkylsulfonyl 1-6 1-6 1-6 1-6 groups, C alkoxycarbonyl groups, mono-C alkylamino groups, di-C alkylamino 1-6 1-6 1-6 groups, mono-C alkylaminocarbonyl groups, di-C alkylaminocarbonyl groups, C 1-6 1-6 1-6 alkylcarbonylamino groups, C cycloalkyl groups, 3 to 11-membered non-aromatic 3-11 heterocyclyl groups, C aryl group and 5 to 10-membered aromatic heterocyclyl 6-14 groups (the C alkoxy groups, the C alkylthio groups, the C alkylcarbonyl groups, 1-6 1-6 1-6 the C alkylsulfonyl groups, the C alkoxycarbonyl groups, the mono-C alkylamino 1-6 1-6 1-6 groups, the di-C alkylamino groups, the mono-C alkylaminocarbonyl groups, the di- 1-6 1-6 C alkylaminocarbonyl groups, the C alkylcarbonylamino groups, the C cycloalkyl 1-6 1-6 3-11 groups, the 3 to 11-membered non-aromatic heterocyclyl groups, the C aryl groups 6-14 and the 5 to 10-membered aromatic heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected 40 from the substituent set V ), the substituent set V consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C alkoxy groups, C alkylthio groups, C alkylcarbonyl groups, C alkylsulfonyl 1-6 1-6 1-6 1-6 45 groups, C alkoxycarbonyl groups, mono-C alkylamino groups, di-C alkylamino 1-6 1-6 1-6 groups, mono-C alkylaminocarbonyl groups, di-C alkylaminocarbonyl groups, C 1-6 1-6 1-6 alkylcarbonylamino groups (the C alkoxy groups, the C alkylthio groups, the C 1-6 1-6 1-6 alkylcarbonyl groups, the C alkylsulfonyl groups, the C alkoxycarbonyl groups, the 1-6 1-6 mono-C alkylamino groups, the di-C alkylamino groups, the mono-C 1-6 1-6 1-6 alkylaminocarbonyl groups, the di-C alkylaminocarbonyl groups and the C 1-6 1-6 alkylcarbonylamino groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), C 3-11 cycloalkyl groups, 3 to 11-membered non-aromatic heterocyclyl groups, C aryl 6-14 groups, 5 to 10-membered aromatic heterocyclyl groups, 8 to 14-membered partially saturated aromatic cyclic groups and 8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon groups (the C cycloalkyl groups, the 3 to 11-membered non- 3-11 aromatic heterocyclyl groups, the C aryl groups and the 5 to 10-membered aromatic 6-14 heterocyclyl groups, the 8 to 14-membered partially saturated aromatic cyclic groups and the 8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon groups are unsubstituted or substituted with one or more identical or different substituents 4a 9a independently selected from the substituent set V and the substituent set V ), the substituent set V consists of C cycloalkyl groups, 3 to 11-membered non- 3-11 aromatic heterocyclyl groups (the C cycloalkyl groups and 3 to 11-membered non- 3-11 aromatic heterocyclyl groups are substituted with one or more identical or different substituent independently selected from the substituent set V ), 8 to 14-membered partially saturated aromatic cyclic groups and 8 to 14-membered aromatic ring- condensed alicyclic hydrocarbon groups (the 8 to 14-membered partially saturated aromatic cyclic groups and the 8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), and the substituent set V consists of mono-C alkylaminosulfonyl groups, di-C 1-6 1-6 alkylaminosulfonyl groups, C alkylsulfonylamino groups, C alkoxycarbonylamino 1-6 1-6 groups (the mono-C alkylaminosulfonyl groups, the di-C alkylaminosulfonyl groups 1-6 1-6 the C alkylsulfonylamino groups and the C alkoxycarbonylamino groups are 1-6 1-6 unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), C cycloalkoxy groups, C 3-6 3-6 cycloalkylamino groups, C cycloalkylthio groups, C cycloalkylcarbonyl groups and 3-6 3-6 C cycloalkylsulfonyl groups (the C cycloalkoxy groups, the C cycloalkylamino 3-6 3-6 3-6 groups, the C cycloalkylthio groups, the C cycloalkylcarbonyl groups and the C 3-6 3-6 3-6 cycloalkylsulfonyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V )], a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (2) The compound according to (1), which is represented by the formula (I ): 1a a (R ) a ( I ) a a a [wherein the ring A is represented by the following formula (II -1) or the formula (II -2): ( II ) (II -1 ) (II -2 ) 1a 4a 1a 5a 2a (wherein T is a nitrogen atom or CR , U is a nitrogen atom or a CR , T is a single 7a 8a 2a bond or CR R , E is an oxygen atom or a sulfur atom), a 9a X is a nitrogen atom or CR , a 10a Y is CR , R is a hydrogen atom, a halogen atom, a C alkyl group or a C haloalkyl group, 1-6 1-6 the ring B is a C cycloalkane, a C cycloalkene, a 3 to 11-membered non-aromatic 3-11 3-11 heterocycle, a C aromatic carbocycle or a 5 to 10-membered aromatic heterocycle, 6-14 L is a single bond, a C alkylene group, a C alkenylene group or a C alkynylene 1-6 2-6 2-6 group (the C alkylene group, the C alkenylene group and the C alkynylene group 1-6 2-6 2-6 are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, amino groups, cyano groups and nitro groups), L is a single bond, a C alkylene group, a C alkenylene group or a C alkynylene 1-6 2-6 2-6 group (the C alkylene group, the C alkenylene group and the C alkynylene group 1-6 2-6 2-6 are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, amino groups, cyano groups and nitro groups), 3a a a L is a single bond or represented by any of the following formulae (III -1) to (III -20) O S S a a O 12 1 O a a R E (III -1 ) (III -2 ) a a a a ( III -3 ) ( III -4 ) (III -5 ) (III -6 ) 1 O O 1 13a a a a a a (III -7 ) ( III -8 ) ( III -9 ) ( III -10 ) (III -11 ) ( III ) a 1 1a N N N N 12a a a a 12 12 13 R R R a a a a a (III -12 ) ( III -13 ) (III -14 ) (III -15 ) ( III -16 ) a 1a 14a O N N N N N a a a a 12a a 12 13 12 13 R R R R a a a a ( III -17 ) (III -18 ) ( III -19 ) ( III -20 ) 1a 11a (wherein E is an oxygen atom, a sulfur atom or NR ), 3a 2a when L is a single bond, R is a hydrogen atom, a halogen atom, a C cycloalkyl 3-11 group, a 3 to 11-membered non-aromatic heterocyclyl group, a C aryl group or a 5 to 6-14 10-membered aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11- 3-11 membered non-aromatic heterocyclyl group, the C aryl group and the 5 to 10- 6-14 membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), 3a 2a when L is not a single bond, R is a hydrogen atom, a C alkyl group, a C alkenyl 1-6 2-6 group (the C alkyl group and the C alkenyl group are unsubstituted or substituted 1-6 2-6 with one or more identical or different substituents independently selected from the substituent set V ), a C cycloalkyl group, a 3 to 11-membered non-aromatic 3-11 heterocyclyl group, a C aryl group or a 5 to 10-membered aromatic heterocyclyl 6-14 group (the C cycloalkyl group, the 3 to 11-membered non-aromatic heterocyclyl 3-11 group, the C aryl group and the 5 to 10-membered aromatic heterocyclyl group are 6-14 unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), n is 0, 1 or 2, R is a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a sulfamoyl group, a phosphono group, a phosphonooxy group, a sulfo group, a sulfoxy group, a tetrazolyl group, a halogen atom, a cyano group, a nitro group, a C alkyl group, a C haloalkyl group, a C cycloalkyl group, a C alkenyl group, a C 1-6 3-11 2-6 2-6 haloalkenyl group, a C alkoxy group, a C haloalkoxy group, a C alkylthio group, a 1-6 1-6 1-6 C haloalkylthio group, a C alkylcarbonyl group, a C haloalkylcarbonyl group, a C 1-6 1-6 1-6 1- alkylsulfonyl group, a C haloalkylsulfonyl group, a C alkoxycarbonyl group, a 6 1-6 1-6 mono-C alkylamino group, a di-C alkylamino group, a mono-C 1-6 1-6 1-6 alkylaminocarbonyl group, a di-C alkylaminocarbonyl group or a C 1-6 1-6 a 3a alkylcarbonylamino group (when n is 2, R ’s may be identical or different), 4a 5a 7a 8a each of R , R , R and R is independently a hydrogen atom, a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a tetrazolyl group, a halogen atom, a cyano group, a C alkyl group, a C alkenyl group, a C alkoxy group, a C 1-6 2-6 1-6 1-6 alkylthio group, a C alkylcarbonyl group, a C alkylsulfonyl group, a mono-C 1-6 1-6 1-6 alkylamino group, a di-C alkylamino group (the C alkyl group, the C alkenyl group, 1-6 1-6 2-6 the C alkoxy group, the C alkylthio group, the C alkylcarbonyl group, the C 1-6 1-6 1-6 1-6 alkylsulfonyl group, the mono-C alkylamino group and the di-C alkylamino group 1-6 1-6 are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a C alkoxycarbonyl group, a C 1-6 3- cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a C aryl 11 6-14 group or a 5 to 10-membered aromatic heterocyclyl group (the C cycloalkyl group, 3-11 the 3 to 11-membered non-aromatic heterocyclyl group, the C aryl group and the 5 to 6-14 -membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), R is a hydrogen atom, a C alkyl group, a C alkenyl group, a C alkylcarbonyl 1-6 2-6 1-6 group, a C alkylsulfonyl group, a C alkoxycarbonyl group, a mono-C 1-6 1-6 1-6 alkylaminocarbonyl group, a di-C alkylaminocarbonyl group (the C alkyl group, the 1-6 1-6 C alkenyl group, the C alkylcarbonyl group, the C alkylsulfonyl group, the C 2-6 1-6 1-6 1-6 alkoxycarbonyl group, the mono-C alkylaminocarbonyl group and the di-C 1-6 1-6 alkylaminocarbonyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a C 3-11 cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a C aryl 6-14 group or a 5 to 10-membered aromatic heterocyclyl group (the C cycloalkyl group, 3-11 the 3 to 11-membered non-aromatic heterocyclyl group, the C aryl group and the 5 to 6-14 -membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), 9a 10a each of R and R is independently a hydrogen atom, a halogen atom, a cyano group, a carbamoyl group, a C alkyl group, a C haloalkyl group, a C cycloalkyl group, a 1-6 1-6 3-11 C alkoxy group, a C haloalkoxy group, a C alkylthio group, a C alkylcarbonyl 1-6 1-6 1-6 1-6 group, a C alkylsulfonyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a C aryl group or a 5 to 10-membered aromatic heterocyclyl group, 6-14 40 R is a hydrogen atom, a hydroxy group, a cyano group, a nitro group, a C alkyl group or a C alkoxy group, 12a 13a 14a each of R , R and R is independently a hydrogen atom, a C alkyl group or a C 1-6 1- haloalkyl group (the C alkyl group and the C haloalkyl group are unsubstituted or 6 1-6 1-6 substituted with one or more identical or different substituents independently selected 45 from the substituent set V ), the substituent set V consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C alkyl groups, C haloalkyl groups, C cycloalkyl groups, C alkenyl groups, C 1-6 1-6 3-11 2-6 2-6 haloalkenyl groups, C alkoxy groups, C haloalkoxy groups, C alkylthio groups, C 1-6 1-6 1-6 1- haloalkylthio groups, C alkylcarbonyl groups, C haloalkylcarbonyl groups, C 6 1-6 1-6 1-6 alkylsulfonyl groups, C haloalkylsulfonyl groups, C alkoxycarbonyl groups, 3 to 11- 1-6 1-6 membered non-aromatic heterocyclyl groups, mono-C alkylamino groups, di-C 1-6 1-6 alkylamino groups, mono-C alkylaminocarbonyl groups, di-C alkylaminocarbonyl 1-6 1-6 groups and C alkylcarbonylamino groups, 2a 1a the substituent set V consists of the groups in the substituent set V , C aryl groups 6-14 and 5 to 10-membered aromatic heterocyclyl groups (the C aryl group and the 5 to 6-14 -membered aromatic heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set the substituent set V consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C alkoxy groups, C haloalkoxy groups, C alkylthio groups, C haloalkylthio 1-6 1-6 1-6 1-6 groups, C alkylcarbonyl groups, C haloalkylcarbonyl groups, C alkylsulfonyl 1-6 1-6 1-6 groups, C haloalkylsulfonyl groups, C alkoxycarbonyl groups, mono-C alkylamino 1-6 1-6 1-6 groups, di-C alkylamino groups, mono-C alkylaminocarbonyl groups, di-C 1-6 1-6 1-6 alkylaminocarbonyl groups, C alkylcarbonylamino groups, C cycloalkyl groups, 3 to 1-6 3-11 11-membered non-aromatic heterocyclyl groups, C aryl groups and 5 to 10- 6-14 membered aromatic heterocyclyl groups (the C cycloalkyl groups, the 3 to 11- 3-11 membered non-aromatic heterocyclyl groups, the C aryl groups and the 5 to 10- 6-14 membered aromatic heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), the substituent set V consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C alkyl groups, C alkenyl groups, C alkoxy groups, C alkylthio groups, C 1-6 2-6 1-6 1-6 1-6 alkylcarbonyl groups, C alkylsulfonyl groups, C alkoxycarbonyl groups, mono-C 1-6 1-6 1-6 alkylamino groups, di-C alkylamino groups, mono-C alkylaminocarbonyl groups, di- 1-6 1-6 C alkylaminocarbonyl groups, C alkylcarbonylamino groups (the C alkyl groups, 1-6 1-6 1-6 the C alkenyl groups, the C alkoxy groups, the C alkylthio groups, the C 2-6 1-6 1-6 1-6 alkylcarbonyl groups, the C alkylsulfonyl groups, the C alkoxycarbonyl groups, the 1-6 1-6 mono-C alkylamino groups, the di-C alkylamino groups, the mono-C 1-6 1-6 1-6 alkylaminocarbonyl groups, the di-C alkylaminocarbonyl groups and the C 1-6 1-6 alkylcarbonylamino groups are unsubstituted or substituted with one or more identical or 40 different substituents independently selected from the substituent set V ), C 3-11 cycloalkyl groups, 3 to 11-membered non-aromatic heterocyclyl groups, C aryl 6-14 groups and 5 to 10-membered aromatic heterocyclyl groups (the C cycloalkyl groups, 3-11 3 to 11-membered non-aromatic heterocyclyl groups, C aryl groups and 5 to 10- 6-14 membered aromatic heterocyclyl groups are unsubstituted or substituted with one or 45 more identical or different substituents independently selected from the substituent set V ), and the substituent set V consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C alkoxy groups, C alkylthio groups, C alkylcarbonyl groups, C alkylsulfonyl 1-6 1-6 1-6 1-6 groups, C alkoxycarbonyl groups, mono-C alkylamino groups, di-C alkylamino 1-6 1-6 1-6 groups, mono-C alkylaminocarbonyl groups, di-C alkylaminocarbonyl groups, C 1-6 1-6 1-6 alkylcarbonylamino groups, C cycloalkyl groups, 3 to 11-membered non-aromatic 3-11 heterocyclyl groups, C aryl groups and 5 to 10-membered aromatic heterocyclyl 6-14 groups (the C alkoxy groups, the C alkylthio groups, the C alkylcarbonyl groups, 1-6 1-6 1-6 the C alkylsulfonyl groups, the C alkoxycarbonyl groups, the mono-C alkylamino 1-6 1-6 1-6 groups, the di-C alkylamino groups, the mono-C alkylaminocarbonyl groups, the di- 1-6 1-6 C alkylaminocarbonyl groups, the C alkylcarbonylamino groups, the C cycloalkyl 1-6 1-6 3-11 groups, the 3 to 11-membered non-aromatic heterocyclyl groups, the C aryl groups 6-14 and the 5 to 10-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V )], a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (3) The compound according to (2), wherein R is a hydrogen atom, a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. a 10a 10a (4) The compound according to (2) or (3), wherein Y is CR (wherein R is a hydrogen atom), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (5) The compound according to any one of (2) to (4), wherein X is a nitrogen atom or 9a 9a CR (wherein R is a hydrogen atom, a halogen atom, a cyano group, a C alkyl group, a C haloalkyl group or a C cycloalkyl group), a tautomer or a 1-3 3-6 pharmaceutically acceptable salt of the compound or a solvate thereof. (6) The compound according to any one of (2) to (5), wherein the ring A is represented by any of the following formulae (IV -1) to (IV -3): N 2a ( IV ) a a a (IV -1 ) (IV -2 ) (IV -3 ) (wherein E is an oxygen atom or a sulfur atom), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (7) The compound according to any one of (2) to (6), wherein L is a single bond, L is a single bond, a C alkylene group or a C alkenylene group (the C alkylene 1-6 2-6 1-6 group and the C alkenylene group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, amino groups, cyano groups and nitro groups), the ring B is a C cycloalkane, a C cycloalkene, a 3 to 11-membered non-aromatic 3-11 3-11 heterocycle, a C aromatic carbocycle or a 5 to 10-membered an aromatic 6-14 heterocycle, 40 n is 0 or 1, R is a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a tetrazolyl group, a halogen atom, a cyano group, a nitro group, a C alkyl group, a C 1-3 1-3 haloalkyl group, a C cycloalkyl group, a C alkoxy group, a C haloalkoxy group or 3-6 1-3 1-3 a C alkylsulfonyl group, L is a single bond, and R is a hydrogen atom, a halogen atom, a C cycloalkyl group, a 3 to 11-membered 3-11 non-aromatic heterocyclyl group, a phenyl group, a naphthyl group or a 5 to 10- membered aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11- 3-11 membered non-aromatic heterocyclyl group, the phenyl group, the naphthyl group and the 5 to 10-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (8) The compound according to any one of (2) to (6), wherein L is a single bond or a C alkylene group, L is a single bond or a C alkylene group (the C alkylene group is unsubstituted or 1-3 1-3 substituted with a cyano group or a C haloalkyl group), the ring B is a C cycloalkane, a C cycloalkene, a 3 to 11-membered non-aromatic 3-11 3-11 heterocycle, benzene or a 5 to 6-membered aromatic heterocycle, n is 0 or 1, R is a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a tetrazolyl group, a halogen atom, a cyano group, a nitro group, a C alkyl group, a C 1-3 1-3 haloalkyl group, a C cycloalkyl group, a C alkoxy group, a C haloalkoxy group or 3-6 1-3 1-3 a C alkylsulfonyl group, L is a single bond, and R is a hydrogen atom, a halogen atom, a C cycloalkyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (9) The compound according to (7), wherein the ring B is a C cycloalkane, a 4 to 3-11 7-membered non-aromatic heterocycle or benzene, n is, 0 or 1, and R is a hydroxy group, a halogen atom, a cyano group or a C alkyl group, a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (10) The compound according to (7) or (9), wherein L is a single bond, a C alkylene group, a C alkenylene group or a C haloalkylene group (the C alkylene group, the 2-6 1-6 1-6 C alkenylene group and the C haloalkylene group are unsubstituted or substituted 2-6 1-6 40 with one or two identical or different substituents independently selected from the group consisting of hydroxy groups and cyano groups), the ring B is a C cycloalkane or a 4 to 7-membered non-aromatic heterocycle, and 3-11 R is a hydrogen atom, a halogen atom, a C cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 10-membered aromatic 45 heterocyclyl group (the C cycloalkyl group, the 3 to 11-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 10-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of hydroxy groups, amino groups, halogen atoms, cyano groups, nitro groups, carboxy groups, carbamoyl groups, sulfamoyl groups, C alkyl groups, C alkoxy groups, mono-C alkylamino groups, 1-6 1-6 1-6 di-C alkylamino groups, C alkylthio groups, C alkylcarbonyl groups, C 1-6 1-6 1-6 1-6 alkylsulfonyl groups, C alkoxycarbonyl groups, mono-C alkylaminocarbonyl groups, 1-6 1-6 di-C alkylaminocarbonyl groups, C alkylcarbonylamino groups (the C alkyl groups, 1-6 1-6 1-6 the C alkoxy groups, the mono-C alkylamino groups, the di-C alkylamino groups, 1-6 1-6 1-6 the C alkylthio groups, the C alkylcarbonyl groups, the C alkylsulfonyl groups, the 1-6 1-6 1-6 C alkoxycarbonyl groups, the mono-C alkylaminocarbonyl groups, the di-C 1-6 1-6 1-6 alkylaminocarbonyl groups and the C alkylcarbonylamino groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, amino groups, cyano groups and C alkoxy groups), C cycloalkyl groups, 4 to 7-membered non-aromatic 1-3 3-6 heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups (the C cycloalkyl groups, the 4 to 7-membered non-aromatic heterocyclyl groups, the phenyl groups and the 5 to 6-membered aromatic heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of hydroxy groups, halogen atoms, cyano groups, C alkyl groups and C haloalkyl groups)), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (11) The compound according to (7) or (9), wherein L is a single bond, a C alkylene group, a C alkenylene group (the C alkylene group and the C alkenylene group 2-3 1-3 2-3 are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups and cyano groups) or a C haloalkylene group, and R is a hydrogen atom or a halogen atom, a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (12) The compound according to any one of (7), (9) and (10), wherein the ring B is a C cycloalkane or a 4 to 7-membered non-aromatic heterocycle, and R is a 3 to 11-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to -membered aromatic heterocyclyl group (the 3 to 11-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 10-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of hydroxy groups, halogen atoms, cyano groups, carbamoyl groups, C alkyl groups, C alkoxy groups, 1-3 1-3 mono-C alkylamino groups, di-C alkylamino groups (the C alkyl groups, the C 1-3 1-3 1-3 1-3 alkoxy groups, the mono-C alkylamino groups and the di-C alkylamino groups are 1-3 1-3 unsubstituted or substituted with a hydroxy group or a cyano group), C haloalkyl groups, C haloalkoxy groups, C alkylthio groups, C haloalkylthio groups, C 1-3 1-3 1-3 1-3 40 alkylsulfonyl groups, C haloalkylsulfonyl groups, 4 to 7-membered non-aromatic heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups (the 4 to 7-membered non-aromatic heterocyclyl groups, the phenyl groups and the 5 to 6-membered aromatic heterocyclyl groups are unsubstituted or substituted with a substituent selected from the group consisting of a halogen atom, a C alkyl group and 45 a C haloalkyl group)), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (13) The compound according to any one of (7), (9) and (10), wherein the ring B is a C cycloalkane, and R is a 4 to 7-membered non-aromatic heterocyclyl group (the 4 to 7-membered non- aromatic heterocyclyl group is unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, halogen atoms, cyano groups, carboxy groups, C alkyl groups (the C alkyl 1-3 1-3 groups are unsubstituted or substituted with a hydroxy group or a cyano group), C haloalkyl groups, C alkoxy groups, di-C alkylamino groups, mono-C 1-3 1-3 1-3 alkylaminocarbonyl groups, C alkylsulfonyl group, C alkylcarbonylamino groups (the 1-3 1-3 C alkoxy groups, the di-C alkylamino groups, the mono-C alkylaminocarbonyl 1-3 1-3 1-3 groups, the C alkylsulfonyl group and the C alkylcarbonylamino groups are 1-3 1-3 unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms), 4 to 7-membered non-aromatic heterocyclyl groups and phenyl groups (the phenyl groups are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms, C alkyl groups and C haloalkyl groups)), a tautomer or a 1-3 1-3 pharmaceutically acceptable salt of the compound or a solvate thereof. (14) The compound according to any one of (2) to (6), wherein L is a single bond, L is a single bond, a C alkylene group or a C alkenylene group (the C alkylene 1-6 2-6 1-6 group and the C alkenylene group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, amino groups, cyano groups and nitro groups), the ring B is a C cycloalkane, a C cycloalkene, a 3 to 11-membered non-aromatic 3-11 3-11 heterocycle, a C aromatic carbocycle or a 5 to 10-membered aromatic heterocycle, 6-14 n is 0 or 1, R is a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a halogen atom, a cyano group, a C alkyl group, a C haloalkyl group, a C cycloalkyl group, a 1-3 1-3 3-6 C alkoxy group, a C haloalkoxy group or a C alkylsulfonyl group, 1-3 1-3 1-3 3a a a L is represented by any of the following formulae (XIV -1) to (XIV -15): R 12a 1a O a a a a a (XIV -1 ) (XIV -2 ) ( XIV -3 ) ( XIV -4 ) (XIV -5 ) 1a 1a (XIV ) N N O 12a 13a R 12a 12a 13a a a a a a (XIV -6 ) ( XIV -7 ) ( XIV -8 ) (XIV -9 ) ( XIV -10 ) O N O R 12a a a a a a ( XIV -11 ) ( XIV -12 ) (XIV -13 ) ( XIV -14 ) ( XIV -15 ) 1a 11a 11a (wherein E is an oxygen atom, a sulfur atom or NR (wherein R is a hydroxy group 12a 13a or a C alkoxy group), each of R and R is independently a hydrogen atom, a C 1-3 1-6 alkyl group or a C haloalkyl group (the C alkyl group and the C haloalkyl group 1-6 1-6 1-6 are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of hydroxy groups, amino groups, cyano groups, C cycloalkyl groups, C alkoxy groups, C haloalkoxy groups, C 3-11 1-6 1-6 1-6 alkylthio groups, C alkylsulfonyl groups, C haloalkylsulfonyl groups, C 1-6 1-6 1-6 alkoxycarbonyl groups, 3 to 11-membered non-aromatic heterocyclyl groups, mono-C alkylamino groups, di-C alkylamino groups, mono-C alkylaminocarbonyl groups, di- 1-6 1-6 C alkylaminocarbonyl groups, C alkylcarbonylamino groups, phenyl groups and 5 to 1-6 1-6 -membered aromatic heterocyclyl groups (the phenyl groups and the 5 to 10- membered aromatic heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ))), and R is a hydrogen atom, a C alkyl group, a C alkenyl group (the C alkyl group and 1-6 2-6 1-6 the C alkenyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a C 3-11 cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a phenyl group, a naphthyl group or a 5 to 10-membered aromatic heterocyclyl group (the C 3-11 cycloalkyl group, the 3 to 11-membered non-aromatic heterocyclyl group, the phenyl group, the naphthyl group and the 5 to 10-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (15) The compound according to any one of (2) to (6), wherein L is a single bond or a C alkylene group, L is a single bond or a C alkylene group (the C alkylene group is unsubstituted or 1-3 1-3 substituted with a cyano group or a C haloalkyl group), the ring B is a C cycloalkane, a C cycloalkene, a 3 to 11-membered non-aromatic 3-11 3-11 heterocycle, benzene or a 5 to 6-membered aromatic heterocycle, n is 0 or 1 R is a hydroxy group, an amino group, a carbamoyl group, a halogen atom, a cyano group, a C alkyl group, a C haloalkyl group, a C cycloalkyl group, a C alkoxy 1-3 1-3 3-6 1-3 group, a C haloalkoxy group or a C alkylsulfonyl group, 1-3 1-3 3a a a L is represented by any of the following formulae (V -1) to (V -11): R 12a E E O O a a a a a ( V -1 ) ( V -2 ) ( V -3 ) ( V -4 ) ( V -5 ) ( V -6 ) (V ) 12a 13a 12a 13a a a a a a ( V -7 ) ( V -8 ) ( V -9 ) ( V -10 ) ( V -11 ) 1a 12a 13a (wherein E is an oxygen atom, each of R and R is independently a hydrogen atom, a C alkyl group or a C haloalkyl group), and 1-6 1-6 R is a hydrogen atom, a C alkyl group (the C alkyl group is unsubstituted or 1-6 1-6 substituted with one or more identical or different substituents independently selected from the substituent set V ), a C cycloalkyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (16) The compound according to (14), wherein L is a single bond, a C alkylene group, a C alkenylene group (the C alkylene group and the C alkenylene group 2-3 1-3 2-3 are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups and cyano groups) or a C haloalkylene group, the ring B is a C cycloalkane, a 4 to 7-membered non-aromatic heterocycle or 3-11 benzene, n is 0 or 1, R is a halogen atom, a cyano group or a C alkyl group, and 3a a a L is represented by any of the following formulae (XV -1) to (XV -12): R 1a 1a O E O O a a a ( XV -6 ) ( XV -1 ) ( XV -2 ) ( XV -3 ) (XV -4 ) (XV -5 ) ( XV ) 1a 1a O N S N O N 12a 12a 12a a a a a a a (XV -7 ) (XV -8 ) ( XV -9 ) ( XV -10 ) ( XV -11 ) ( XV -12 ) 1a 11a 11a 12a (wherein E is an oxygen atom or NR (wherein R is a hydroxy group), and R is a hydrogen atom, a C alkyl group or a C haloalkyl group (the C alkyl group and 1-6 1-6 1-6 the C haloalkyl group is unsubstituted or substituted with a substituent selected from the group consisting of a hydroxy group, a cyano group, a C alkoxy group, a C 1-3 3-6 cycloalkyl group, a phenyl group and a 5 to 6-membered aromatic heterocyclyl group (the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with a substituent selected from the group consisting of a halogen atom, a cyano group, a C alkyl group and a C haloalkyl group))), a 1-3 1-3 tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (17) The compound according to (14) or (16), wherein L is a single bond or a C alkylene group, the ring B is a C cycloalkane or a 4 to 7-membered non-aromatic heterocycle, and R is a hydrogen atom, a C alkyl group, a C haloalkyl group (the C alkyl group 1-6 1-6 1-6 and the C haloalkyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of cyano groups, hydroxy groups, C alkoxy groups, mono-C alkylaminocarbonyl groups, di- 1-6 1-6 C alkylaminocarbonyl groups (the mono-C alkylaminocarbonyl groups and the di- 1-6 1-6 C alkylaminocarbonyl groups are unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms), C cycloalkyl groups, 4 to 7-membered non-aromatic heterocyclyl groups, phenyl groups or 5 to 10- membered aromatic heterocyclyl groups (the C cycloalkyl groups, the 4 to 7- membered non-aromatic heterocyclyl groups, the phenyl groups and the 5 to 10- membered aromatic heterocyclyl groups are unsubstituted or substituted with identical or different one , two or three substituents independently selected from the group consisting of hydroxy groups, halogen atoms, cyano groups, C alkoxy groups, C 1-6 1-6 haloalkoxy groups, C alkylthio groups, C haloalkylthio groups, C alkylsulfonyl 1-6 1-6 1-6 groups, C haloalkylsulfonyl groups, C alkoxycarbonyl groups, 4 to 7-membered 1-6 1-6 non-aromatic heterocyclyl groups and phenyl groups (the phenyl groups are unsubstituted or substituted with a halogen atom))), a C cycloalkyl group, a 4 to 7- 3-11 membered non-aromatic heterocyclyl group, a phenyl group, a naphthyl group or a 5 to -membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7- 3-11 membered non-aromatic heterocyclyl group, the phenyl group, the naphthyl group and the 5 to 10-membered aromatic heterocyclyl group are unsubstituted or substituted with one, two or three identical or different substituents independently selected from the group consisting of hydroxy groups, halogen atoms, cyano groups, C alkyl groups (the C alkyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, cyano groups, hydroxy groups and C alkoxy groups), C alkoxy groups, C 1-3 1-6 1-6 haloalkoxy groups, C alkylthio groups, C haloalkylthio groups, C alkylsulfonyl 1-6 1-6 1-6 groups, C haloalkylsulfonyl groups, C alkoxycarbonyl groups (the C 1-6 1-6 1-6 alkoxycarbonyl groups are unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms), 4 to 7-membered non- aromatic heterocyclyl groups and phenyl groups (the phenyl groups are unsubstituted or substituted with a halogen atom)), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (18) The compound according to any one of (14), (16) and (17), wherein L is represented by any of the following formulae (XXIII -1) to (XXIII -7): 1a 12a (wherein E is an oxygen atom, and R is a hydrogen atom, a C alkyl group (the C 1-3 1- alkyl group is unsubstituted or substituted with a cyano group) or a C haloalkyl 3 1-3 group), and R is a C alkyl group (the C alkyl group is unsubstituted or substituted with a cyano 1-6 1-6 group), a C haloalkyl group, a C cycloalkyl group, a 4 to 7-membered non-aromatic 1-6 3-6 heterocyclyl group or a phenyl group (the 4 to 7-membered non-aromatic heterocyclyl group and the phenyl group are unsubstituted or substituted with a substituent selected from the group consisting of a halogen atom, a hydroxy group, a cyano group, a C alkyl group and a C haloalkyl group), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (19) The compound according to any one of (14) and (16) to (18), wherein L is represented by any of the following formulae (XXIV -1) to (XXIV -4): 1a 12a (wherein E is an oxygen atom, and R is a hydrogen atom, a C alkyl group (the C 1-3 1- alkyl group is unsubstituted or substituted with a cyano group) or a C haloalkyl 3 1-3 group), and R is a C alkyl group (the C alkyl group is unsubstituted or substituted with a cyano 1-3 1-3 group), a C haloalkyl group or a C cycloalkyl group, a tautomer or a 1-3 3-6 pharmaceutically acceptable salt of the compound or a solvate thereof. (20) The compound according to any one of (14), (16) and (17), wherein L is represented by the formula (XVI ): (XVI ) (wherein R is a hydrogen atom, a C alkyl group (the C alkyl group is 1-3 1-3 unsubstituted or substituted with a substituent selected from the group consisting of a hydroxy group, a cyano group, a C alkoxy group, a C cycloalkyl group and a phenyl 1-3 3-6 group) or a C haloalkyl group), and R is a hydrogen atom, a C alkyl group (the C alkyl group is unsubstituted or 1-6 1-6 substituted with one or two identical or different substituents independently selected from the group consisting of cyano groups, hydroxy groups, C alkoxy groups, mono- C alkylaminocarbonyl groups (the mono-C alkylaminocarbonyl groups are 1-3 1-3 unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms), C cycloalkyl groups, 4 to 7-membered non- aromatic heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups (the C cycloalkyl groups, the 4 to 7-membered non-aromatic heterocyclyl groups, the phenyl groups and the 5 to 6-membered aromatic heterocyclyl groups are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, halogen atoms, cyano groups, C alkoxy groups, C haloalkoxy groups, C alkylsulfonyl groups, C 1-3 1-3 1-3 1-6 alkoxy carbonyl groups and phenyl groups (the phenyl groups are unsubstituted or substituted with a halogen atom))), a C haloalkyl group (the C haloalkyl group is 1-6 1-6 unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups (the phenyl groups and the 5 to 6- membered aromatic heterocyclyl groups are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms, C alkoxy groups and C alkylthio groups)), a C cycloalkyl group, 1-3 1-3 3-11 a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 10- membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered 3-11 non-aromatic heterocyclyl group, the phenyl group and the 5 to 10-membered aromatic heterocyclyl group are unsubstituted or substituted with one, two or three identical or different substituents independently selected from the group consisting of hydroxy groups, halogen atoms, cyano groups, C alkyl groups (the C alkyl groups are 1-3 1-3 unsubstituted or substituted with a substituent selected from the group consisting of a hydroxy group, a cyano group and a C alkoxy group), C haloalkyl groups, C 1-3 1-3 1-3 alkoxy groups, C haloalkoxy groups, C alkylsulfonyl groups, C haloalkylsulfonyl 1-3 1-3 1-3 groups, C alkoxycarbonyl groups, 4 to 7-membered non-aromatic heterocyclyl groups and phenyl groups (the phenyl groups are unsubstituted or substituted with a halogen atom)), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (21) The compound according to any one of (2) to (12) and (14) to (19), wherein the ring B is cyclohexane or piperidine, a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (22) The compound according to (13) or (20), wherein the ring B is cyclohexane, a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. a 9a (23) The compound according to any one of (5) to (22), wherein X is CR (wherein R is a hydrogen atom), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (24) The compound according to any one of (6) to (23), wherein the ring A is represented by any of the following formulae (IV -1) to (IV -3): 4a a ( IV ) a a a ( IV -1 ) ( IV -2 ) (IV -3 ) 2a 4a 6a (wherein E is an oxygen atom or a sulfur atom, and each of R and R is independently a hydrogen atom or a C alkyl group), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (25) The compound according to any one of (8), (23) and (24), wherein L is a single bond, L is a single bond or a C alkylene group, the ring B is a C cycloalkane, benzene or a 4 to 7-membered non-aromatic 40 heterocycle, n is 0, L is a single bond, and R is a hydrogen atom, a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (26) The compound according to any one of (15), (23) and (24), wherein L is a single bond, L is a single bond, the ring B is a C cycloalkane or a 4 to 7-membered non-aromatic heterocycle, n is 0, 3a a a L is represented by any of the following formulae (VI -1) to (VI -3): ( VI ) ( VI -3) (VI -1) (VI -2) , and R is a hydrogen atom or a C alkyl group (the C alkyl group is unsubstituted or 1-3 1-3 substituted with a cyano group or a phenyl group), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (27) The compound according to any one of (2) to (6), (8), (15), (25) and (26), wherein the ring B is cyclohexane, benzene or piperidine, a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (28) The compound according to (1), wherein R is a hydrogen atom, a 9a 9a X is CR (wherein R is a hydrogen atom or a halogen atom), a 10a 10a Y is CR (wherein R is a hydrogen atom), a a a the ring A is represented by any of the following formulae (IV -1) to (IV -3): ( IV ) a a a ( IV -1 ) ( IV -2 ) ( IV -3 ) 2a 4a (wherein E is an oxygen atom or a sulfur atom, R is a hydrogen atom or a C alkyl group, and R is a hydrogen atom), L is a single bond, the ring B is a C cycloalkane, a C cycloalkene (a ring-constituting methylene 3-11 3-11 group of the C cycloalkane and the C cycloalkene may be replaced by a carbonyl 3-11 3-11 group), a 3 to 11-membered non-aromatic heterocycle, a C aromatic carbocycle or a 6-14 to 10-membered aromatic heterocycle, n is 0, 1 or 2, R is a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a halogen atom, a cyano group, a C alkyl group, a C haloalkyl group or a C alkoxy group 1-3 1-3 1-3 a 3a (when n is 2, R ’s may be identical or different), L is a single bond, a C alkylene group, a C alkenylene group (the C alkylene 1-6 2-6 1-6 group and the C alkenylene group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, amino groups, cyano groups and nitro groups), 15a 15a =C(R )- (wherein R is a hydrogen atom or a cyano group, and the bond connecting a 2a 15a 15a the ring B and L is a double bond) or =C(R )-CH - (wherein R is a hydrogen atom a 2a or a cyano group, and the bond connecting the ring B and L is a double bond), 3a a a L is a single bond or represented by any of the following formulae (XIV -1) to (XIV -15) and (XIII ) (wherein E is an oxygen atom), 3a 2a when L is a single bond, R is a hydrogen atom, a halogen atom, an azido group, a C cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a C aryl 3-11 6-14 group, a 5 to 10-membered aromatic heterocyclyl group, a 8 to 11-membered partially saturated aromatic cyclic group or a 8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon group (the C cycloalkyl group, the 3 to 11-membered non- 3-11 aromatic heterocyclyl group, the C aryl group, the 5 to 10-membered aromatic 6-14 heterocyclyl group, the 8 to 11-membered partially saturated aromatic cyclic group and the 8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon groupg are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of the substituent set V , the substituent set V and C alkyl groups (the C alkyl groups are substituted with a C 1-6 1-6 1-6 alkoxycarbonylamino group (the C alkoxycarbonylamino group is unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms))), 3a 2a when L is not a single bond, R is a hydrogen atom, a C alkyl group, a C alkenyl 1-6 2-6 group, a C alkynyl group (the C alkyl group, the C alkenyl group and the C 2-6 1-6 2-6 2-6 alkynyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V and the substituent set V ), a C cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a 3-11 C aryl group, a 5 to 10-membered aromatic heterocyclyl group, a 8 to 11-membered 6-14 partially saturated aromatic cyclic group or a 8 to 11-membered aromatic ring- condensed alicyclic hydrocarbon group (the C cycloalkyl group, the 3 to 11- 3-11 membered non-aromatic heterocyclyl group, the C aryl group, the 5 to 10-membered 6-14 aromatic heterocyclyl group, the 8 to 11-membered partially saturated aromatic cyclic group and the 8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon group are unsubstituted or substituted with one or more identical or different substituents 4a 9a independently selected from the substituent set V and the substituent set V ), and 12a 13a each of R and R is independently a hydrogen atom, a C alkyl group, a C 1-6 1-6 haloalkyl group (the C alkyl group and the C haloalkyl group are unsubstituted or 1-6 1-6 substituted with one or more identical or different substituents independently selected 2a 8a 9a from the substituent set V , the substituent set V and the substituent set V ), a C 3-11 cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a C aryl 6-14 group, a 5 to 10-membered aromatic heterocyclyl group or a 8 to 11-membered partially saturated aromatic cyclic group (the C cycloalkyl group, the 3 to 11-membered non- 3-11 aromatic heterocyclyl group, the C aryl group, the 5 to 10-membered aromatic 6-14 heterocyclyl group and the 8 to 11-membered partially saturated aromatic cyclic group are unsubstituted or substituted with one or more identical or different substituents 4a 9a independently selected from the substituent set V and the substituent set V ), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (29) The compound according to (1) or (28), wherein L is a single bond, a C alkylene group, a C alkenylene group (the C alkylene group and the C alkenylene 2-6 1-6 2-6 group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups and cyano groups) or a C haloalkylene group, the ring B is a C cycloalkane (a ring-constituting methylene group of the C 4-7 4-7 cycloalkane may be replaced by a carbonyl group) or a 4 to 7-membered non-aromatic heterocycle, n is 0, 1 or 2, 3a a 3a R is a cyano group, a C alkyl group or a halogen atom (when n is 2, R ’s may be identical or different), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (30) The compound according to any one of (1), (28) and (29), wherein L is a single bond, R is a hydrogen atom, a halogen atom, an azido group, a C cycloalkyl group, a 3 to 3-11 11-membered non-aromatic heterocyclyl group, a phenyl group, a 5 to 10-membered 40 aromatic heterocyclyl group or a 8 to 11-membered partially saturated aromatic cyclic group (the C cycloalkyl group, the 3 to 11-membered non-aromatic heterocyclyl 3-11 group, the phenyl group, the 5 to 10-membered aromatic heterocyclyl group and the 8 to 11-membered partially saturated aromatic cyclic group are unsubstituted or substituted with one or more identical or different substituents independently selected 4a 9a 45 from the group consisting of the substituent set V , the substituent set V and C alkyl groups (the C alkyl groups are substituted with a C alkoxycarbonylamino group (the 1-6 1-6 C alkoxycarbonylamino group is unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms))), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (31) The compound according to (30), wherein L is a C alkylene group, the ring B is a 4 to 7-membered non-aromatic heterocycle, L is a single bond, R is a phenyl group or a 5 to 10-membered aromatic heterocyclyl group or a 8 to 11- membered partially saturated aromatic cyclic group (the phenyl group, the 5 to 10- membered aromatic heterocyclyl group and the 8 to 11-membered partially saturated aromatic cyclic group are unsubstituted or substituted with one, two or three identical or different substituents independently selected from the group consisting of hydroxy groups, halogen atoms, cyano groups, carbamoyl groups, C alkyl groups, C 1-6 1-6 haloalkyl groups, C alkoxy groups, C haloalkoxy groups, di-C alkylamino groups, 1-6 1-6 1-6 C alkylthio groups, C haloalkylthio groups, C alkylsulfonyl groups, 4 to 7- 1-6 1-6 1-6 membered non-aromatic heterocyclyl groups and 5 to 6-membered aromatic heterocyclyl groups), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (32) The compound according to any one of (28) to (30), wherein the ring B is a C cycloalkane, L is a single bond, R is a 3 to 11-membered non-aromatic heterocyclyl group (the 3 to 11-membered non- aromatic heterocyclyl group is unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of hydroxy groups, amino groups, halogen atoms, cyano groups, carbamoyl groups, carboxy groups, C alkyl groups (the C alkyl groups are unsubstituted or substituted with one 1-6 1-6 or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms or with a substituent selected from the group consisting of a hydroxy group, a cyano group and a C alkoxycarbonylamino group), C alkoxy groups, mono-C alkylaminocarbonyl 1-6 1-3 1-3 groups, C alkylcarbonylamino groups (the C alkoxy groups, the mono-C 1-3 1-3 1-3 alkylaminocarbonyl groups, the C alkylcarbonylamino groups are unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms), di-C alkylamino groups, C alkylsulfonyl groups, di-C alkylaminosulfonyl 1-3 1-3 1-3 groups, C alkoxycarbonylamino groups, 4 to 7-membered non-aromatic heterocyclyl groups and phenyl groups (the phenyl groups are unsubstituted or substituted with a halogen atom)), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (33) The compound according to any one of (1), (28) and (29), wherein L is a a a 40 represented by any of the following formulae (XV -1) to (XV -12) and (XIII ): R 12a R 1a 1a O E 1a a a a a a ( XV -6 ) ( XV -1 ) ( XV -2 ) ( XV -3 ) (XV -4 ) (XV -5 ) ( XV ) O N S N O N 12a 12a a a a a a a (XV -7 ) (XV -8 ) ( XV -9 ) ( XV -10 ) ( XV -11 ) ( XV -12 ) 1a 12a (wherein E is an oxygen atom, and R is a hydrogen atom, a C alkyl group (the C 1-6 1- alkyl group is unsubstituted or substituted with a substituent selected from the group consisting of a hydroxy group, a cyano group, a C alkoxy group, a C cycloalkyl 1-3 3-6 group, a phenyl group and a 5 to 6-membered aromatic heterocyclyl group (the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with a substituent selected from the group consisting of a halogen atom, a cyano group, a C alkyl group and a C haloalkyl group)), a C haloalkyl group, a C 1-3 1-3 1-6 3- cycloalkyl group or a phenyl group (the phenyl group is unsubstituted or substituted with a halogen atom or a cyano group)), R is a hydrogen atom, a C alkyl group (the C alkyl group is unsubstituted or 1-6 1-6 substituted with one or more identical or different substituents independently selected 6a 9a from the substituent set V and the substituent set V ), a C alkynyl group, a C 2-6 3-11 cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a phenyl group, a 5 to 10-membered aromatic heterocyclyl group, a 8 to 11-membered partially saturated aromatic cyclic group or a 8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon group (the C cycloalkyl group, the 3 to 11-membered non- 3-11 aromatic heterocyclyl group, the phenyl group, the 5 to 10-membered aromatic heterocyclyl group, the 8 to 11-membered partially saturated aromatic cyclic group and the 8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon group are unsubstituted or substituted with one or more identical or different substituents 4a 9a independently selected from the substituent set V and the substituent set V ), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (34) The compound according to (33), wherein the ring B is a C cycloalkane or a 4 to 7-membered non-aromatic heterocycle, 3a a a L is represented by the following formulae (XXV -1) or (XXV -2): (wherein R is a hydrogen atom, a C alkyl group (the C alkyl group is 1-3 1-3 unsubstituted or substituted with a substituent selected from the group consisting of a hydroxy group, a cyano group, a C alkoxy group, a C cycloalkyl group and a phenyl 1-3 3-6 group), a C haloalkyl group, a C cycloalkyl group or a phenyl group (the phenyl 1-3 3-6 group is unsubstituted or substituted with a halogen atom or a cyano group)), R is a hydrogen atom, a C alkyl group, a C haloalkyl group (the C alkyl group 1-6 1-6 1-6 and the C haloalkyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, cyano groups, C alkoxy groups, C alkylthio groups, C alkylsulfonyl groups, 1-3 1-3 1-3 mono-C alkylaminocarbonyl groups, di-C alkylaminocarbonyl groups (the mono-C 1-3 1-3 1-3 alkylaminocarbonyl groups and the di-C alkylaminocarbonyl groups are unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms), C cycloalkyl groups, 4 to 7-membered non-aromatic heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups (the C cycloalkyl groups, the 4 to 7-membered non-aromatic heterocyclyl groups, the phenyl groups and the 5 to 6-membered aromatic heterocyclyl groups are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, amino groups, halogen atoms, cyano groups, C alkyl groups, C haloalkyl groups, C alkoxy groups, C haloalkoxy 1-3 1-3 1-3 1-3 groups, C alkylthio groups, C haloalkylthio groups, C alkylsulfonyl groups, C 1-3 1-3 1-3 1-3 haloalkylsulfonyl groups, C alkoxycarbonyl groups, mono-C alkylamino groups, di- 1-6 1-3 C alkylamino groups, mono-C alkylaminocarbonyl groups, di-C 1-3 1-3 1-3 alkylaminocarbonyl groups, C alkylcarbonylamino group (the C alkoxycarbonyl 1-3 1-6 groups, the mono-C alkylamino groups, the di-C alkylamino groups, the mono-C 1-3 1-3 1-3 alkylaminocarbonyl groups, the di-C alkylaminocarbonyl groups and the C 1-3 1-3 alkylcarbonylamino group are unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms), 4 to 7-membered non- aromatic heterocyclyl groups, phenyl groups (the phenyl groups are unsubstituted or substituted with a halogen atom) and 5 to 6-membered aromatic heterocyclyl groups)), a C alkynyl group, a C cycloalkyl group, a 4 to 7-membered non-aromatic 2-6 3-6 heterocyclyl group, a phenyl group, a 8 to 11-membered partially saturated aromatic cyclic group or a 8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon group (the C cycloalkyl group, the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group, the 8 to 11-membered partially saturated aromatic cyclic group and the 8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon group are unsubstituted or substituted with one, two or three identical or different substituents independently selected from the group consisting of hydroxy groups, amino groups, 40 halogen atoms, cyano groups, C alkyl groups (the C alkyl groups are unsubstituted 1-3 1-3 or substituted with a substituent selected from the group consisting of a hydroxy group, a cyano group and a C alkoxy group), C haloalkyl groups, C alkoxy groups, C 1-3 1-3 1-3 1-3 haloalkoxy groups, C alkylthio groups, C haloalkylthio groups, C alkylsulfonyl 1-3 1-3 1-3 groups, C haloalkylsulfonyl groups, C alkoxycarbonyl groups, mono-C alkylamino 1-3 1-6 1-3 45 groups, di-C alkylamino groups, mono-C alkylaminocarbonyl groups, di-C 1-3 1-3 1-3 alkylaminocarbonyl groups, C alkylcarbonylamino groups (the C alkoxycarbonyl 1-3 1-6 groups, the mono-C alkylamino groups, the di-C alkylamino groups, the mono-C 1-3 1-3 1-3 alkylaminocarbonyl groups, the di-C alkylaminocarbonyl groups and the C 1-3 1-3 alkylcarbonylamino group are unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms), 4 to 7-membered non- aromatic heterocyclyl groups and phenyl groups (the phenyl groups are unsubstituted or substituted with a halogen atom)), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (35) The compound according to (33), wherein the ring B is a C cycloalkane, 3a a a L is represented by any of the following formulae (XXVI -1) to (XXVI -5): 1a 12a (wherein E is an oxygen atom, and R is a hydrogen atom, a C alkyl group (the C 1-3 1- alkyl group is unsubstituted or substituted with a substituent selected from the group consisting of a hydroxy group, a cyano group, a C alkoxy group, a C cycloalkyl 1-3 3-6 group, a phenyl group and a 5 to 6-membered aromatic heterocyclyl group (the 5 to 6- membered aromatic heterocyclyl group is unsubstituted or substituted with a C alkyl group)), a C haloalkyl group, a C cycloalkyl group or a phenyl group (the 1-3 1-3 3-6 phenyl group is unsubstituted or substituted with a halogen atom or a cyano group)), R is a C alkyl group (the C alkyl group is unsubstituted or substituted with a cyano 1-3 1-3 group), a C haloalkyl group or a C cycloalkyl group, a tautomer or a 1-3 3-6 pharmaceutically acceptable salt of the compound or a solvate thereof. (36) The compound according to (34) or (35), wherein L is represented by the formula (XVI ): N (XVI ) (wherein R is a hydrogen atom, a C alkyl group (the C alkyl group is 1-3 1-3 unsubstituted or substituted with a substituent selected from the group consisting of a hydroxy group, a cyano group, a C alkoxy group, a C cycloalkyl group and a phenyl 1-3 3-6 group), a C haloalkyl group, a C cycloalkyl group or a phenyl group (the phenyl 1-3 3-6 group is unsubstituted or substituted with a halogen atom or a cyano group)), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. 3a a (37) The compound according to (33), wherein L is represented by the formula (XIII ): (wherein E is an oxygen atom), R is a C alkyl group, a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (38) The compound according to any one of (1) to (24), (28) to (30) and (32) to (37), wherein L is a single bond or a C alkylene group, a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (39) The compound according to (1) or (28), wherein L is a single bond, the ring B is a C cycloalkane, 2a 15a 15a L is =C(R )- (wherein R is a hydrogen atom or a cyano group, and the bond a 2a 15a 15a connecting the ring B and L is a double bond) or =C(R )-CH - (wherein R is a a 2a hydrogen atom or a cyano group, and the bond connecting the ring B and L is a double bond), and 3a 2a when L is a single bond, R is a hydrogen atom, and 3a a when L is the formula (X -2): ( X -2) R is a C alkyl group, a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (40) The compound according to any one of (1) to (39), wherein n is 0, a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof.

The invention provides the following aspects: (41) A compound represented by the formula (I ): (R ) b ( I ) 1b N [wherein the ring A is represented by the formula (II ): (II ) 1b 4b 5b 17b 1b (wherein T is CR R , C(=O), C(=S), C(=NR ), a sulfur atom, S(=O) or S(=O) , U 6b 1b 8b b is a nitrogen atom or CR , and W is a nitrogen atom or CR ), the formula (III ): (III ) 2b 4b 2b 6b 2b 8b 9b (wherein T is CR , U is a nitrogen atom or CR , and W is CR R , C(=O), C(=S), 17b 10b C(=NR ), NR , an oxygen atom, a sulfur atom, S(=O) or S(=O) (provided that when 2b 6b 2b b U is CR , W is not C(=O))) or the formula (IV ): 3b (IV ) 3b 4b 5b 17b 3b (wherein T is CR R , C(=O), C(=S), C(=NR ), a sulfur atom, S(=O) or S(=O) , U 6b 7b 17b 10b is CR R , C(=O), C(=S), C(=NR ), NR , an oxygen atom, a sulfur atom, S(=O) or 3b 8b 9b 17b 11b S(=O) , and W is CR R , C(=O), C(=S), C(=NR ), NR , an oxygen atom, a sulfur 3b 4b 5b 3b 6b 7b 3b atom, S(=O) or S(=O) (provided that when T is CR R and U is CR R , W is 8b 9b not CR R )), b 15b X is a nitrogen atom or CR , b 16b Y is CR , R is a hydrogen atom, a halogen atom, a C alkyl group or a C haloalkyl group, 1-6 1-6 the ring B is a C cycloalkane, a C cycloalkene, a 3 to 11-membered non-aromatic 3-11 3-11 heterocycle, a C aromatic carbocycle or a 5 to 10-membered aromatic heterocycle, 6-14 L is a single bond, a C alkylene group, a C alkenylene group or a C alkynylene 1-6 2-6 2-6 group (the C alkylene group, the C alkenylene group and the C alkynylene group 1-6 2-6 2-6 are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, amino groups, cyano groups and nitro groups), L is a single bond, a C alkylene group, a C alkenylene group or a C alkynylene 1-6 2-6 2-6 group (the C alkylene group, the C alkenylene group and the C alkynylene group 1-6 2-6 2-6 are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, amino groups, cyano groups and nitro groups), 3b b b L is a single bond or represented by any of the following formulae (V -1) to (V -20): O S S 12b 1b b b R E ( V -1 ) ( V -2 ) b b b b (V -3 ) (V -4 ) ( V -5 ) ( V -6 ) 1b 13b b b b b b ( V -7 ) (V -8 ) (V -9 ) (V -10 ) ( V -11 ) ( V ) 1b 1b O N N N 12b 12b 13b R R R b b b b b (V -12 ) (V -13 ) ( V -14 ) ( V -15 ) (V -16 ) 1b 1b 14b E E R O N N N N N 12b 12b 13b 12b 13b R R R R R b b b b (V -17 ) ( V -18 ) (V -19 ) (V -20 ) 1b 18b (wherein E is an oxygen atom, a sulfur atom or NR ), 3b 2b when L is a single bond, R is a hydrogen atom, a halogen atom, a C cycloalkyl 3-11 group, a 3 to 14-membered non-aromatic heterocyclyl group, a C aryl group, a 5 to 6-14 10-membered aromatic heterocyclyl group, a 8 to 14-membered partially saturated aromatic cyclic group or a 8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon group (the C cycloalkyl group, the 3 to 14-membered non-aromatic 3-11 heterocyclyl group, the C aryl group, the 5 to 10-membered aromatic heterocyclyl 6-14 group, the 8 to 14-membered partially saturated aromatic cyclic group and the 8 to 14- membered aromatic ring-condensed alicyclic hydrocarbon group are unsubstituted or substituted with one or more identical or different substituents independently selected 4b 9b from the substituent set V and the substituent set V ), 3b 2b when L is not a single bond, R is a hydrogen atom, a C alkyl group, a C alkenyl 1-6 2-6 group (the C alkyl group and the C alkenyl group are unsubstituted or substituted 1-6 2-6 with one or more identical or different substituents independently selected from the 6b 9b substituent set V and the substituent set V ), a C cycloalkyl group, a 3 to 14- 3-11 membered non-aromatic heterocyclyl group, a C aryl group, a 5 to 10-membered 6-14 aromatic heterocyclyl group, a 8 to 14-membered partially saturated aromatic cyclic group or a 8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon group (the C cycloalkyl group, the 3 to 14-membered non-aromatic heterocyclyl group, the C 3-11 6-14 aryl group, the 5 to 10-membered aromatic heterocyclyl group, the 8 to 14-membered partially saturated aromatic cyclic group and the 8 to 14-membered aromatic ring- condensed alicyclic hydrocarbon group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set 4b 9b V and substituent set V ), n is 0, 1 or 2, R is a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a sulfamoyl group, a phosphono group, a phosphonooxy group, a sulfo group, a sulfoxy group, a tetrazolyl group, a halogen atom, a cyano group, a nitro group, a C alkyl group, a C haloalkyl group, a C cycloalkyl group, a C alkenyl group, a C 1-6 3-11 2-6 2-6 haloalkenyl group, a C alkoxy group, a C haloalkoxy group, a C alkylthio group, a 1-6 1-6 1-6 C haloalkylthio group, a C alkylcarbonyl group, a C haloalkylcarbonyl group, a C 1-6 1-6 1-6 1- alkylsulfonyl group, a C haloalkylsulfonyl group, a C alkoxycarbonyl group, a 6 1-6 1-6 mono-C alkylamino group, a di-C alkylamino group, a mono-C 1-6 1-6 1-6 alkylaminocarbonyl group, a di-C alkylaminocarbonyl group or a C 1-6 1-6 b 3b alkylcarbonylamino group (when n is 2, R ’s may be identical or different), 4b 5b 6b 7b 8b 9b each of R , R , R , R , R and R is independently a hydrogen atom, a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a tetrazolyl group, a halogen atom, a cyano group, a C alkyl group, a C alkenyl group, a C alkoxy 1-6 2-6 1-6 group, a C alkylthio group, a C alkylcarbonyl group, a C alkylsulfonyl group, a 1-6 1-6 1-6 mono-C alkylamino group, a di-C alkylamino group (the C alkyl group, the C 1-6 1-6 1-6 2-6 alkenyl group, the C alkoxy group, the C alkylthio group, the C alkylcarbonyl 1-6 1-6 1-6 group, the C alkylsulfonyl group, the mono-C alkylamino group and the di-C 1-6 1-6 1-6 alkylamino group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a C alkoxycarbonyl group, a C cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a 3-11 C aryl group or a 5 to 10-membered aromatic heterocyclyl group (the C cycloalkyl 6-14 3-11 group, the 3 to 11-membered non-aromatic heterocyclyl group, the C aryl group and 6-14 the 5 to 10-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), 10b 11b each of R and R is independently a hydrogen atom, a C alkyl group, a C 1-6 2-6 alkenyl group, a C alkylcarbonyl group, a C alkylsulfonyl group, a C 1-6 1-6 1-6 alkoxycarbonyl group, a mono-C alkylaminocarbonyl group, a di-C 1-6 1-6 alkylaminocarbonyl group (the C alkyl group, the C alkenyl group, the C 1-6 2-6 1-6 alkylcarbonyl group, the C alkylsulfonyl group, the C alkoxycarbonyl group, the 1-6 1-6 mono-C alkylaminocarbonyl group and the di-C alkylaminocarbonyl group are 1-6 1-6 unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a C cycloalkyl group, a 3 to 11- 3-11 membered non-aromatic heterocyclyl group, a C aryl group or a 5 to 10-membered 6-14 aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11-membered non- 3-11 aromatic heterocyclyl group, the C aryl group and the 5 to 10-membered aromatic 6-14 40 heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), 12b 13b 14b each of R , R and R is independently a hydrogen atom, a C alkyl group or a C 1-6 1- haloalkyl group (the C alkyl group and the C haloalkyl group are unsubstituted or 6 1-6 1-6 substituted with one or more identical or different substituents independently selected 3b 8b 9b 45 from the substituent set V , the substituent set V and the substituent set V ), 15b 16b each of R and R is independently a hydrogen atom, a halogen atom, a cyano group, a carbamoyl group, a C alkyl group, a C haloalkyl group, a C cycloalkyl 1-6 1-6 3-11 group, a C alkoxy group, a C haloalkoxy group, a C alkylthio group, a C 1-6 1-6 1-6 1-6 alkylcarbonyl group, a C alkylsulfonyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a C aryl group or a 5 to 10-membered aromatic heterocyclyl 6-14 group, 17b 18b each of R and R is independently a hydrogen atom, a hydroxy group, a cyano group, a nitro group, a C alkyl group or a C alkoxy group, 1-6 1-6 the substituent set V consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C alkyl groups, C haloalkyl groups, C cycloalkyl groups, C alkenyl groups, C 1-6 1-6 3-11 2-6 2-6 haloalkenyl groups, C alkoxy groups, C haloalkoxy groups, C alkylthio groups, C 1-6 1-6 1-6 1- haloalkylthio groups, C alkylcarbonyl groups, C haloalkylcarbonyl groups, C 6 1-6 1-6 1-6 alkylsulfonyl groups, C haloalkylsulfonyl groups, C alkoxycarbonyl groups, 3 to 11- 1-6 1-6 membered non-aromatic heterocyclyl groups, mono-C alkylamino groups, di-C 1-6 1-6 alkylamino groups, mono-C alkylaminocarbonyl groups, di-C alkylaminocarbonyl 1-6 1-6 groups and C alkylcarbonylamino groups, 2b 1b the substituent set V consists of the groups in the substituent set V , and C aryl 6-14 groups and 5 to 10-membered aromatic heterocyclyl groups (the C aryl groups and 6-14 the 5 to 10-membered aromatic heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), the substituent set V consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C alkoxy groups, C haloalkoxy groups, C alkylthio groups, C haloalkylthio 1-6 1-6 1-6 1-6 groups, C alkylcarbonyl groups, C haloalkylcarbonyl groups, C alkylsulfonyl 1-6 1-6 1-6 groups, C haloalkylsulfonyl groups, C alkoxycarbonyl groups, mono-C alkylamino 1-6 1-6 1-6 groups, di-C alkylamino groups, mono-C alkylaminocarbonyl groups, di-C 1-6 1-6 1-6 alkylaminocarbonyl groups, C alkylcarbonylamino groups, C cycloalkyl groups, 3 to 1-6 3-11 11-membered non-aromatic heterocyclyl groups, C aryl group and 5 to 10-membered 6-14 aromatic heterocyclyl groups (the C cycloalkyl groups, the 3 to 11-membered non- 3-11 aromatic heterocyclyl groups, the C aryl groups and the 5 to 10-membered aromatic 6-14 heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), the substituent set V consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C alkyl groups, C alkenyl groups, C alkoxy groups, C alkylthio groups, C 1-6 2-6 1-6 1-6 1-6 alkylcarbonyl groups, C alkylsulfonyl groups, C alkoxycarbonyl groups, mono-C 1-6 1-6 1-6 40 alkylamino groups, di-C alkylamino groups, mono-C alkylaminocarbonyl groups, di- 1-6 1-6 C alkylaminocarbonyl groups, C alkylcarbonylamino groups (the C alkyl groups, 1-6 1-6 1-6 the C alkenyl groups, the C alkoxy groups, the C alkylthio groups, the C 2-6 1-6 1-6 1-6 alkylcarbonyl groups, the C alkylsulfonyl groups, the C alkoxycarbonyl groups, the 1-6 1-6 mono-C alkylamino groups, the di-C alkylamino groups, the mono-C 1-6 1-6 1-6 45 alkylaminocarbonyl groups, the di-C alkylaminocarbonyl groups and the C 1-6 1-6 alkylcarbonylamino groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), C 3-11 cycloalkyl groups, 3 to 11-membered non-aromatic heterocyclyl groups, C aryl 6-14 groups and 5 to 10-membered aromatic heterocyclyl groups (the C cycloalkyl groups, 3-11 the 3 to 11-membered non-aromatic heterocyclyl groups, the C aryl groups and the 5 6-14 to 10-membered aromatic heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), the substituent set V consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C alkoxy groups, C alkylthio groups, C alkylcarbonyl groups, C alkylsulfonyl 1-6 1-6 1-6 1-6 groups, C alkoxycarbonyl groups, mono-C alkylamino groups, di-C alkylamino 1-6 1-6 1-6 groups, mono-C alkylaminocarbonyl groups, di-C alkylaminocarbonyl groups, C 1-6 1-6 1-6 alkylcarbonylamino groups, C cycloalkyl groups, 3 to 11-membered non-aromatic 3-11 heterocyclyl groups, C aryl groups and 5 to 10-membered aromatic heterocyclyl 6-14 groups (the C alkoxy groups, the C alkylthio groups, the C alkylcarbonyl groups, 1-6 1-6 1-6 the C alkylsulfonyl groups, the C alkoxycarbonyl groups, the mono-C alkylamino 1-6 1-6 1-6 groups, the di-C alkylamino groups, the mono-C alkylaminocarbonyl groups, the di- 1-6 1-6 C alkylaminocarbonyl groups, the C alkylcarbonylamino groups, the C cycloalkyl 1-6 1-6 3-11 groups, the 3 to 11-membered non-aromatic heterocyclyl groups, the C aryl groups 6-14 and the 5 to 10-membered aromatic heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), the substituent set V consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C alkoxy groups, C alkylthio groups, C alkylcarbonyl groups, C alkylsulfonyl 1-6 1-6 1-6 1-6 groups, C alkoxycarbonyl groups, mono-C alkylamino groups, di-C alkylamino 1-6 1-6 1-6 groups, mono-C alkylaminocarbonyl groups, di-C alkylaminocarbonyl groups, C 1-6 1-6 1-6 alkylcarbonylamino groups (the C alkoxy groups, the C alkylthio groups, the C 1-6 1-6 1-6 alkylcarbonyl groups, the C alkylsulfonyl groups, the C alkoxycarbonyl groups, the 1-6 1-6 mono-C alkylamino groups, the di-C alkylamino groups, the mono-C 1-6 1-6 1-6 alkylaminocarbonyl groups, the di-C alkylaminocarbonyl groups and the C 1-6 1-6 alkylcarbonylamino groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), C 3-11 cycloalkyl groups, 3 to 11-membered non-aromatic heterocyclyl groups, C aryl 6-14 groups, 5 to 10-membered aromatic heterocyclyl groups, 8 to 14-membered partially saturated aromatic cyclic groups and 8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon groups (the C cycloalkyl groups, the 3 to 11-membered non- 3-11 aromatic heterocyclyl groups, the C aryl groups, the 5 to 10-membered aromatic 6-14 40 heterocyclyl groups, the 8 to 14-membered partially saturated aromatic cyclic groups and the 8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon groups are unsubstituted or substituted with one or more identical or different substituents 4b 9b independently selected from the substituent set V and the substituent set V ), and the substituent set V consists of 8 to 14-membered partially saturated aromatic cyclic 45 groups and 8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon groups (the 8 to 14-membered partially saturated aromatic cyclic groups and the 8 to 14- membered aromatic ring-condensed alicyclic hydrocarbon groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), the substituent set V consists of, mono-C alkylaminosulfonyl groups, di-C 1-6 1-6 alkylaminosulfonyl groups, C alkylsulfonylamino groups (the mono-C 1-6 1-6 alkylaminosulfonyl groups, di-C alkylaminosulfonyl groups and C alkylsulfonylamino 1-6 1-6 groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), C cycloalkoxy groups, C cycloalkylamino groups, C cycloalkylthio groups, C cycloalkylcarbonyl 3-6 3-6 3-6 groups and C cycloalkylsulfonyl groups (the C cycloalkoxy groups, the C 3-6 3-6 3-6 cycloalkylamino groups, the C cycloalkylthio groups, the C cycloalkylcarbonyl 3-6 3-6 groups and the C cycloalkylsulfonyl groups unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V )], a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (42) The compound according to (41), which is represented by the formula (I ): (R ) b ( I ) [wherein the ring A is represented by the formula (II ): (II ) 1b 4b 5b 17b 1b (wherein T is CR R , C(=O), C(=S), C(=NR ), a sulfur atom, S(=O) or S(=O) , U 6b 1b 8b b is a nitrogen atom or CR , and W is a nitrogen atom or CR ), the formula (III ): (III ) 2b 4b 2b 6b 2b 8b 9b (wherein T is CR , U is a nitrogen atom or CR , and W is CR R , C(=O), C(=S), 17b 10b C(=NR ), NR , an oxygen atom, a sulfur atom, S(=O) or S(=O) (provided that when 2b 6b 2b b U is CR , W is not C(=O))), or the formula (IV ): 3b (IV ) 3b 4b 5b 17b 3b (wherein T is CR R , C(=O), C(=S), C(=NR ), a sulfur atom, S(=O) or S(=O) , U 6b 7b 17b 10b is CR R , C(=O), C(=S), C(=NR ), NR , an oxygen atom, a sulfur atom, S(=O) or 3b 8b 9b 17b 11b S(=O) , and W is CR R , C(=O), C(=S), C(=NR ), NR , an oxygen atom, a sulfur 3b 4b 5b 3b 6b 7b 3b atom, S(=O) or S(=O) (provided that when T is CR R and U is CR R , W is 8b 9b not CR R )), b 15b X is a nitrogen atom or CR , b 16b Y is CR , R is a hydrogen atom, a halogen atom, a C alkyl group or a C haloalkyl group, 1-6 1-6 the ring B is a C cycloalkane, a C cycloalkene, a 3 to 11-membered non-aromatic 3-11 3-11 heterocycle, a C aromatic carbocycle or a 5 to 10-membered aromatic heterocycle, 6-14 L is a single bond, a C alkylene group, a C alkenylene group or a C alkynylene 1-6 2-6 2-6 group (the C alkylene group, the C alkenylene group and the C alkynylene group 1-6 2-6 2-6 are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, amino groups, cyano groups and nitro groups), L is a single bond, a C alkylene group, a C alkenylene group or a C alkynylene 1-6 2-6 2-6 group (the C alkylene group, the C alkenylene group and the C alkynylene group 1-6 2-6 2-6 are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, amino groups, cyano groups and nitro groups), 3b b b L is a single bond or represented by any of the following formulae (V -1) to (V -20): 12b 1b O b b R E ( V -1 ) ( V -2 ) b b b b (V -3 ) (V -4 ) ( V -5 ) ( V -6 ) 1b 13b b b b b b ( V -7 ) (V -8 ) (V -9 ) (V -10 ) ( V -11 ) ( V ) 1b 1b N N N 12b 12b 13b R R R b b b b b (V -12 ) (V -13 ) ( V -14 ) ( V -15 ) (V -16 ) 1b 14b 1b 1b O N N O N N 12b 12b 13b 12b 13b R R R R R b b b b (V -17 ) ( V -18 ) (V -19 ) (V -20 ) 1b 18b (wherein E is an oxygen atom, a sulfur atom or NR ), 3b 2b when L is a single bond, R is a hydrogen atom, a halogen atom, a C cycloalkyl 3-11 group, a 3 to 11-membered non-aromatic heterocyclyl group, a C aryl group or a 5 to 6-14 -membered aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11- 3-11 membered non-aromatic heterocyclyl group, the C aryl group and the 5 to 10- 6-14 membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), 3b 2b when L is not a single bond, R is a hydrogen atom, a C alkyl group, a C alkenyl 1-6 2-6 group (the C alkyl group and the C alkenyl group are unsubstituted or substituted 1-6 2-6 with one or more identical or different substituents independently selected from the substituent set V ), a C cycloalkyl group, a 3 to 11-membered non-aromatic 3-11 heterocyclyl group, a C aryl group or a 5 to 10-membered aromatic heterocyclyl 6-14 group (the C cycloalkyl group, the 3 to 11-membered non-aromatic heterocyclyl 3-11 group, the C aryl group and the 5 to 10-membered aromatic heterocyclyl group are 6-14 unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), n is 0, 1 or 2, R is a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a sulfamoyl group, a phosphono group, a phosphonooxy group, a sulfo group, a sulfoxy group, a tetrazolyl group, a halogen atom, a cyano group, a nitro group, a C alkyl group, a C haloalkyl group, a C cycloalkyl group, a C alkenyl group, a C 1-6 3-11 2-6 2-6 haloalkenyl group, a C alkoxy group, a C haloalkoxy group, a C alkylthio group, a 1-6 1-6 1-6 C haloalkylthio group, a C alkylcarbonyl group, a C haloalkylcarbonyl group, a C 1-6 1-6 1-6 1- alkylsulfonyl group, a C haloalkylsulfonyl group, a C alkoxycarbonyl group, a 6 1-6 1-6 mono-C alkylamino group, a di-C alkylamino group, a mono-C 1-6 1-6 1-6 alkylaminocarbonyl group, a di-C alkylaminocarbonyl group or a C 1-6 1-6 b 3b alkylcarbonylamino group (when n is 2, R ’s may be identical or different), 4b 5b 6b 7b 8b 9b each of R , R , R , R , R and R is independently a hydrogen atom, a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a tetrazolyl group, a halogen atom, a cyano group, a C alkyl group, a C alkenyl group, a C alkoxy 1-6 2-6 1-6 group, a C alkylthio group, a C alkylcarbonyl group, a C alkylsulfonyl group, a 1-6 1-6 1-6 mono-C alkylamino group, a di-C alkylamino group (the C alkyl group, the C 1-6 1-6 1-6 2-6 alkenyl group, the C alkoxy group, the C alkylthio group, the C alkylcarbonyl 1-6 1-6 1-6 group, the C alkylsulfonyl group, the mono-C alkylamino group and the di-C 1-6 1-6 1-6 alkylamino group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a C alkoxycarbonyl group, a C cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a 3-11 C aryl group or a 5 to 10-membered aromatic heterocyclyl group (the C cycloalkyl 6-14 3-11 group, the 3 to 11-membered non-aromatic heterocyclyl group, the C aryl group and 6-14 40 the 5 to 10-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), 10b 11b each of R and R is independently a hydrogen atom, a C alkyl group, a C 1-6 2-6 alkenyl group, a C alkylcarbonyl group, a C alkylsulfonyl group, a C 1-6 1-6 1-6 45 alkoxycarbonyl group, a mono-C alkylaminocarbonyl group, a di-C 1-6 1-6 alkylaminocarbonyl group (the C alkyl group, the C alkenyl group, the C 1-6 2-6 1-6 alkylcarbonyl group, the C alkylsulfonyl group, the C alkoxycarbonyl group, the 1-6 1-6 mono-C alkylaminocarbonyl group and the di-C alkylaminocarbonyl group are 1-6 1-6 unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a C cycloalkyl group, a 3 to 11- 3-11 membered non-aromatic heterocyclyl group, a C aryl group or a 5 to 10-membered 6-14 aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11-membered non- 3-11 aromatic heterocyclyl group, the C aryl group and the 5 to 10-membered aromatic 6-14 heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), 12b 13b 14b each of R , R and R is independently a hydrogen atom, a C alkyl group or a C 1-6 1- haloalkyl group (the C alkyl group and the C haloalkyl group are unsubstituted or 6 1-6 1-6 substituted with one or more identical or different substituents independently selected from the substituent set V ), 15b 16b each of R and R is independently a hydrogen atom, a halogen atom, a cyano group, a carbamoyl group, a C alkyl group, a C haloalkyl group, a C cycloalkyl 1-6 1-6 3-11 group, a C alkoxy group, a C haloalkoxy group, a C alkylthio group, a C 1-6 1-6 1-6 1-6 alkylcarbonyl group, a C alkylsulfonyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a C aryl group or a 5 to 10-membered aromatic heterocyclyl 6-14 group, 17b 18b each of R and R is independently a hydrogen atom, a hydroxy group, a cyano group, a nitro group, a C alkyl group or a C alkoxy group, 1-6 1-6 the substituent set V consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C alkyl groups, C haloalkyl groups, C cycloalkyl groups, C alkenyl groups, C 1-6 1-6 3-11 2-6 2-6 haloalkenyl groups, C alkoxy groups, C haloalkoxy groups, C alkylthio groups, C 1-6 1-6 1-6 1- haloalkylthio groups, C alkylcarbonyl groups, C haloalkylcarbonyl groups, C 6 1-6 1-6 1-6 alkylsulfonyl groups, C haloalkylsulfonyl groups, C alkoxycarbonyl groups, 3 to 11- 1-6 1-6 membered non-aromatic heterocyclyl groups, mono-C alkylamino groups, di-C 1-6 1-6 alkylamino groups, mono-C alkylaminocarbonyl groups, di-C alkylaminocarbonyl 1-6 1-6 groups and C alkylcarbonylamino groups, 2b 1b the substituent set V consists of the groups in the substituent set V and C aryl 6-14 groups and 5 to 10-membered aromatic heterocyclyl groups (the C aryl groups and 5 6-14 to 10-membered aromatic heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), the substituent set V consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C alkoxy groups, C haloalkoxy groups, C alkylthio groups, C haloalkylthio 1-6 1-6 1-6 1-6 40 groups, C alkylcarbonyl groups, C haloalkylcarbonyl groups, C alkylsulfonyl 1-6 1-6 1-6 groups, C haloalkylsulfonyl groups, C alkoxycarbonyl groups, mono-C alkylamino 1-6 1-6 1-6 groups, di-C alkylamino groups, mono-C alkylaminocarbonyl groups, di-C 1-6 1-6 1-6 alkylaminocarbonyl groups, C alkylcarbonylamino groups, C cycloalkyl groups, 3 to 1-6 3-11 11-membered non-aromatic heterocyclyl groups, C aryl groups and 5 to 10- 6-14 45 membered aromatic heterocyclyl groups (the C cycloalkyl groups, the 3 to 11- 3-11 membered non-aromatic heterocyclyl groups, the C aryl groups and the 5 to 10- 6-14 membered aromatic heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), the substituent set V consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C alkyl groups, C alkenyl groups, C alkoxy groups, C alkylthio groups, C 1-6 2-6 1-6 1-6 1-6 alkylcarbonyl groups, C alkylsulfonyl groups, C alkoxycarbonyl groups, mono-C 1-6 1-6 1-6 alkylamino groups, di-C alkylamino groups, mono-C alkylaminocarbonyl groups, di- 1-6 1-6 C alkylaminocarbonyl groups, C alkylcarbonylamino groups (the C alkyl groups, 1-6 1-6 1-6 the C alkenyl groups, the C alkoxy groups, the C alkylthio groups, the C 2-6 1-6 1-6 1-6 alkylcarbonyl groups, the C alkylsulfonyl groups, the C alkoxycarbonyl groups, the 1-6 1-6 mono-C alkylamino groups, the di-C alkylamino groups, the mono-C 1-6 1-6 1-6 alkylaminocarbonyl groups, the di-C alkylaminocarbonyl groups and the C 1-6 1-6 alkylcarbonylamino groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), C 3-11 cycloalkyl groups, 3 to 11-membered non-aromatic heterocyclyl groups, C aryl 6-14 groups and 5 to 10-membered aromatic heterocyclyl groups (the C cycloalkyl groups, 3-11 the 3 to 11-membered non-aromatic heterocyclyl groups, the C aryl groups and the 5 6-14 to 10-membered aromatic heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), and the substituent set V consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C alkoxy groups, C alkylthio groups, C alkylcarbonyl groups, C alkylsulfonyl 1-6 1-6 1-6 1-6 groups, C alkoxycarbonyl groups, mono-C alkylamino groups, di-C alkylamino 1-6 1-6 1-6 groups, mono-C alkylaminocarbonyl groups, di-C alkylaminocarbonyl groups, C 1-6 1-6 1-6 alkylcarbonylamino groups, C cycloalkyl groups, 3 to 11-membered non-aromatic 3-11 heterocyclyl groups, C aryl groups and 5 to 10-membered aromatic heterocyclyl 6-14 groups (the C alkoxy groups, the C alkylthio groups, the C alkylcarbonyl groups, 1-6 1-6 1-6 the C alkylsulfonyl groups, the C alkoxycarbonyl groups, the mono-C alkylamino 1-6 1-6 1-6 groups, the di-C alkylamino groups, the mono-C alkylaminocarbonyl groups, the di- 1-6 1-6 C alkylaminocarbonyl groups, the C alkylcarbonylamino groups, the C cycloalkyl 1-6 1-6 3-11 groups, the 3 to 11-membered non-aromatic heterocyclyl groups, the C aryl groups 6-14 and the 5 to 10-membered aromatic heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V )], a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (43) The compound according to (42), wherein R is a hydrogen atom, a tautomer or a 40 pharmaceutically acceptable salt of the compound or a solvate thereof. b 15b (44) The compound according to (42) or (43), wherein X is a nitrogen atom or CR (wherein R is a hydrogen atom, a halogen atom, a cyano group, a C alkyl group, a C haloalkyl group or a C cycloalkyl group), and 1-3 3-6 b 16b 16b Y is CR (wherein R is a hydrogen atom), a tautomer or a pharmaceutically 45 acceptable salt of the compound or a solvate thereof. b 15b (45) The compound according to (44), wherein X is a nitrogen atom or CR (wherein R is a hydrogen atom or a halogen atom), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (46) The compound according to any one of (42) to (45), wherein the ring A is represented by the formula (II ): (II ) 1b 4b 5b 1b 6b (wherein T is CR R , C(=O), C(=S) or S(=O) , U is a nitrogen atom or CR , and 1b 8b b W is CR ), the formula (III ): (III ) 2b 4b 2b 2b (wherein T is CR , U is a nitrogen atom, and W is C(=O) or C(=S)) or the formula (IV ): 3b (IV ) 3b 4b 5b 3b 10b 3b 8b 9b (wherein T is CR R , U is NR or an oxygen atom, and W is CR R , C(=O) or C(=S)), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (47) The compound according to any one of (42) to (45), wherein the ring A is represented by any of the following formulae (XVIII -1) to (XVIII -8): 8b 8b N N N N N N b b b b (XVIII -1 ) (XVIII -2 ) (XVIII -3 ) (XVIII -4 ) ( XVIII ) 2b 9b E 8b 5b E b b b b (XVIII -5 ) (XVIII -6 ) (XVIII -7 ) ( XVIII -8 ) 2b 3b (wherein each of E and E is independently an oxygen atom or a sulfur atom, each of 4b 5b 6b 8b 9b R , R , R , R and R is independently a hydrogen atom, a halogen atom or a C alkyl group, and R is a hydrogen atom or a C alkyl group), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (48) The compound according to any one of (42) to (47), wherein L is a single bond, L is a single bond, a C alkylene group or a C alkenylene group (the C alkylene 1-6 2-6 1-6 group and the C alkenylene group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of a halogen atoms, hydroxy groups, amino groups, cyano groups and nitro groups), the ring B is a C cycloalkane, a C cycloalkene, a 3 to 11-membered non-aromatic 3-11 3-11 heterocycle, a C aromatic carbocycle or a 5 to 10-membered aromatic heterocycle, 6-14 n is, 0 or 1, R is a hydroxy group, an amino group, a halogen atom, a cyano group, a C alkyl group, a C haloalkyl group, a C cycloalkyl group, a C alkoxy group, a C 1-3 3-6 1-3 1-3 haloalkoxy group or a C alkylsulfonyl group, L is a single bond, and R is a hydrogen atom, a halogen atom, a C cycloalkyl group, a 3 to 11-membered 3-11 non-aromatic heterocyclyl group, a phenyl group, a naphthyl group or a 5 to 10- membered aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11- 3-11 membered non-aromatic heterocyclyl group, the phenyl group, the naphthyl group and the 5 to 10-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (49) The compound according to any one of (42) to (47), wherein L is a single bond or a C alkylene group, L is a single bond or a C alkylene group (the C alkylene group is unsubstituted or 1-3 1-3 substituted with a cyano group or a C haloalkyl group), the ring B is a C cycloalkane, a C cycloalkene, a 3 to 11-membered non-aromatic 3-11 3-11 heterocycle, benzene or a 5 to 6-membered aromatic heterocycle, n is, 0 or 1, R is a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a tetrazolyl group, a halogen atom, a cyano group, a nitro group, a C alkyl group, a C 1-3 1-3 haloalkyl group, a C cycloalkyl group, a C alkoxy group, a C haloalkoxy group or 3-6 1-3 1-3 a C alkylsulfonyl group, L is a single bond, and R is a hydrogen atom, a halogen atom, a C cycloalkyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different 40 substituents independently selected from the substituent set V ), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (50) The compound according to (48), wherein the ring B is a C cycloalkane or a 4 3-11 to 7-membered non-aromatic heterocycle, n is 0 or 1, and 45 R is a hydroxy group, a C alkyl group or a C alkoxy group, a tautomer or a 1-3 1-3 pharmaceutically acceptable salt of the compound or a solvate thereof. (51) The compound according to (48) or (50), wherein L is a single bond, a C alkylene group, a C alkenylene group or a C haloalkylene group (the C alkylene 2-6 1-6 1-6 group, the C alkenylene group and the C haloalkylene group are unsubstituted or 2-6 1-6 substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups and cyano groups), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (52) The compound according to any one of (48), (50) and (51), wherein R is a hydrogen atom, a C cycloalkyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 10-membered aromatic heterocyclyl group (the 4 to 7- membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 10- membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of hydroxy groups, amino groups, carbamoyl groups, sulfamoyl groups, halogen atoms, cyano groups, nitro groups, C alkyl groups, C alkoxy groups, C alkylthio groups, 1-6 1-6 1-6 C alkylsulfonyl groups, mono-C alkylamino groups, di-C alkylamino groups, C 1-6 1-6 1-6 1-6 alkoxycarbonyl groups, mono-C alkylaminocarbonyl groups, di-C 1-6 1-6 alkylaminocarbonyl groups, C alkylcarbonylamino groups (the C alkyl groups, the 1-6 1-6 C alkoxy groups, the C alkylthio groups, the C alkylsulfonyl groups, the mono-C 1-6 1-6 1-6 1-6 alkylamino groups, the di-C alkylamino groups, the C alkoxycarbonyl groups, the 1-6 1-6 mono-C alkylaminocarbonyl groups, the di-C alkylaminocarbonyl groups and the C 1-6 1-6 1- alkylcarbonylamino groups are unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms or with a hydroxy group or a cyano group), C cycloalkyl groups, 4 to 7-membered non-aromatic heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (53) The compound according to (52), wherein R is a hydrogen atom, a 4 to 7- membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 10-membered aromatic heterocyclyl group (the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 10-membered aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, halogen atoms, cyano groups, nitro groups, C alkyl groups (the C alkyl groups are unsubstituted or substituted with a cyano 1-3 1-3 group), C haloalkyl groups and C alkoxycarbonyl groups), a tautomer or a 1-3 1-6 pharmaceutically acceptable salt of the compound or a solvate thereof. (54) The compound according to any one of (48) and (50) to (53), wherein L is a C alkylene group, a C alkenylene group (the C alkylene group and the C alkenylene 2-3 1-6 2-3 group are unsubstituted or substituted with a cyano group) or C haloalkylene group, and R is, a hydrogen atom, a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. 40 (55) The compound according to any one of (42) to (47), wherein L is a single bond, L is a single bond, a C alkylene group or a C alkenylene group (the C alkylene 1-6 2-6 1-6 group and the C alkenylene group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, amino groups, cyano groups and nitro groups), 45 the ring B is a C cycloalkane, a C cycloalkene, a 3 to 11-membered non-aromatic 3-11 3-11 heterocyclyl group, a C aryl group or a 5 to 10-membered aromatic heterocycle, 6-14 n is 0 or 1, R is a hydroxy group, an amino group, a halogen atom, a cyano group, a C alkyl group, a C haloalkyl group, a C cycloalkyl group, a C alkoxy group or a C 1-3 3-6 1-3 1-3 haloalkoxy group, 3b b b L is represented by any of the following formulae (VI -1) to (VI -11): 12b 1b 12b E E 1b b b b b b b (VI -6 ) (VI -1 ) (VI -2 ) (VI -3 ) (VI -4 ) (VI -5 ) O O (VI ) 12b 13b 12b 13b R R 12b b b b (VI -10 ) (VI -11 ) (VI -7 ) (VI -8 ) (VI -9 ) 1b 12b 13b (wherein E is an oxygen atom or a sulfur atom, each of R and R is independently a hydrogen atom, a C alkyl group or a C haloalkyl group (the C alkyl group and 1-6 1-6 1-6 the C haloalkyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, cyano groups, hydroxy group, C alkoxy groups, C alkylthio groups, C 1-6 1-6 1-6 alkylsulfonyl groups, C cycloalkyl groups, 4 to 7-membered non-aromatic heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups (the phenyl groups and the 5 to 6-membered aromatic heterocyclyl groups are unsubstituted or substituted with a substituent selected from the group consisting of a halogen atom, a cyano group, a C alkyl group and a C haloalkyl group))), and 1-3 1-3 R is a hydrogen atom, a C alkyl group (the C alkyl group is unsubstituted or 1-6 1-6 substituted with one or more identical or different substituents independently selected from the substituent set V ), a C cycloalkyl group, a 3 to 11-membered non-aromatic 3-11 heterocyclyl group, a phenyl group, a naphthyl group or a 5 to 10-membered aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11-membered non-aromatic 3-11 heterocyclyl group, the phenyl group, the naphthyl group and the 5 to 10-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (56) The compound according to any one of (42) to (47), wherein L is a single bond or a C alkylene group, L is a single bond or a C alkylene group (the C alkylene group is unsubstituted or 1-3 1-3 substituted with a cyano group or a C haloalkyl group), the ring B is a C cycloalkane, a C cycloalkene, a 3 to 11-membered non-aromatic 3-11 3-11 heterocycle, benzene or a 5 to 6-membered aromatic heterocycle, n is 0 or 1, R is a hydroxy group, an amino group, a carbamoyl group, a halogen atom, a cyano group, a C alkyl group, a C haloalkyl group, a C cycloalkyl group, a C alkoxy 1-3 1-3 3-6 1-3 group, a C haloalkoxy group or a C alkylsulfonyl group, 1-3 1-3 3b b b L is represented by any of the following formulae (VI -1) to (VI -11): 12b E 1b O b b b b b (VI -6 ) (VI -1 ) (VI -2 ) (VI -3 ) (VI -4 ) (VI -5 ) O O (VI ) 12b 13b R 12b 13b b b b (VI -10 ) (VI -11 ) (VI -7 ) (VI -8 ) (VI -9 ) 1b 12b 13b (wherein E is an oxygen atom, each of R and R is independently a hydrogen atom, a C alkyl group or a C haloalkyl group), and 1-6 1-6 R is a hydrogen atom, a C alkyl group (the C alkyl group is unsubstituted or 1-6 1-6 substituted with one or more identical or different substituents independently selected from the substituent set V ), a C cycloalkyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (57) The compound according to (55), wherein the ring B is a C cycloalkane or a 4 3-11 to 7-membered non-aromatic heterocycle, 3b b b L is represented by any of the following formulae (XIX -1) to (XIX -7): 1b 12b (wherein E is an oxygen atom, and R is a hydrogen atom, a C alkyl group (the C 1-6 1- alkyl group is unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of cyano groups, hydroxy groups, C alkoxy groups, C cycloalkyl groups and phenyl groups) or a C haloalkyl 1-3 3-6 1-6 group), and R is a hydrogen atom, a C alkyl group, a C haloalkyl group (the C alkyl group 1-6 1-6 1-6 and the C haloalkyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, cyano groups, C alkoxy groups, C alkylthio groups, C alkylsulfonyl groups, 1-3 1-3 1-3 C cycloalkyl groups, 4 to 7-membered non-aromatic heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups (the C cycloalkyl groups, the 4 to 7-membered non-aromatic heterocyclyl groups, the phenyl groups and the 5 to 6-membered aromatic heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, cyano groups, C alkoxy groups, C haloalkoxy 1-6 1-6 groups and C alkoxycarbonyl groups)), a C cycloalkyl group, a 4 to 7-membered 1-6 3-6 non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, cyano groups, C alkyl groups, C haloalkyl groups, C alkoxy 1-6 1-6 1-6 groups, C haloalkoxy groups and C alkoxycarbonyl groups), a tautomer or a 1-6 1-6 pharmaceutically acceptable salt of the compound or a solvate thereof. (58) The compound according to (55) or (57), wherein L is represented by any of the following formulae (XX -1) to (XX -4): 1b 12b (wherein E is an oxygen atom, and R is a hydrogen atom, a C alkyl group (the C 1-3 1- alkyl group is unsubstituted or substituted with a substituent selected from the group consisting of a cyano group, a hydroxy group, a C alkoxy group, a C cycloalkyl 1-3 3-6 group and a phenyl group) or C haloalkyl group)), and R is a hydrogen atom, a C alkyl group, a C haloalkyl group (the C alkyl group 1-3 1-3 1-3 and the C haloalkyl group are unsubstituted or substituted with one or two identical or different substituent selected from the group consisting of hydroxy groups, cyano groups, C alkoxy groups, C cycloalkyl groups, 4 to 7-membered non-aromatic heterocyclyl 1-3 3-6 groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups (the C cycloalkyl groups, the 4 to 7-membered non-aromatic heterocyclyl groups, the phenyl groups and the 5 to 6-membered aromatic heterocyclyl groups are unsubstituted or substituted with a hydroxy group or a halogen atom)), a C cycloalkyl group, a 4 to 7- membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non- aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, halogen atoms, cyano groups, C alkyl groups, C haloalkyl groups and C 1-6 1-3 1-6 alkoxycarbonyl groups), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (59) The compound according to any one of (48) to (53) or (55) to (58), wherein L is a single bond or a C alkylene group, a tautomer or a pharmaceutically acceptable salt 40 of the compound or a solvate thereof. (60) The compound according to any one of (44) to (59), wherein X is a nitrogen atom 15b 15b or CR (wherein R is a hydrogen atom), and b 16b 16b Y is CR (wherein R is a hydrogen atom), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (61) The compound according to any one of (46) to (60), wherein the ring A is represented by any of the following formulae (VII -1) to (VII -7): 8b 8b 8b 8b R R R N N N b b b b ( VII -1 ) ( VII -2 ) ( VII -3 ) ( VII -4 ) E 8b b R (VII ) b b b ( VII -5 ) ( VII -6 ) ( VII -7 ) 2b 4b 5b 6b 8b 9b 10b (wherein E is an oxygen atom, and each of R , R , R , R , R and R is independently a hydrogen atom or a C alkyl group), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (62) The compound according to any one of (46) to (60), wherein the ring A is represented by any of the following formulae (XXXIII -1) to (XXXIII -3): 8b E 8b 6b R ( XXXIII ) b b b (XXXIII -1 ) (XXXIII -2) (XXXIII -3 ) 2b 4b 5b 8b 9b 10b (wherein E is an oxygen atom, and each of R , R , R , R and R are hydrogen atoms, and R is a hydrogen atom, a halogen atom or a C alkyl group), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (63) The compound according to any one of (49), (60) and (61), wherein L is a single bond, L is a C alkylene group, the ring B is a C cycloalkane or a 4 to 7-membered non-aromatic heterocycle, n is 0 or 1, R is a C alkyl group, L is a single bond, and R is a hydrogen atom or a phenyl group (the phenyl group is unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (64) The compound according to any one of (49), (60) and (61), wherein L is a single bond, L is a single bond, the ring B is a C cycloalkane or a 4 to 7-membered non-aromatic heterocycle, n is 0, L is a single bond, and R is a hydrogen atom, a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (65) The compound according to any one of (56), (60) and (61), wherein L is a single bond, L is a single bond, the ring B is a C cycloalkane or a 4 to 7-membered non-aromatic heterocycle, n is 0 or 1, R is a C alkyl group, 3b b b L is represented by any of the following formula (VIII -1) or (VIII -2): ( VIII ) (VIII -1) (VIII -2) , and R is a C alkyl group (the C alkyl group is unsubstituted or substituted with a cyano 1-6 1-6 group or a C cycloalkyl group) or a C haloalkyl group, a tautomer or a 3-6 1-3 pharmaceutically acceptable salt of the compound or a solvate thereof. (66) The compound according to any one of (42) to (65), wherein the ring B is cyclohexane or piperidine, a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (67) The compound according to any one of (42) to (62), wherein the ring B is a 4 to 7-membered non-aromatic heterocycle, a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. b 15b (68) The compound according to (41), wherein X is a nitrogen atom or CR (wherein R is a hydrogen atom or a halogen atom), b 16b 16b Y is CR (wherein R is a hydrogen atom), R is a hydrogen atom, b b b the ring A is represented by any of the following formulae (XVIII -1) to (XVIII -8): 8b 8b 8b R R R N N N N N b b b b (XVIII -1 ) (XVIII -2 ) (XVIII -3 ) (XVIII -4 ) ( XVIII ) 9b 2b E 8b 5b E R 5b b b b b (XVIII -5 ) (XVIII -6 ) (XVIII -7 ) ( XVIII -8 ) 2b 3b (wherein each of E and E is independently an oxygen atom or a sulfur atom, each of 4b 5b 6b 8b 9b R , R , R , R and R is independently a hydrogen atom, a halogen atom or a C alkyl group, and R is a hydrogen atom, a C alkyl group (the C alkyl group is 1-6 1-6 unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a C cycloalkyl group, a 3 to 11- 3-11 membered non-aromatic heterocyclyl group, a C aryl group or a 5 to 10-membered 6-14 aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11-membered non- 3-11 aromatic heterocyclyl group, the C aryl group and the 5 to 10-membered aromatic 6-14 heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V )), the ring B is a C cycloalkane, a 3 to 11-membered non-aromatic heterocycle, a C 3-11 6-14 aromatic carbocycle or a 5 to 10-membered aromatic heterocycle, L is single bond or a C alkylene group, L is a single bond, a C alkylene group or a C alkenylene group (the C alkylene 1-6 2-6 1-6 group and the C alkenylene group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, amino groups, cyano groups and nitro groups), n is 0 or 1, R is a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a tetrazolyl group, a halogen atom, a cyano group, a nitro group, a C alkyl group, a C 1-3 1-3 haloalkyl group, a C cycloalkyl group, a C alkoxy group, a C haloalkoxy group or 3-6 1-3 1-3 a C alkylsulfonyl group, 3b b b L is a single bond or represented by any of the following formulae (XXII -1) to (XXII - 15): 1b 12b 13b (wherein E is an oxygen atom or a sulfur atom, and each of R and R is independently a hydrogen atom, a C alkyl group or a C haloalkyl group (the C 1-6 1-6 1-6 alkyl group and the C haloalkyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, cyano groups, hydroxy groups, C alkoxy groups, C alkylthio 1-6 1-6 groups, C alkylsulfonyl groups, C cycloalkyl groups, 4 to 7-membered non-aromatic 1-6 3-6 heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups (the phenyl groups and 5 to 6-membered aromatic heterocyclyl groups are unsubstituted or substituted with a substituent selected from the group consisting of a halogen atom, a cyano group, a C alkyl group and a C haloalkyl group))), 1-3 1-3 3b 2b when L is a single bond, R is a hydrogen atom, a halogen atom, a C cycloalkyl 3-11 group, a 3 to 11-membered non-aromatic heterocyclyl group, a phenyl group, a naphthyl group, a 5 to 10-membered aromatic heterocyclyl group, a 8 to 11-membered partially saturated aromatic cyclic group or a 8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon group (the C cycloalkyl group, the 3 to 11-membered non- 3-11 aromatic heterocyclyl group, the phenyl group, the naphthyl group, the 5 to 10- membered aromatic heterocyclyl group, the 8 to 11-membered partially saturated aromatic cyclic group and the 8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V and the substituent set V ), 3b 2b when L is not a single bond, R is a hydrogen atom, a C alkyl group, a C alkenyl 1-6 2-6 group (the C alkyl group and the C alkenyl group are unsubstituted or substituted 1-6 2-6 with one or more identical or different substituents independently selected from the 6b 9b substituent set V and the substituent set V ), a C cycloalkyl group, a 3 to 11- 3-11 membered non-aromatic heterocyclyl group, a C aryl group, a 5 to 10-membered 6-14 aromatic heterocyclyl group, a 8 to 11-membered partially saturated aromatic cyclic group or a 8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon group (the C cycloalkyl group, the 3 to 11-membered non-aromatic heterocyclyl group, the C 3-11 6-14 aryl group, the 5 to 10-membered aromatic heterocyclyl group, the 8 to 11-membered partially saturated aromatic cyclic group or the 8 to 11-membered aromatic ring- condensed alicyclic hydrocarbon group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set 4b 9b V and the substituent set V ), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (69) The compound according to (41) or (68), wherein the ring A is represented by any of the following formulae (XXI -1) to (XXI -4): 9b 2b 8b E 8b 6b R ( XXI ) 2b 5b E b b b b (XXI -1 ) (XXI -2) (XXI -3 ) ( XXI -4 ) 2b 3b 4b 5b (wherein each of E and E is independently an oxygen atom or a sulfur atom, R , R , 8b 9b 6b R and R are hydrogen atoms, R is a hydrogen atom, a halogen atom or a C alkyl group, and R is a hydrogen atom, a C alkyl group (the C alkyl group is 1-6 1-6 unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of cyano groups, hydroxy groups, C alkoxy groups, C alkylthio groups, mono-C alkylamino groups, di-C alkylamino 1-3 1-3 1-3 groups, mono-C alkylaminocarbonyl groups, di-C alkylaminocarbonyl groups, C 1-3 1-3 3-6 cycloalkyl groups, 4 to 7-membered non-aromatic heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups (the phenyl groups and the 5 to 6- membered aromatic heterocyclyl groups are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms, C alkyl groups and C haloalkyl groups)), a C haloalkyl group, a 1-3 1-3 1-6 C cycloalkyl group or a 4 to 7-membered non-aromatic heterocyclyl group), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (70) The compound according to any one of (41), (68) and (69), wherein the ring A is represented by the following formulae (XXIX -1) or (XXIX -2): ( XXIX ) ( XXIX -1) (XXIX -2) 2b 3b 6b (wherein E and E are oxygen atoms, R is a hydrogen atom, a halogen atom or a 8b 10b C alkyl group, R is a hydrogen atom, and R is a hydrogen atom, a C alkyl group 1-3 1-6 (the C alkyl group is unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of cyano groups, hydroxy groups, C alkoxy groups, C alkylthio groups, di-C alkylamino groups, C 1-3 1-3 1-3 3-6 cycloalkyl groups and 4 to 7-membered non-aromatic heterocyclyl groups), a C haloalkyl group, a C cycloalkyl group or a 4 to 7-membered non-aromatic heterocyclyl group, a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (71) The compound according to any one of (41) and (68) to (70), wherein L is a single bond, L is a single bond, a C alkylene group, a C alkenylene group or a C 1-6 2-6 1-6 haloalkylene group (the C alkylene group, the C alkenylene group and the C 1-6 2-6 1-6 haloalkylene group are unsubstituted or substituted with a hydroxy group or a cyano group), the ring B is a C cycloalkane or a 4 to 7-membered non-aromatic heterocycle, 3-11 n is 0 or 1, and R is a hydroxy group, a C alkyl group or a C alkoxy group, a tautomer or a 1-3 1-3 pharmaceutically acceptable salt of the compound or a solvate thereof. (72) The compound according to any one of (41) and (68) to (71), wherein L is a single bond, and R is a hydrogen atom, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group, a 5 to 10-membered aromatic heterocyclyl group or a 8 to 11-membered partially saturated aromatic cyclic group (the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group, the 5 to 10-membered aromatic heterocyclyl group and the 8 to 11- membered partially saturated aromatic cyclic group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of hydroxy groups, amino groups, carbamoyl groups, sulfamoyl groups, halogen atoms, cyano groups, nitro groups, C alkyl groups (the C alkyl groups are 1-6 1-6 unsubstituted or substituted with a cyano group), C haloalkyl groups, C cycloalkyl 1-6 3-11 groups, C alkoxy groups, C haloalkoxy groups, C alkylthio groups, C 1-6 1-6 1-6 1-6 haloalkylthio groups, C alkylsulfonyl groups, C haloalkylsulfonyl groups, C 1-6 1-6 1-6 alkoxycarbonyl groups, 4 to 7-membered non-aromatic heterocyclyl groups, mono-C alkylamino groups, di-C alkylamino groups, phenyl groups, 5 to 6-membered aromatic heterocyclyl groups, mono-C alkylaminosulfonyl groups and di-C alkylaminosulfonyl 1-6 1-6 groups), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (73) The compound according to (72), wherein R is a hydrogen atom, a phenyl group, a 5 to 10-membered aromatic heterocyclyl group or a 8 to 11-membered partially saturated aromatic cyclic group (the phenyl group, the 5 to 10-membered aromatic heterocyclyl group and the 8 to 11-membered partially saturated aromatic cyclic group are unsubstituted or substituted with one, two or three identical or different substituents independently selected from the group consisting of halogen atoms, cyano groups, nitro groups, C alkyl groups, C haloalkyl groups and C alkoxycarbonyl groups), a 1-3 1-3 1-6 tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (74) The compound according to (72), wherein R is a 4 to 7-membered non-aromatic 40 heterocyclyl group (the 4 to 7-membered non-aromatic heterocyclyl group is unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, halogen atoms, cyano groups, C alkyl groups (the C alkyl groups are unsubstituted or substituted 1-3 1-3 with a cyano group) and C haloalkyl groups), a tautomer or a pharmaceutically 45 acceptable salt of the compound or a solvate thereof. (75) The compound according to any one of (41) and (68) to (71), wherein L is represented by any of the following formulae (XIX -1) to (XIX -7): 1b 12b (wherein E is an oxygen atom, and R is a hydrogen atom or a C alkyl group (the C alkyl group is unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, cyano groups, hydroxy groups, C allkoxy groups, C cycloalkyl groups, 4 to 7-membered 1-3 3-6 non-aromatic heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups)), and R is a hydrogen atom, a C alkyl group, a C haloalkyl group (the C alkyl group 1-6 1-6 1-6 and the C haloalkyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of cyano groups, hydroxy groups, C alkoxy groups, C alkylthio groups, C alkylsulfonyl groups, C 1-6 1-6 1-6 3-6 cycloalkyl groups, 4 to 7-membered non-aromatic heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups (the C cycloalkyl groups, the 4 to 7-membered non-aromatic heterocyclyl groups, the phenyl groups and the 5 to 6- membered aromatic heterocyclyl groups are unsubstituted or substituted with one, two or three identical or different substituents independently selected from the group consisting of the substituent set V , mono-C alkylaminosulfonyl groups and di-C 1-6 1-6 alkylaminosulfonyl groups)), a C cycloalkyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group, a 5 to 6-membered aromatic heterocyclyl group or a 8 to 11-membered partially saturated aromatic cyclic group (the C cycloalkyl group, the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group, the 5 to 6- membered aromatic heterocyclyl group and the 8 to 11-membered partially saturated aromatic cyclic group are unsubstituted or substituted with one, two or three identical or different substituents independently selected from the group consisting of the substituent set V , mono-C alkylaminosulfonyl groups and di-C alkylaminosulfonyl 1-6 1-6 groups), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (76) The compound according to (75), wherein L is represented by any of the following formulae (XXXI -1) to (XXXI -5): ( XXXI ) 1b O 1b 12b b b b (XXXI -5 ) (XXXI -1 ) (XXXI -2 ) (XXXI -3 ) ( XXXI -4) 1b 12b (wherein E is an oxygen atom, and R is a hydrogen atom, a C alkyl group (the C 1-3 1- alkyl group is unsubstituted or substituted with a substituent selected from the group consisting of a cyano group, a hydroxy group, a C allkoxy group, a C cycloalkyl 1-3 3-6 group and a phenyl group) or C haloalkyl group), and R is a hydrogen atom, a C alkyl group, a C haloalkyl group (the C alkyl group 1-6 1-6 1-6 and the C haloalkyl group are unsubstituted or substituted with one or two identical or different substituent selected from the group consisting of hydroxy groups, cyano groups, C alkoxy groups, C cycloalkyl groups, 4 to 7-membered non-aromatic heterocyclyl 1-3 3-6 groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups (the C cycloalkyl groups, the 4 to 7-membered non-aromatic heterocyclyl groups, the phenyl groups and the 5 to 6-membered aromatic heterocyclyl groups are unsubstituted or substituted with a hydroxy group or a halogen atom)), a C cycloalkyl group, a 4 to 7- membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non- aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, halogen atoms, cyano groups, C alkyl groups, C haloalkyl groups and C 1-3 1-3 1-6 alkoxycarbonyl groups), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (77) The compound according to (75), wherein L is represented by the formula (XXXII ): (wherein R is a hydrogen atom, a C alkyl group (the C alkyl group is 1-3 1-3 unsubstituted or substituted with a substituent selected from the group consisting of a cyano group, a hydroxy group, a C allkoxy group, a C cycloalkyl group and a phenyl 1-3 3-6 group) or a C haloalkyl group), and R is a hydrogen atom, a C alkyl group, a C haloalkyl group (the C alkyl group 1-3 1-3 1-3 and the C haloalkyl group are unsubstituted or substituted with one or two identical or different substituent selected from the group consisting of hydroxy groups, cyano groups, C alkoxy groups, C cycloalkyl groups (the C cycloalkyl groups are unsubstituted 1-3 3-6 3-6 or substituted with a hydroxy groups), 4 to 7-membered non-aromatic heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups), a C cycloalkyl group or a 4 to 7-membered non-aromatic heterocyclyl group (the C cycloalkyl group and the 4 to 7-membered non-aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of C alkyl groups, C haloalkyl 1-3 1-3 groups and C alkoxycarbonyl groups), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (78) The compound according to any one of (41) or (68) to (77), wherein L is a single bond or a C alkylene group, and the ring B is cyclohexane or piperidine, a tautomer 40 or a pharmaceutically acceptable salt of the compound or a solvate thereof. b 3b (79) The compound according to any one of (41) to (78), wherein n is 0 or 1, and R is a C alkyl group, a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. (80) A JAK inhibitor containing the compound as defined in any one of (1) to (79), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof, as an active ingredient. (81) A preventive, therapeutic or improving agent for diseases against which inhibition of JAK is effective, which contains the JAK inhibitor as defined in (80). (82) A therapeutic agent for articular rheumatism, which contains the JAK inhibitor as defined in (80). (83) Medicament containing the compound as defined in any one of (1) to (79), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof, as an active ingredient.

The present invention has made it possible to provide novel tricyclic pyrimidine compounds and tricyclic pyridine compounds which have excellent JAK inhibitory action and are especially useful for prevention and treatment of autoimmune diseases, inflammatory diseases and allergic diseases.

Now, the present invention will be described in further detail.

The term 'comprising' as used in this specification and claims means 'consisting at least in part of'. When interpreting statements in this specification and claims which include the term 'comprising', other features besides the features prefaced by this term in each statement can also be present. Related terms such as 'comprise' and 'comprised' are to be interpreted in similar manner.

In the present invention, “n-” denotes normal, “i-” denotes iso, “s-” or "sec" denotes secondary, “t-” or “tert-” denotes tertiary, “c-” denotes cyclo, “o-” denotes ortho, “m-” denotes meta, “p-” denotes para, “cis-” denotes a cis isomer, “trans-” denotes a trans isomer, “(E)-” denotes a E isomer, “(Z)-” denotes a Z isomer, “rac” and “racemate” denotes racemate, “diastereomixture” denotes a mixture of diastereomers, “Ph” denotes phenyl, “Py” denotes pyridyl, “Me” denotes methyl, “Et” denotes ethyl, “Pr” denotes propyl, “Bu” denotes butyl, “Boc” denotes tertiary-butoxycarbonyl, “Cbz” denotes benzyloxycarbonyl, “Ms” denotes methanesulfonyl, “Tf” denotes trifluoromethanesulfonyl, “Ts” denotes p-toluenesulfonyl, “SEM” denotes [2- (trimethylsilyl)ethoxy]methyl, “TIPS” denotes triisopropylsilyl, “TBDPS” denotes tertiary- butyldiphenylsilyl, and “TBS” denotes tertiary-butyldimethylsilyl.

First, the terms used herein for description of chemical structures will be explained.

A “halogen atom” is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.

A “C alkyl group” is a methyl group, an ethyl group, a propyl group or an isopropyl group.

A “C alkyl group” is a linear or branched alkyl group containing one to six carbon atoms and may, for example, be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a t-butyl group, a n-pentyl group, n- hexyl group or the like. 40 A “C haloalkyl group” is a group derived from the above-mentioned C alkyl 1-3 1-3 group by replacing one or more hydrogen atom(s) at arbitrary position(s) by one or more identical or different halogen atoms selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms.

A “C haloalkyl group” is a group derived from the above-mentioned C alkyl 1-6 1-6 45 group by replacing one or more hydrogen atom(s) at arbitrary position(s) by one or more identical or different halogen atoms selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms.

A “C cycloalkane” is a monocyclic, fused, bridged or spiro aliphatic hydrocarbon 3-11 ring having 3 to 11 ring-constituting carbon atoms and may, for example, be cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, adamantane, bicyclo[3.1.0]octane, bicyclo[2.2.1]heptane, spiro[5.5]undecane or the like.

A “C cycloalkyl group” is a monovalent group derived from the above- 3-11 mentioned “C cycloalkane” by removing a hydrogen atom at an arbitrary position. 3-11 A “C cycloalkane” is a ring having 3 to 6 ring-constituting carbon atoms among the above-mentioned “C cycloalkane” and may, for example, be cyclopropane, 3-11 cyclobutane, cyclopentane, cyclohexane or the like.

A “C cycloalkyl group” is a group having 3 to 6 ring-constituting carbon atoms among the above-mentioned “C cycloalkyl group”, and may, for example, be a 3-11 cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group or the like.

A “C cycloalkane” is a ring having 4 to 7 ring-constituting carbon atoms among the above-mentioned “C cycloalkane” and may, for example, be cyclobutane, 3-11 cyclopentane, cyclohexane, cycloheptane or the like.

A “C cycloalkene” is a non-aromatic ring derived from replacing one or more 3-11 bonds in the above-mentioned “C cycloalkane” by double bond(s) and may, for 3-11 example, be cyclopropene, cyclobutene, cyclopentene, cyclohexene, cyclohexa-1,3- diene, cyclohexa-1,4-diene, bicyclo[2.2.1]hepta-2,5-diene, spiro[2.5]octene, 1,2,5,6- tetrahydronaphthalene or the like.

A “C alkenyl group” is a linear or branched alkenyl group having at least one double bond and 2 to 6 carbon atoms and may, for example be an ethenyl(vinyl) group, a 1-propenyl group, a 2-propenyl(allyl) group, an isopropenyl group, a 1-butenyl group, a 2-butenyl group, a 3-butenyl(homoallyl) group, a 4-pentenyl group, a 5-hexenyl group or the like.

A “C alkenyl group” is an ethenyl(vinyl) group, a 1-propenyl group, a 2- propenyl(allyl) group or an isopropenyl group.

A “C haloalkenyl group” is a group derived from the above-mentioned ”C 2-6 2-6 alkenyl group” by replacing one or more hydrogen atom(s) at arbitrary position(s) by one or more identical or different halogen atoms selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms.

A “C alkynyl group” is a linear or branched alkynyl group having at least one triple bond and 2 to 6 carbon atoms and may, for example be an ethynyl group, a 1- propynyl group, a 3-propynyl group, a 1-butynyl group, a 2-butynyl group, a 3-butynyl group, a 4-pentynyl group, a 5-hexynyl group, a 1,5-hexandiynyl group or the like.

A “C alkoxy group” is a linear or branched alkoxy group having 1 to 6 carbon atoms and may, for example, be a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group, an isobutoxy group, a t-butoxy group, a n- 40 pentyloxy group, a n-hexyloxy group or the like.

A “C alkoxy group” is a methoxy group, an ethoxy group, a n-propoxy group or an i-propoxy group.

A “C haloalkoxy group” is a group derived from the above-mentioned “C 1-6 1-6 alkoxy group” by replacing one or more hydrogen atom(s) at arbitrary position(s) by one 45 or more identical or different halogen atoms selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms.

A “C haloalkoxy group” is a group derived from the above-mentioned “C 1-3 1-3 alkoxy group” by replacing one or more hydrogen atom(s) at arbitrary position(s) by one or more identical or different halogen atoms selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms.

A “C alkylene group” is a bivalent group derived from the above-mentioned ”C 1-6 1-6 alkyl group” by removing a hydrogen atom at an arbitrary position and may, for example, be a methylene group, an ethylene group, a propane-1,3-diyl group, a propane-1,2-diyl group, a 2,2-dimethyl-propane-1,3-diyl group, a hexane-1,6-diyl group, or a 3- methylbutane-1,2-diyl group or the like.

A “C alkylene group” is a methylene group, an ethylene group, a propane-1,3- diyl group or a propane-1,2-diyl group.

A “C haloalkylene group” is a group derived from the above-mentioned ”C 1-6 1-6 alkylene group” by replacing one or more hydrogen atom(s) at arbitrary position(s) by one or more identical or different halogen atoms selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms.

A “C haloalkylene group” is a group derived from the above-mentioned ”C 1-3 1-3 alkylene group” by replacing one or more hydrogen atom(s) at arbitrary position(s) by one or more identical or different halogen atoms selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms.

A “C alkenylene group” is a bivalent group derived from the above- mentioned ”C alkenyl group” by removing a hydrogen atom at an arbitrary position and may, for example, be an ethenylene group, an ethene-1,1-diyl group, an ethane- 1,2-diyl group, a propene-1,1-diyl group, a propene-1,2-diyl group, a propene-1,3-diyl group, a butene-1,4-diyl group, a butene-1,3-diyl group, a butene-1,4-diyl group, a but-1,3-diene-1,4-diyl group, a pentene-1,5-diyl group, a hexene-1,6-diyl group, a hexa-2,4-diene-1,6-diyl group or the like.

A “C alkenylene group” is an ethene-1,1-diyl group, an ethane-1,2-diyl group, a propene-1,1-diyl group, a propene-1,2-diyl group, a propene-1,3-diyl group.

A “C alkynylene group” is a linear or branched alkynylene group having at least one triple bond and 2 to 6 carbon atoms and may, for example, be an ethyn-1,2-diyl group, a propyn-1,2-diyl group, a butyn-1,4-diyl group, a butyn-1,3-diyl group, a butyn-1,4-diyl group, a pentyn-1,5-diyl group, a pentyn-1,4-diyl group, a hex yn-1,6-diyl group or the like.

A “C aromatic carbocycle” is a monocyclic, bicyclic or tricyclic aromatic 6-14 carbocycle having 6 to 14 carbon atoms as the sole ring-constituting atoms and may, for example, be benzene, pentalene, naphthalene, azulene, anthracene, phenanthrene or the like.

A “C aryl group” is a monovalent group derived from the above-mentioned “C 6-14 6- aromatic carbocycle “ by removing a hydrogen atom and may have the free valence at any position without particular restriction. 40 A “5 to 10-membered aromatic heterocycle” is a monocyclic or fused aromatic heterocyclyl group having 5 to 10 ring-constituting atoms including 1 to 5 hetero atoms (such as nitrogen atoms, oxygen atoms and sulfur atoms) and may, for example, be furan, thiophene, pyrrole, imidazole, triazole, tetrazole, thiazole, pyrazole, oxazole, isoxazole, isothiazole, thiadiazole, oxadiazole, pyridine, pyrazine, pyridazine, pyrimidine, 45 triazine, purine, pteridine, quinoline, isoquinoline, naphthylidine, quinoxaline, cinnoline, quinazoline, phthalazine, imidazopyridine, imidazothiazole, imidazooxazole, benzothiazole, benzoxazole, benzimidazole, indole, isoindole, indazole, pyrrolopyridine, thienopyridine, furopyridine, benzothiadiazole, benzoxadiazole, pyridopyrimidine, benzofuran, benzothiophene, thienofuran or the like.

In the case of a “5 to 10-membered aromatic heterocycle” having a C=N double bond, it may be in the form of an N-oxide.

A “5 to 10-membered aromatic heterocyclyl group” is a monovalent group derived from the above-mentioned “5 to 10-membered aromatic heterocycle” by removing a hydrogen atom at an arbitrary position and may have the free valence at any position without particular restrictions.

A “5 to 6-membered aromatic heterocycle” is a monocyclic group having 5 to 6 ring-constituting atoms among the above-mentioned “5 to 10-membered aromatic heterocycles” and may, for example, be pyrrole, pyrazole, imidazole, triazole, tetrazole, pyridine, pyridazine, pyrimidine, pyrazine, triazine, furan, thiophene, thiazole, isothiazole, oxazole, isoxazole, oxadiazole, thiadiazole or the like.

A “5 to 6-membered aromatic heterocyclyl group” is a monovalent group derived from the above-mentioned “5 to 6-membered aromatic heterocycle” by removing a hydrogen atom at an arbitrary position and may have the free valence at any position without particular restrictions.

A “3 to 14-membered non-aromatic heterocycle” is a non-aromatic heterocycle: 1) which has 3 to 14 ring-constituting atoms, 2) the ring-constituting atoms of which contains 1 to 7 hetero atoms selected from nitrogen atoms, oxygen atoms or sulfur atoms, 3) which may have one or more carbonyl groups, one or more double or triple bonds in the ring system, 4) which may contain one or more sulfur atoms in the form of sulfinyl or sulfonyl groups as ring-constituting atoms, and ) which may be a monocyclic ring, a fused ring (in the fused ring, a non-aromatic ring may be fused to non-aromatic ring(s) or to aromatic-ring(s)), a bridged ring or a spiro ring. It may, for example, be azetidine, pyrrolidine, piperidine, azepane, azocane, tetrahydrofuran, tetrahydropyran, morpholine, thiomorpholine, piperazine, thiazolidine, 1,4-dioxane, imidazoline, thiazoline, benzopyran, isochroman, chroman, indoline, isoindoline, azaindane, tetrahydroazanaphthalene, azachroman, tetrahydrobenzofuran, tetrahydrobenzothiophene, 2,3,4,5-tetrahydro-benzo[b]thiophene, ,3,4-dihydro-2H- benzo[b][1,4]dioxepine, 6,7-dihydro-5H-cyclopenta[b]pyrazine, 5,6-dihydro-4H- cyclopenta[b]thiophene, 4,5,6,7-tetrahydrobenz[b]thiophene, 2,3-dihydroisoindolone, 3,4-dihydro-2H-isoquinolinone, 3,4-dihydro-2H-benzo[b]oxepinone, 2,3,4,4a,9,9a- hexahydro-1H-carbazole, 1’H-spiro[cyclopropane-1,2-quinoxalin]-3’(4’H)-one, 10H- phenoxazine, [1,3]dioxolo[4,5-f]quinoline or the like.

A “3 to 14-membered non-aromatic heterocyclyl group” is a monovalent group derived from the above-mentioned “3 to 14-membered non-aromatic heterocycle” by 40 removing a hydrogen atom at an arbitrary position. It may have the free valence at any position without particular restrictions, but in the case of an fused ring system consisting of a non-aromatic ring fused to an aromatic ring, it has the free valence in the non- aromatic ring.

A “3 to 11-membered non-aromatic heterocycle” is non-aromatic heterocycle: 45 1) which has 3 to 11 ring-constituting atoms 2) the ring-constituting atoms of which contains 1 to 5 hetero atoms selected from nitrogen atoms, oxygen atoms or sulfur atoms, 3) which may have one or more carbonyl groups, one or more double or triple bonds in the ring system, 4) which may contain one or more sulfur atoms in the form of sulfinyl or sulfonyl groups as ring-constituting atoms, and 5) which may be a monocyclic ring, a fused ring (in the fused ring, a non-aromatic ring may be fused to non-aromatic ring(s) or to aromatic-ring(s)), a bridged ring or a spiro ring. It may, for example, be azetidine, pyrrolidine, piperidine, azepane, azocane, tetrahydrofuran, tetrahydropyran, morpholine, thiomorpholine, piperazine, thiazolidine, 1,4-dioxane, imidazoline, thiazoline, benzopyran, isochroman, chroman, indoline, isoindoline, azaindane, tetrahydroazanaphthalene, azachroman, tetrahydrobenzofuran, tetrahydrobenzothiophene, 2,3,4,5-tetrahydro-benzo[b]thiophene, 3,4-dihydro-2H- benzo[b][1,4]oxepine, 6,7-dihydro-5H-cyclopenta[b]pyrazine, 5,6-dihydro-4H- cyclopenta[b]thiophene, 4,5,6,7-tetrahydrobenzo[b]thiophene, 2,3-dihydroisoindolone, 3,4-dihydro2H-isoquinolinone, 3,4-dihydro2H-benzo[b]oxepinone or the like.

A 3 to 11-membered non-aromatic heterocyclyl group” is a monovalent group derived from the above-mentioned “3 to 11-membered non-aromatic heterocycle” by removing a hydrogen atom at an arbitrary position. It may have the free valence at any position without particular restrictions, but in the case of an fused ring system consisting of a non-aromatic ring fused to an aromatic ring, it has the free valence in the non- aromatic ring.

A “4 to 7-membered non-aromatic heterocycle” is a monocyclic non-aromatic heterocycle: 1) which has 4 to 7 ring-constituting atoms 2) the ring-constituting atoms of which contains 1 to 3 hetero atoms selected from nitrogen atoms, oxygen atoms and sulfur atoms, 3) which may have one or more carbonyl groups, one or more double or triple bonds in the ring system, and 4) which may contain one or more sulfur atoms in the form of sulfinyl or sulfonyl groups as ring-constituting atoms. It may, for example, be azetidine, pyrrolidine, pyrrolidinone, oxazolidine, isoxazolidine, thiazolidine, isothiazolidine, piperazine, piperazinone, piperidine, piperidinone, morpholine, thiomorpholine, azepine, diazepine, oxetane, tetrahydrofuran, 1,3-dioxorane, tetrahydropyran, 1,4-dioxane, oxepane, homomorpholine or the like.

A “4 to 7-membered non-aromatic heterocyclyl group” is a monovalent group derived from the above-mentioned “4 to 7-membered non-aromatic heterocycle” by removing a hydrogen atom at an arbitrary position and may have the free valence at any position without particular restrictions.

A “C alkylthio group” is a group consisting of the above-mentioned “C alkyl 1-6 1-6 group” attached to a sulfur atom and may, for example, be a methylthio group, an 40 ethylthio group, a n-propylthio group, an isopropylthio group, a n-butylthio group, an isobutylthio group, a t-butylthio group, a n-pentylthio group, a n-hexylthio group or the like.

A “C alkylthio group” is a group consisting of the above-mentioned “C alkyl 1-3 1-3 group” attached to a sulfur atom and may, for example, be a methylthio group, an 45 ethylthio group, a n-propylthio group or an isopropylthio group.

A “C haloalkylthio group” is a group derived from the above-mentioned “C 1-6 1-6 alkylthio group” by replacing one or more hydrogen atom(s) at arbitrary position(s) by one or more identical or different halogen atoms selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms.

A “C haloalkylthio group” is a group derived from the above-mentioned “C 1-3 1-3 alkylthio group” by replacing one or more hydrogen atom(s) at arbitrary position(s) by one or more identical or different halogen atoms selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms.

A “C alkylsulfonyl group” is a group consisting of the above-mentioned ”C 1-6 1-6 alkyl group” attached to a sulfonyl group and may, for example, be a methylsulfonyl group, an ethylsulfonyl group, a n-propylsulfonyl group, an isopropylsulfonyl group, a n- butylsulfonyl group, an isobutylsulfonyl group, a t-butylsulfonyl group, a n-pentylsulfonyl group, a n-hexylsulfonyl group or the like.

A “C alkylsulfonyl group” is a group consisting of the above-mentioned “C 1-3 1-3 alkyl group” attached to a sulfonyl group and may, for example, be a methylsulfonyl group, an ethylsulfonyl group, a n-propylsulfonyl group or an isopropylsulfonyl group.

A “C haloalkylsulfonyl group” is a group derived from the above-mentioned “C 1-6 1-6 alkylsulfonyl group” by replacing one or more hydrogen atom(s) at arbitrary position(s) by one or more identical or different halogen atoms selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms.

A “C haloalkylsulfonyl group” is a group derived from the above-mentioned “C 1-3 1-3 alkylsulfonyl group” by replacing one or more hydrogen atom(s) at arbitrary position(s) by one or more identical or different halogen atoms selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms.

A “C alkoxycarbonyl group” is a group consisting of the above-mentioned ”C 1-6 1-6 alkoxy group” attached to a carbonyl group and may, for example, be a methoxycarbonyl group, an ethoxycarbonyl group, a n-propoxycarbonyl group, an isopropoxycarbonyl group, a n-butoxycarbonyl group, an isobutoxycarbonyl group, a t- butoxycarbonyl group, a n-pentyloxycarbonyl group, a n-hexyloxycarbonyl group or the like.

A “C alkoxycarbonyl group” is a methoxycarbonyl group, an ethoxycarbonyl group, a n-propoxycarbonyl group or an isopropoxycarbonyl group.

A “mono-C alkylamino group” is a group consisting of the above-mentioned “C 1-6 1-6 alkyl group” attached to an amino group and may, for example, be a methylamino group, an ethylamino group, a n-propylamino group, an isopropylamino group, a n-butylamino group, an isobutylamino group, a t-butylamino group, a n-pentylamino group, a n- hexylamino group or the like.

A “mono-C alkylamino group” is a methylamino group, an ethylamino group, a n- propylamino group or an isopropylamino group.

A “di-C alkylamino group” is a group consisting of an amino group attached to two identical or different ”C alkyl groups” such as those mentioned above and may, for 40 example, be a dimethylamino group, a diethylamino group, a di-n-propylamino group, a diisopropylamino group, a di-n-butylamino group, a diisobutylamino group, a di-t- butylamino group, a di-n-pentylamino group, a di-n-hexylamino group, an N-ethyl-N- methylamino group, an N-methyl-N-n-propylamino group, an N-isopropyl-N- methylamino group, an N-n-butyl-N-methylamino group, an N-isobutyl-N-methylamino 45 group, an N-t-butyl-N-methylamino group, an N-methyl-N-n-pentylamino group, N-n- hexyl-N-methylamino group, an N-ethyl-N-n-propylamino group, an N-ethyl-N- isopropylamino group, an N-n-butyl-N-ethylamino group, an N-ethyl-N-isobutylamino group, an N-t-butyl-N-ethylamino group, an N-ethyl-N-n-pentylamino group, an N-ethyl- N-n-hexylamino group or the like.

A “di-C alkylamino group” is a dimethylamino group, a diethylamino group, a di- n-propylamino group, a diisopropylamino group, an N-ethyl-N-methylamino group, an N- methyl-N-n-propylamino group, an N-isopropyl-N-methylamino group, an N-ethyl-N-n- propylamino group or an N-ethyl-N-isopropylamino group.

A “C alkylcarbonyl group” is a group consisting of the above-mentioned “C 1-6 1-6 alkyl group” attached to a carbonyl group and may, for example, be an acetyl group, a propionyl group, a butyryl group, an isobutyryl group, a pentanoyl group, a 3- methylbutanoyl group, a pivaloyl group, a hexanoyl group or a heptanoyl group.

A “C alkylcarbonyl group” is an acetyl group, a propionyl group, a butyryl group or an isobutyryl group.

A “C haloalkylcarbonyl group” is a group derived from the above-mentioned “C 1-6 1- alkylcarbonyl group” by replacing one or more hydrogen atom(s) at arbitrary position(s) by one or more identical or different halogen atoms selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms.

A “C haloalkylcarbonyl group” is a group derived from the above-mentioned “C 1-3 1- alkylcarbonyl group” by replacing one or more hydrogen atom(s) at arbitrary position(s) by one or more identical or different halogen atoms selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms.

A “mono-C alkylaminocarbonyl group” is a group consisting of the above- mentioned “mono-C alkylamino group” attached to a carbonyl group and may, for example, be a methylaminocarbonyl group, an ethylaminocarbonyl group, a n- propylaminocarbonyl group, an isopropylaminocarbonyl group, a n-butylaminocarbonyl group, an isobutylaminocarbonyl group, a t-butylaminocarbonyl group, a n- pentylaminocarbonyl group, a n-hexylaminocarbonyl group or the like.

A “mono-C alkylaminocarbonyl group” is a methylaminocarbonyl group, an ethylaminocarbonyl group, a n-propylaminocarbonyl group or an isopropylaminocarbonyl group.

A “di-C alkylaminocarbonyl group” is a group consisting of the above-mentioned “di-C alkylamino group” attached to a carbonyl group and may, for example, be a dimethylaminocarbonyl group, a diethylaminocarbonyl group, a di-n- propylaminocarbonyl group, a diisopropylaminocarbonyl group, a di-n- butylaminocarbonyl group, a diisobutylaminocarbonyl group, a di-t-butylaminocarbonyl group, a di-n-pentylaminocarbonyl group, a di-n-hexylaminocarbonyl group, an N-ethyl- N-methylaminocarbonyl group, an N-methyl-N-n-propylaminocarbonyl group, an N- isopropyl-N-methylaminocarbonyl group, an N-n-butyl-N-methylaminocarbonyl group, an N-isobutyl-N-methylaminocarbonyl group, an N-t-butyl-N-methylaminocarbonyl group, an N-methyl-N-n-pentylaminocarbonyl group, an N-n-hexyl-N-methylaminocarbonyl 40 group, an N-ethyl-N-n-propylaminocarbonyl group, an N-ethyl-N- isopropylaminocarbonyl group, an N-n-butyl-N-ethylaminocarbonyl group, an N-ethyl-N- isobutylaminocarbonyl group, an N-t-butyl-N-ethylaminocarbonyl group, an N-ethyl-N-n- pentylaminocarbonyl group, an N-ethyl-N-n-hexylaminocarbonyl group or the like.

A “di-C alkylaminocarbonyl group” is a dimethylaminocarbonyl group, a 45 diethylaminocarbonyl group, a di-n-propylaminocarbonyl group, a diisopropylaminocarbonyl group, an N-ethyl-N-methylaminocarbonyl group, an N- methyl-N-n-propylaminocarbonyl group, an N-isopropyl-N-methylaminocarbonyl group, N-ethyl-N-n-propylaminocarbonyl group, or an N-ethyl-N-isopropylaminocarbonyl group.

A “C alkylcarbonylamino group” is a group consisting of the above-mentioned “C alkylcarbonyl group” attached to an amino group and may, for example, be a methylcarbonylamino group, an ethylcarbonylamino group, a n-propylcarbonylamino group, an isopropylcarbonylamino group, a n-butylcarbonylamino group, an isobutylcarbonylamino group, a t-butylcarbonylamino group, a n-pentylcarbonylamino group, a n-hexylcarbonylamino group or the like.

A “C alkylcarbonylamino group” is a methylcarbonylamino group, an ethylcarbonylamino group, a n-propylcarbonylamino group or an isopropylcarbonylamino group.

A “mono-C alkylaminosulfonyl group” is a group consisting of the above- mentioned “mono-C alkylamino group” attached to a sulfonyl group and may, for example, be a methylaminosulfonyl group, an ethylaminosulfonyl group, a n- propylaminosulfonyl group, an isopropylaminosulfonyl group, a n-butylaminosulfonyl group, an isobutylaminosulfonyl group, a t-butylaminosulfonyl group, a n- pentylaminosulfonyl group, a n-hexylaminosulfonyl group or the like.

A “mono-C alkylaminosulfonyl group” is a methylaminosulfonyl group, an ethylaminosulfonyl group, a n-propylaminosulfonyl group or an isopropylaminosulfonyl group.

A “di-C alkylaminosulfonyl group” is a group consisting of the above-mentioned “di-C alkylamino group” attached to a sulfonyl group and may, for example, be a dimethylaminosulfonyl group, a diethylaminosulfonyl group, a di-n-propylaminosulfonyl group, a diisopropylaminosulfonyl group, a di-n-butylaminosulfonyl group, a diisobutylaminosulfonyl group, a di-t-butylaminosulfonyl group, a di-n- pentylaminosulfonyl group, a di-n-hexylaminosulfonyl group, an N-ethyl-N- methylaminosulfonyl group, an N-methyl-N-n-propylaminosulfonyl group, an N- isopropyl-N-methylaminosulfonyl group, an N-n-butyl-N-methylaminosulfonyl group, an N-isobutyl-N-methylaminosulfonyl group, an N-t-butyl-N-methylaminosulfonyl group, an N-methyl-N-n-pentylaminosulfonyl group, N-n-hexyl-N-methylaminosulfonyl group, an N-ethyl-N-n-propylaminosulfonyl group, an N-ethyl-N-isopropylaminosulfonyl group, an N-n-butyl-N-ethylaminosulfonyl group, an N-ethyl-N-isobutylaminosulfonyl group, an N-t- butyl-N-ethylaminosulfonyl group, an N-ethyl-N-n-pentylaminosulfonyl group, an N- ethyl-N-n-hexylaminosulfonyl group or the like.

A “di-C alkylaminosulfonyl group” is a dimethylaminosulfonyl group, a diethylaminosulfonyl group, a di-n-propylaminosulfonyl group, a diisopropylaminosulfonyl group, an N-ethyl-N-methylaminosulfonyl group, an N-methyl- N-n-propylaminosulfonyl group, an N-isopropyl-N-methylaminosulfonyl group, an N- ethyl-N-n-propylaminosulfonyl group, or an N-ethyl-N-isopropylaminosulfonyl group or an N-isopropyl-N-n-propylaminosulfonyl group. 40 A “C alkylsulfonylamino group” is a group consisting of the above- mentioned ”C alkylsulfonyl group” attached to an amino group and may, for example, be a methylsulfonylamino group, an ethylsulfonylamino group, a n-propylsulfonylamino group, an isopropylsulfonylamino group, a n-butylsulfonylamino group, an isobutylsulfonylamino group, a t-butylsulfonylamino group, a n-pentylsulfonylamino 45 group, a n-hexylsulfonylamino group or the like.

A “C alkoxycarbonylamino group” is a group consisting of the above- mentioned ”C alkoxycarbonyl group” attached to an amino group and may, for example, be a methoxycarbonylamino group, an ethoxycarbonylamino group, a n- propoxycarbonylamino group, an isopropoxycarbonylamino group, a n- butoxycarbonylamino group, an isobutoxycarbonylamino group, a t- butoxycarbonylamino group, a n-pentyloxycarbonylamino group, a n- hexyloxycarbonylamino group or the like.

A “C cycloalkoxy group” is a group consisting of the above-mentioned ”C 3-6 3-6 cycloalkyl group” attached to an oxygen atom and may, for example, be a cyclopropoxy group, a cyclobutoxy group, a cyclopentyloxy group, a cyclohexyloxy group or the like.

A “C cycloalkylamino group” is a group consisting of the above-mentioned ”C 3-6 3-6 cycloalkyl group” attached to an amino group and may, for example, be a cyclopropylamino group, a cyclobutylamino group, a cyclopentylamino group, a cyclohexylamino group or the like.

A “di-C cycloalkylamino group” is a group consisting of an amino group attached to two identical or different “C cycloalkyl groups” such as those mentioned above and may, for example, be a dicyclopropylamino group, a dicyclobutylamino group, a dicylopentylamino group, a dicyclohexylamino group or the like.

A “C cycloalkylthio group” is a group consisting of the ”C cycloalkyl group” 3-6 3-6 attached to -S- and may, for example, be a cyclopropylthio group, a cyclobutylthio group, a cyclopentylthio group, a cyclohexylthio group or the like.

A “C cycloalkylcarbonyl group” is a group consisting of the above-mentioned “C cycloalkyl group” attached to a carbonyl group and may, for example, be a cyclopropylcarbonyl group, a cyclobutylcarbonyl group, a cyclopentylcarbonyl group, a cyclohexylcarbonyl group or the like.

A “C cycloalkylsulfonyl group” is a group consisting of the above-mentioned ”C 3-6 3- cycloalkyl group” attached to a sulfonyl group and may, for example, be a cyclopropylsulfonyl group, a cyclobutylsulfonyl group, a cyclopentylsulfonyl group, a cyclohexylsulfonyl group or the like.

A “8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon” is a fused ring system: 1) which has 8 to 14 ring-constituting atoms, 2) all the ring-constituting atoms of which are carbon atoms, 3) which may have one or more carbonyl groups, one or more double or triple bonds in the ring system, and 4) which consists of non-aromatic ring(s) fused to aromatic-ring(s). It may, for example, be 1H-indene, 2,3-dihydroindene, 1H-indenon, 1,2-dihydronaphthalene, 1,2,3,4- tetrahydronaphthalene, 3,4-dihydronaphthalen-1(2H)-on, 1,2,3,4-tetrahydro-1,4- methanonaphthalene, 1,2,3,4-tetrahydrophenanthrene, 2,3-dihydro-1H-phenalene, 9H- fluorene or the like.

A “8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon group” is a 40 monovalent group derived from the above-mentioned “8 to 14-membered aromatic ring- condensed alicyclic hydrocarbon” by removing a hydrogen atom at an arbitrary position.

It may have the free valence at any position in the alicyclic carbocycle without particular restrictions.

It may, for example, be a 1H-indenyl group, a 1H-indenyl group, a 1H-inden- 45 3-yl group, a 1,2,3,4-tetrahydronaphthalenyl group, a 1,2,3,4-tetrahydronaphthalen yl group, a 1,2,3,4-tetrahydronaphthalenyl group, a 1,2,3,4-tetrahydronaphthalenyl group, a 4-oxo-1,2,3,4-tetrahydronaphthalenyl group, a 9H-fluorenyl group or the like.

A “8 to 14-membered partially saturated aromatic cyclic group” is a group derived from 1) a bicyclic or tricyclic ring having 8 to 14 ring-constituting atoms and consisting of a non-aromatic ring fused to aromatic rings among the above-mentioned “3 to 14- menbered non-aromatic heterocycle ” or 2) the above-mentioned “8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon” by removing a hydrogen atom at an arbitrary position. It may have the free valence at any position in the aromatic ring without particular restrictions.

It may, for example, be a 1H-indenyl group, a 1H-indenyl group, a 1H-inden- 6-yl group, a 1H-indenyl group, a 5,6,7,8-tetrahydronaphthalenyl group, a 5,6,7,8- tetrahydronaphthalenyl group, a 5,6,7,8-tetrahydronaphthalenyl group, a 5,6,7,8- tetrahydronaphthalenyl group, a 9H-fluorene2-yl group, an indolinyl group, an indolinyl group, an indolinyl group, an indolinyl group, a chromanyl group, a chromanyl group, a chromanyl group, a chromanyl group, a 4,5,6,7- tetrahydrobenzo[b]thiophenyl group, a 2,3,4,4a,9,9a-hexahydro-1H-carbazolyl group or the like.

A “8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon” is a fused ring system: 1) which has 8 to 11 ring-constituting atoms, 2) all the ring-constituting atoms of which are carbon atoms, 3) which may have one or more carbonyl groups, one or more double or triple bonds in the ring system, and 4) which consists of an alicyclic hydrocarbon fused to a benzene ring, and it may, for example, be 1H-indene, 2,3-dihydroindene, 1H-indenon, 1,2-dihydronaphthalene, 1,2,3,4-tetrahydronaphthalene, 3,4-dihydronaphthalen-1(2H)-one or the like.

A “8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon group” is a group derived from the above-mentioned “8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon” by removing a hydrogen atom at an arbitrary position. and may have the free valence at any position in the alicyclic carbocycle without particular restrictions.

It may, for example, be a 1H-indenyl group, a 1H-indenyl group, a 1H-inden- 6-yl group, a 1H-indenyl group, a 5,6,7,8-tetrahydronaphthalenyl group, a 5,6,7,8- tetrahydronaphthalenyl group, a 5,6,7,8-tetrahydronaphthalenyl group, a 5,6,7,8- tetrahydronaphthalenyl group or the like.

A “8 to 11-membered partially saturated aromatic cyclic group” is a group derived from 1) a partially saturated aromatic ring having 8 to 11 ring-constituting atoms and consisting of an aromatic ring fused to a non-aromatic ring among the above-mentioned "3 to 11 membered non-aromatic heterocycle" or 2) the above-mentioned “8 to 11- membered aromatic ring-condensed alicyclic hydrocarbon” by removing a hydrogen 40 atom at an arbitrary position. and may have the free valence at any position in the aromatic ring without particular restrictions.

It may, for example, be a 1H-indenyl group, a 1H-indenyl group, a 1H-inden- 6-yl group, a 1H-indenyl group, a 5,6,7,8-tetrahydronaphthalenyl group, a 5,6,7,8- tetrahydronaphthalenyl group, a 5,6,7,8-tetrahydronaphthalenyl group, a 5,6,7,8- 45 tetrahydronaphthalenyl group, an indolinyl group, an indolinyl group, an indolin- 6-yl group, an indolinyl group, a chromanyl group, a chromanyl group, a chromanyl group, a chromanyl group, 4,5,6,7-tetrahydrobenzo [b]thiophenyl group or the like.

Now, the tricyclic pyrimidine compounds of the present invention represented by the formula (I ) will be described.

First, how the ring A is fused in the tricyclic pyrimidine compounds of the present invention will be described.

As is indicated in the formula (I ), the ring A is fused to the pyrimidine ring so as to have a carbon atom and a nitrogen atom in common and attached to L via a carbon atom in the ring A in the formula (I ). 2a 2a (R ) a ( I ) Therefore, when the ring A is represented by the formula (II -1), ( II -1 ) the molecule as a whole is represented by the formula (I )-2: 2a 2a 1a a 3a a (R ) Y (I )- 2 and when the ring A is represented by the formula (II -2), (II -2 ) the molecule as a whole is represented by the formula (I )-3. a a a E N L B 3a a (R ) (I )- 3 In the present invention, the formulae representing L indicate that the left ends of 2a 2a the formulae are bonded to L , and the right ends of the formulae are bonded to R . 1a 2a 3a a In the present invention, L , L and R may be bounded to the ring B in the formula (I ) at any positions of the ring B without any particular restrictions.

Next, preferred structures of the respective substituents will be mentioned.

A preferred embodiment of the substituent R is a hydrogen atom or a halogen atom.

A more preferred embodiment of the substituent R is a hydrogen atom. a 10a 10a A preferred embodiment of the substituent Y is CR (wherein R is a hydrogen atom, a halogen atom, a cyano group, a C alkyl group, a C haloalkyl group or a C 1-6 1-6 3-6 cycloalkyl group). a 10a 10a A more preferred embodiment of the substituent Y is CR (wherein R is a hydrogen atom). a 9a 9a A preferred embodiment of the substituent X is CR (wherein R is a hydrogen atom, a halogen atom, a cyano group, a C alkyl group, a C haloalkyl group or a C 1-6 1-6 3-6 cycloalkyl group) or a nitrogen atom. a 9a 9a A more preferred embodiment of the substituent X is CR (wherein R is a hydrogen atom). a 9a 9a Another more preferred embodiment of the substituent X is CR (wherein R is a halogen atom).

A preferred embodiment of the ring A is represented by any of the following formulae (VII -1) to (VII -4): N 2a ( VII ) a a a a (VII -1 ) (VII -2 ) (VII -3 ) (VII -4 ) 2a 4a 7a 8a (wherein E is an oxygen atom or a sulfur atom, each of R , R and R is independently a hydrogen atom, an amino group, a carbamoyl group, a halogen atom, a cyano group, a C alkyl group, a C alkoxy group, a C alkylthio group, a C 1-6 1-6 1-6 1-6 alkylsulfonyl group (the C alkyl group, the C alkoxy group, the C alkylthio group 1-6 1-6 1-6 and the C alkylsulfonyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a C cycloalkyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 6- membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set 1a 6a V ), and R is a hydrogen atom, a C alkyl group (the C alkyl group is 1-6 1-6 unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a C cycloalkyl group, a 4 to 7- membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non- 40 aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V )).

A more preferred embodiment of the ring A is represented by any of the following formulae (IV -1) to (IV -3): N 2a (IV ) a a a ( IV -1 ) ( IV -2 ) (IV -3 ) 2a 4a (wherein E is an oxygen atom or a sulfur atom, R is a hydrogen atom, a halogen atom, a C alkyl group, a C alkoxy group, a C alkylthio group or a C alkylsulfonyl 1-3 1-3 1-3 1-3 group, and R is a hydrogen atom or a C alkyl group).

A further preferred embodiment of the ring A is represented by any of the following formulae (VIII -1) to (VIII -5).

N N N N H C O S ( VIII ) N N N N a a a (VIII -4 ) (VIII -5 ) (VIII -1 ) (VIII -2 ) (VIII -3 ) A particularly preferred embodiment of the ring A is represented by the formula (XXX ).

( XXX ) A preferred embodiment of he substituent L is a single bond or a C alkylene group.

A more preferred embodiment of the substituent L is a single bond or a methylene group.

A further preferred embodiment of the substituent L is a single bond.

A preferred embodiment of the ring B is a C cycloalkane, a 3 to 11-membered 3-11 non-aromatic heterocycle, a C aromatic carbocycle or a 5 to 10-membered aromatic 6-14 heterocycle.

Another preferred embodiment of the ring B is a C cycloalkane (a ring- 3-11 constituting methylene group of the C cycloalkane and the C cycloalkene is 3-11 3-11 replaced by a carbonyl group).

A more preferred embodiment of the ring B is a C cycloalkane, a 4 to 7- membered non-aromatic heterocycle, benzene or a 5 to 6-membered aromatic heterocycle.

Another more preferred embodiment of the ring B is a C cycloalkane (a ring- constituting methylene group of the C cycloalkane is replaced by a carbonyl group).

Another more preferred embodiment of the ring B is spiro[2,5]octane or adamantane.

A further preferred embodiment of the ring B is azetidine, pyrrolidine, piperidine, azepane, cyclobutane, cyclopentane, cyclohexane, bicyclo[2.2.1]heptane, cycloheptane or benzene.

Another further preferred embodiment of the ring B is cyclohexanone.

A particularly preferred embodiment of the ring B is cyclohexane or piperidine.

A preferred embodiment of the substituent L is a single bond, a C alkylene group or a C haloalkylene group (the C alkylene group and the C haloalkylene 1-3 1-3 1-3 group are substituted with a cyano group).

Another preferred embodiment of the substituent L is a C alkylene group or a C haloalkylene group (the C alkylene group and the C haloalkylene group are 1-3 1-3 1-3 unsubstituted or substituted with a hydroxy group).

Another preferred embodiment of the substituent L is a C alkenylene group (the C alkenylene group is unsubstituted or substituted with a hydroxy group or a cyano group).

Another preferred embodiment of the substituent L is a C alkylene group or a C alkenylene group (the C alkylene group and the C alkenylene group are 2-3 1-3 2-3 substituted with two cyano groups).

Another preferred embodiment of the substituent L is a C alkylene group or a C alkenylene group (the C alkylene group and the C alkenylene group are 2-6 1-6 2-6 unsubstituted or substituted with one or two cyano groups) or a C haloalkylene. 2a 15a 15a Another preferred embodiment of the substituent L is =C(R )- (wherein R is a 2a a hydrogen atom or a cyano group, and the bond connecting the ring B and L is a 15a 15a double bond) or =C(R )-CH - (wherein R is a cyano group, and the bond connecting a 2a the ring B and L is a double bond).

A more preferred embodiment of the substituent L is a single bond or a methylene group (the methylene group is unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms or with a hydroxy group).

Another more preferred embodiment of the substituent L is an ethylene group (the ethylene group is unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms or with a hydroxy group) or a propylene group.

Another more preferred embodiment of the substituent L is a C alkylene group (the C alkylene group is substituted with a cyano group).

Another more preferred embodiment of the substituent L is a C alkylene group (the C alkylene group is substituted with two cyano groups). 40 Another more preferred embodiment of the substituent L is a C alkenylene group (the C alkenylene group is substituted with a cyano group).

Another more preferred embodiment of the substituent L is a C alkenylene group (the C alkenylene group is substituted with two cyano groups).

A further preferred embodiment of the substituent L is a single bond or a 45 methylene group.

Another further preferred embodiment of the substituent L is a C alkylene group (the C alkylene group is substituted with one or two cyano groups). 3a 2a A preferred embodiment of the substituent L and the substituent R is such that 3a 2a L is a single bond, and R is a hydrogen atom, a halogen atom, a C cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to -membered aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11- membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 10- membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ). 3a 2a Another preferred embodiment of the substituent L and the substituent R is 3a 2a such that L is a single bond, and R is a hydrogen atom, a halogen atom, an azido group, a C cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 10-membered aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 10-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group 4a 9a consisting of the substituent set V , the substituent set V and C alkyl groups (the C alkyl groups are substituted with a C alkoxycarbonylamino group (the C 1-6 1-6 1-6 alkoxycarbonylamino group is unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms))). 3a 2a Another preferred embodiment of the substituent L and the substituent R is 3a 2a such that L is a single bond, and R is a 8 to 11-membered partially saturated aromatic cyclic group (the 8 to 11-membered partially saturated aromatic cyclic group is unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ). 3a 2a Another preferred embodiment of the substituent L and the substituent R is 3a a a such that L is represented by any of the following formulae (V -1) to (V -11): 12 1a R 12 E 1a a E O O a a a a a (V -1 ) (V -2 ) (V -3 ) (V -4 ) (V -5 ) (V -6 ) (V ) 12a 13a R a a 12 13 R R 12 a a a a a (V -7 ) (V -8 ) (V -9 ) (V -10 ) (V -11 ) 1a 12a 13a (wherein E is an oxygen atom or a sulfur atom, and each of R and R is independently a hydrogen atom , a C alkyl group or a C haloalkyl group), and R is 1-6 1-6 a hydrogen atom, a C alkyl group (the C alkyl group is unsubstituted or substituted 1-6 1-6 with one or more identical or different substituents independently selected from the substituent set V ), a C alkenyl group, a C cycloalkyl group, a 3 to 11-membered 2-6 3-6 non-aromatic heterocyclyl group, a phenyl group or a 5 to 10-membered aromatic heterocyclyl group (the C alkenyl group, the C cycloalkyl group, the 3 to 11- 2-6 3-6 membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 10- membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ). 3a 2a Another preferred embodiment of the substituent L and the substituent R is 3a a a such that L is represented by any of the following formulae (XIV -1) to (XIV -15) and (XIII ): R 12a a a a a a (XIV -1 ) (XIV -2 ) ( XIV -3 ) ( XIV -4 ) (XIV -5 ) (XIV ) N N O N 12a 13a R 12a 13a 12a a a a a a (XIV -6 ) ( XIV -7 ) ( XIV -8 ) (XIV -9 ) ( XIV -10 ) 1a 1a O O N S N O R 12a a a a a a ( XIV -11 ) ( XIV -12 ) (XIV -13 ) ( XIV -14 ) ( XIV -15 ) 1a 11a 11a (wherein E is an oxygen atom, a sulfur atom or NR (wherein R is a hydroxy 12a 13a group), and each of R and R is independently a hydrogen atom, a C alkyl group or a C haloalkyl group), and R is a hydrogen atom, a C alkyl group, a C alkenyl 1-6 1-6 2-6 group, a C alkynyl group (the C alkyl group, the C alkenyl group and the C 2-6 1-6 2-6 2-6 alkynyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V and the substituent set V ), a C cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a 3-11 phenyl group, a naphthyl group, a 5 to 10-membered aromatic heterocyclyl group, a 8 to 11-membered partially saturated aromatic cyclic group or a 8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon group (the C cycloalkyl group, the 3 to 11- 3-11 membered non-aromatic heterocyclyl group, the phenyl group, the naphthyl group, the 5 to 10-membered aromatic heterocyclyl group, the 8 to 11-membered partially saturated aromatic cyclic group and the 8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V and the substituent set V ). 3a 2a Another preferred embodiment of the substituent L and the substituent R is 3a a such that L is represented by the formula (X -9): , and R is a hydrogen atom. 3a 2a Another preferred embodiment of the substituent L and the substituent R is 3a a a such that L is represented by any of the following formulae (XXVI -1) to (XXVI -5): 1a 12a (wherein E is an oxygen atom or a sulfur atom, and R is a C alkyl group or a C 1-6 1-6 haloalkyl group (the C alkyl group and the C haloalkyl group is substituted with one 1-6 1-6 or two identical or different substituents independently selected from the group consisting of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, halogen atoms, cyano groups, nitro groups, C alkoxy groups, C 1-6 1-6 haloalkoxy groups, C alkylthio groups, C haloalkylthio groups, C alkylcarbonyl 1-6 1-6 1-6 groups, C haloalkylcarbonyl groups, C alkylsulfonyl groups, C haloalkylsulfonyl 1-6 1-6 1-6 groups, C alkoxycarbonyl groups, mono-C alkylamino groups, di-C alkylamino 1-6 1-6 1-6 groups, mono-C alkylaminocarbonyl groups, di-C alkylaminocarbonyl groups, C 1-6 1-6 1-6 alkylcarbonylamino groups, C cycloalkyl groups, 3 to 11-membered non-aromatic 3-11 heterocyclyl groups, C aryl groups and 5 to 10-membered aromatic heterocyclyl 6-14 groups (the C cycloalkyl groups, the 3 to 11-membered non-aromatic heterocyclyl 3-11 groups, the C aryl groups and the 5 to 10-membered aromatic heterocyclyl groups 6-14 are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V )), a C cycloalkyl group, a 3 to 11- 3-11 membered non-aromatic heterocyclyl group, a C aryl group or a 5 to 10-membered 6-14 aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11-membered non- 3-11 aromatic heterocyclyl group, the C aryl group and the 5 to 10-membered aromatic 6-14 heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V )), and R is a C alkyl group, a C alkenyl group, a C alkynyl group (the C alkyl group, 1-6 2-6 2-6 1-6 the C alkenyl group and the C alkynyl group are unsubstituted or substituted with 2-6 2-6 one or more identical or different substituents independently selected from the 6a 9a substituent set V and the substituent set V ), a C cycloalkyl group, a 3 to 11- membered non-aromatic heterocyclyl group, a phenyl group, a naphthyl group or a 5 to -membered aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11- membered non-aromatic heterocyclyl group, the phenyl group, the naphthyl group and the 5 to 10-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the 4a 9a substituent set V and the substituent set V ). 3a 2a A more preferred embodiment of the substituent L and the substituent R is 3a 2a such that L is a single bond, and R is a hydrogen atom, a halogen atom, a C cycloalkyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl 40 group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ). 3a 2a Another more preferred embodiment of the substituent L and the substituent R 3a 2a is such that L is a single bond, and R is a 3 to 11-membered non-aromatic heterocyclyl group (the 3 to 11-membered non-aromatic heterocyclyl group is unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ). 3a 2a Another more preferred embodiment of the substituent L and the substituent R 3a 2a is such that L is a single bond, and R is a C cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are substituted with identical or different one ,two or three substituents independently selected from the group consisting of C alkyl groups, C alkoxy 1-6 1-6 groups, C alkylthio groups, C alkylsulfonyl groups, C alkylcarbonyl groups (the C 1-6 1-6 1-6 1- alkyl groups, the C alkoxy groups, the C alkylthio groups, the C alkylsulfonyl 6 1-6 1-6 1-6 groups and the C alkylcarbonyl groups are substituted with a substituent selected from the group consisting of a hydroxy group, a cyano group, a C alkoxy group and a C alkoxycarbonylamino group), C alkoxycarbonyl groups, mono-C alkylamino 1-6 1-6 1-6 groups, di-C alkylamino groups, mono-C alkylaminocarbonyl groups, di-C 1-6 1-6 1-6 alkylaminocarbonyl groups, C alkylcarbonylamino groups, (the C alkoxycarbonyl 1-6 1-6 groups, the mono-C alkylamino groups, the di-C alkylamino groups, the mono-C 1-6 1-6 1-6 alkylaminocarbonyl groups, the di-C alkylaminocarbonyl groups and the C 1-6 1-6 alkylcarbonylamino groups are substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms or with a hydroxy group or a cyano group), mono-alkylaminosulfonyl groups, di-C alkylaminosulfonyl groups, C 1-6 1-6 alkylsulfonylamino groups, C alkoxycarbonylamino groups (the mono-C 1-6 1-6 alkylaminosulfonyl groups, the di-C alkylaminosulfonyl groups, the C 1-6 1-6 alkylsulfonylamino groups and the C alkoxycarbonylamino groups are unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms), phenyl groups and 5 to 6-membered aromatic heterocyclyl groups (the phenyl groups and the 5 to 6-membered aromatic heterocyclyl groups are unsubstituted or substituted with one or two identical or different substituents independently selected from the substituent set V )). 3a 2a Another more preferred embodiment of the substituent L and the substituent R 3a 2a is such that L is a single bond, and R is a C cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11-membered non-aromatic 40 heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are substituted with a substituent selected from the group consisting of a C alkyl group, a C alkoxy group (the C alkyl group and the C alkoxy group are 1-6 1-6 1-6 substituted with a hydroxy group or a cyano group), a mono-C alkylamino group, a di- C alkylamino group, a mono-C alkylaminocarbonyl group, a C alkylcarbonylamino 1-6 1-6 1-6 45 group (the mono-C alkylamino group, the di-C alkylamino group, the mono-C 1-6 1-6 1-6 alkylaminocarbonyl group and the C alkylcarbonylamino group are substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups and cyano groups), a phenyl group, a 5 to 6-membered aromatic heterocyclyl group (the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms, cyano groups, C alkyl groups and C haloalkyl groups), a mono-C 1-6 1-6 1-6 alkylaminosulfonyl group, a di-C alkylaminosulfonyl group, a C alkylsulfonylamino 1-6 1-6 group and a C alkoxycarbonylamino group (the mono-C alkylaminosulfonyl group, 1-6 1-6 the di-C alkylaminosulfonyl group, the C alkylsulfonylamino group and the C 1-6 1-6 1-6 alkoxycarbonylamino group are unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms) and with one or more identical or different substituents independently selected from the group consisting of hydroxy groups, halogen atoms, cyano groups, C alkyl groups, C haloalkyl groups, C 1-6 1-6 1-6 alkoxy groups, C haloalkoxy groups, C alkylsulfonyl groups and C 1-6 1-6 1-6 haloalkylsulfonyl groups). 3a 2a Another more preferred embodiment of the substituent L and the substituent R 3a 2a is such that L is a single bond, and R is an azido group. 3a 2a Another more preferred embodiment of the substituent L and the substituent R 3a 2a is such that L is a single bond, and R is a 8 to 11-membered partially saturated aromatic cyclic group (the 8 to 11-membered partially saturated aromatic cyclic group is unsubstituted or substituted with one or two identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms). 3a 2a Another more preferred embodiment of the substituent L and the substituent R 3a a a is such that L is represented by any of the following formulae (IX -1) to (IX -9): S S N O O a O 12 a a a a a (IX -5) (IX -1) ( IX -2) ( IX -3) (IX -4) (IX ) a a a a (IX -6) (IX -7) (IX -8) (IX -9) 12a 2a (wherein R is a hydrogen atom or a C alkyl group), and R is a hydrogen atom, a C alkyl group or a C haloalkyl group (the C alkyl group and the C haloalkyl 1-6 1-6 1-6 1-6 group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, amino groups, carbamoyl groups, sulfamoyl groups, tetrazolyl groups, cyano groups, nitro groups, C cycloalkyl groups, C alkoxy groups, C haloalkoxy groups, C alkylsulfonyl groups, 1-3 1-6 1-3 C haloalkylsulfonyl groups, 4 to 7-membered non-aromatic heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups). 3a 2a Another more preferred embodiment of the substituent L and the substituent R 3a a a is such that L is represented by any of the following formulae (IX -1) to (IX -9): O O a O 12 a a a a (IX -5) (IX -1) ( IX -2) ( IX -3) (IX -4) (IX ) (IX -6) (IX -7) (IX -8) (IX -9) 12a 2a (wherein R is a hydrogen atom, a C alkyl group or a C haloalkyl group), and R 1-3 1-3 is a hydrogen atom, a C alkyl group, a C haloalkyl group (the C alkyl group and 1-6 1-6 1-6 the C haloalkyl group are unsubstituted or substituted with one, two or three identical or different substituents independently selected from the group consisting of hydroxy groups, amino groups, carbamoyl groups, sulfamoyl groups, cyano groups, nitro groups, C alkoxy groups, C haloalkoxy groups, C alkylsulfonyl groups, C 1-6 1-6 1-6 1-6 haloalkylsulfonyl groups, mono-C alkylamino groups, di-C alkylamino groups, 1-6 1-6 mono-C alkylaminocarbonyl groups, di-C alkylaminocarbonyl groups (the mono-C 1-6 1-6 1-6 alkylamino groups, the di-C alkylamino groups, the mono-C alkylaminocarbonyl 1-6 1-6 groups and the di-C alkylaminocarbonyl groups are unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms), C cycloalkyl groups, 3 to 11-membered non-aromatic heterocyclyl groups, phenyl groups and 5 to 10-membered aromatic heterocyclyl groups (the C cycloalkyl groups, the 3 to 11-membered non-aromatic heterocyclyl groups, the phenyl groups and the 5 to 10- membered aromatic heterocyclyl groups are unsubstituted or substituted with identical or different one or more substituents independently selected from the group consisting of hydroxy groups, amino groups, halogen atoms, cyano groups, carbamoyl groups, C alkoxy groups, C haloalkoxy groups, C alkylthio groups, C haloalkylthio groups, 1-6 1-6 1-6 C alkylsulfonyl groups, C haloalkylsulfonyl groups, mono-C alkylamino groups, di- 1-6 1-6 1-6 C alkylamino groups, mono-C alkylaminocarbonyl groups, di-C 1-6 1-6 1-6 alkylaminocarbonyl groups, C alkylcarbonylamino groups,C alkoxycarbonyl groups 1-6 1-6 (the mono-C alkylamino groups, the di-C alkylamino groups, the mono-C 1-6 1-6 1-6 alkylaminocarbonyl groups, the di-C alkylaminocarbonyl groups, the C 1-6 1-6 alkylcarbonylamino groups and the C alkoxycarbonyl groups are unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms), 4 to 7-membered non-aromatic heterocyclyl groups, phenyl groups and 5 to 6- membered aromatic heterocyclyl groups)), a C cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 10-membered aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 10-membered aromatic heterocyclyl group are unsubstituted or substituted with identical or different one or more substituents independently selected from the group consisting of hydroxy groups, amino groups, halogen atoms, cyano groups, carbamoyl groups, C alkyl groups (the C 1-6 1-6 alkyl groups are unsubstituted or substituted with a substituent selected from the group consisting of a hydroxy group, a cyano group and a C alkoxy group), C haloalkyl 1-3 1-6 groups, C alkoxy groups, C haloalkoxy groups, C alkylthio groups, C 1-6 1-6 1-6 1-6 haloalkylthio groups, C alkylsulfonyl groups, C haloalkylsulfonyl groups, mono-C 1-6 1-6 1-6 alkylamino groups, di-C alkylamino groups, mono-C alkylaminocarbonyl groups, di- 1-6 1-6 C alkylaminocarbonyl groups, C alkylcarbonylamino groups, C alkoxycarbonyl 1-6 1-6 1-6 groups (the mono-C alkylamino groups, the di-C alkylamino groups, the mono-C 1-6 1-6 1-6 alkylaminocarbonyl groups, the di-C alkylaminocarbonyl groups, the C 1-6 1-6 alkylcarbonylamino groups and the C alkoxycarbonyl groups are unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms), 4 to 7-membered non-aromatic heterocyclyl groups, phenyl groups and 5 to 6- membered aromatic heterocyclyl groups (the phenyl groups and the 5 to 6-membered aromatic heterocyclyl groups are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms, cyano groups and C haloalkyl groups)). 3a 2a Another more preferred embodiment of the substituent L and the substituent R 3a a a is such that L is represented by any of the following formulae (XVII -1) to (XVII -3): ,and R is a hydrogen atom or a C alkyl group. 3a 2a Another more preferred embodiment of the substituent L and the substituent R 3a a is such that L is represented by the formula (XVIII ): 12a 2a (wherein R is a hydrogen atom), and R is a C alkyl group (the C alkyl group is, 1-6 1-6 unsubstituted or substituted with a phenyl group). 3a 2a Another more preferred embodiment of the substituent L and the substituent R 3a a a is such that L is represented by any of the following formulae (IX -1) to (IX -9): S S N O O a O 12 a a a a (IX -5) (IX -1) ( IX -2) ( IX -3) (IX -4) (IX ) (IX -6) (IX -7) (IX -8) (IX -9) 12a 2a (wherein R is a hydrogen atom, a C alkyl group or a C haloalkyl group), and R 1-3 1-3 is a C alkyl group, a C haloalkyl group (the C alkyl group and the C haloalkyl 1-6 1-6 1-6 1-6 group are substituted with a substituent selected from the group consisting of a C cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a phenyl group and a 5 to 10-membered aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 10- membered aromatic heterocyclyl group are substituted with one or two identical or different substituents independently selected from the group consisting of C alkyl groups (the C alkyl groups are unsubstituted or substituted with a hydroxy group or a cyano group) and C haloalkyl groups)) or a C alkynyl group. 1-6 2-6 3a 2a Another more preferred embodiment of the substituent L and the substituent R 3a a a is such that L is represented by any of the following formulae (IX -1) to (IX -9): S S N O O a O 12 a a a a a (IX -5) (IX -1) ( IX -2) ( IX -3) (IX -4) (IX ) a a a a (IX -6) (IX -7) (IX -8) (IX -9) 12a 2a (wherein R is a hydrogen atom, a C alkyl group or a C haloalkyl group), and R 1-3 1-3 is a C alkyl group or a C haloalkyl group (the C alkyl group and the C haloalkyl 1-6 1-6 1-6 1-6 group are substituted with a substituent selected from the group consisting of a C cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a phenyl group and a 5 to 10-membered aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 10- membered aromatic heterocyclyl group are substituted with one or two identical or different substituents independently selected from the group consisting of C alkyl groups and C haloalkyl groups and with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, amino groups, halogen atoms, cyano groups, C alkoxy groups, C haloalkoxy groups, mono-C 1-6 1-6 1-6 alkylamino groups, di-C alkylamino groups, C alkylthio groups, C haloalkylthio 1-6 1-6 1-6 groups, C alkylsulfonyl groups, C haloalkylsulfonyl groups, C cycloalkyl groups, 4 1-6 1-6 3-6 to 7-membered non-aromatic heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups)). 3a 2a Another more preferred embodiment of the substituent L and the substituent R 3a a is such that L is represented by the formula (XVI ): (XVI ) 12a 2a (wherein R is a hydrogen atom), and R is a 8 to 11-membered partially saturated aromatic cyclic group or a 8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon group (the 8 to 11-membered partially saturated aromatic cyclic group and the 8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms and hydroxy groups). 3a 2a Another more preferred embodiment of the substituent L and the substituent R 3a a is such that L is represented by the formula (X -10): (X -10) 1a 11a 11a 2a (wherein E is NR (wherein R is a hydroxy group)), and R is a hydrogen atom. 3a 2a Another more preferred embodiment of the substituent L and the substituent R 3a a a is such that L is represented by any of the following formulae (XXVI -1) to (XXVI -5): 1a 12a (wherein E is an oxygen atom, and R is a C alkyl group (the C alkyl group is 1-6 1-6 substituted with a substituent selected from the group consisting of a hydroxy group, a cyano group, a C alkoxy group, a C cycloalkyl group, a 4 to 7-membered non- 1-3 3-6 aromatic heterocyclyl group, a phenyl group and a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with a substituent selected from the group consisting of a hydroxy group, a halogen atom, a cyano group, a C alkyl group, a C 1-3 1-3 haloalkyl group and a C alkoxy group)), a C cycloalkyl group, a 4 to 7-membered 1-3 3-6 non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, halogen atoms, cyano groups, C alkyl groups, C haloalkyl groups and C alkoxy groups)), and 1-3 1-3 1-3 R is a C alkyl group, a C haloalkyl group (the C alkyl group and the C 1-6 1-6 1-6 1-6 haloalkyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, cyano groups, C alkoxy groups, mono-C alkylaminocarbonyl groups, (the mono-C 1-3 1-6 1-6 alkylaminocarbonyl groups are unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms), C cycloalkyl groups, 4 to 7- membered non-aromatic heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups (the C cycloalkyl groups, the 4 to 7-membered non- aromatic heterocyclyl groups, the phenyl groups and the 5 to 6-membered aromatic heterocyclyl groups are unsubstituted or substituted with identical or different one or two substituents independently selected from the group consisting of hydroxy groups, halogen atoms, cyano groups, carbamoyl groups, C alkyl groups, C haloalkyl 1-6 1-6 groups, C alkoxy groups, C haloalkoxy groups, mono-C alkylamino groups and 1-6 1-6 1-6 di-C alkylamino groups)), a C alkynyl group, a C cycloalkyl group, a 4 to 7- 1-6 2-6 3-6 membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non- aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one, two or three identical or different substituents independently selected from the group consisting of hydroxy groups, halogen atoms, cyano groups, carbamoyl groups, C alkyl groups, C 1-6 1-6 haloalkyl groups, C alkoxy groups, C halo alkoxy groups, mono-C alkylamino 1-6 1-6 1-6 groups, di-C alkylamino groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl group). 3a 2a A further preferred embodiment of the substituent L and the substituent R is 3a 2a such that L is a single bond, and R is a hydrogen atom, a halogen atom, a C cycloalkyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with identical or different one, two or thee substituents independently selected from the group consisting of hydroxy groups, amino groups, halogen atoms, cyano groups, nitro groups, carbamoyl groups, sulfamoyl groups, C alkyl groups, C haloalkyl groups, C alkoxy groups, C haloalkoxy 1-6 1-6 1-6 1-6 groups, mono-C alkylamino groups, di-C alkylamino groups, C alkylthio groups, 1-6 1-6 1-6 C haloalkylthio groups, C alkylcarbonyl groups, C haloalkylcarbonyl groups, C 1-6 1-6 1-6 1-6 alkylsulfonyl groups, C haloalkylsulfonyl groups, carboxy groups, C alkoxycarbonyl 1-6 1-6 groups, mono-C alkylaminocarbonyl groups, di-C alkylaminocarbonyl groups, C 1-6 1-6 1-6 alkylcarbonylamino groups, C cycloalkyl groups and 4 to 7-membered non-aromatic 40 heterocyclyl groups).

Another further preferred embodiment of the substituent L and the substituent 2a 3a 2a R is such that L is a single bond, and R is a 3 to 11-membered non-aromatic heterocyclyl group (the 3 to 11-membered non-aromatic heterocyclyl group is unsubstituted or substituted with one, two or three identical or different substituents 45 independently selected from the group consisting of hydroxy groups, amino groups, halogen atoms, cyano groups, nitro groups, carbamoyl groups, sulfamoyl groups, C alkyl groups, C haloalkyl groups, C alkoxy groups, C haloalkoxy groups, mono- 1-6 1-6 1-6 C alkylamino groups, di-C alkylamino groups, C alkylthio groups, C 1-6 1-6 1-6 1-6 haloalkylthio groups, C alkylcarbonyl groups, C haloalkylcarbonyl groups, C 1-6 1-6 1-6 alkylsulfonyl groups, C haloalkylsulfonyl groups, carboxy groups, C alkoxycarbonyl 1-6 1-6 groups, mono-C alkylaminocarbonyl groups, di-C alkylaminocarbonyl groups, C 1-6 1-6 1-6 alkylcarbonylamino groups, C cycloalkyl groups and 4 to 7-membered non-aromatic heterocyclyl groups).

Another further preferred embodiment of the substituent L and the substituent 2a 3a 2a R is such that L is a single bond, and R is a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 6- membered aromatic heterocyclyl group are substituted with a C alkyl group, a C 1-6 1-6 alkoxy group (the C alkyl group and the C alkoxy group are substituted with a 1-6 1-6 substituent selected from the group consisting of a hydroxy group, a cyano group and a C alkoxycarbonylamino group), a mono-C alkylamino group, a di-C alkylamino 1-6 1-6 1-6 group, a mono-C alkylaminocarbonyl group, a C alkylcarbonylamino group (the 1-6 1-6 mono-C alkylamino group, the di-C alkylamino group, the mono-C 1-6 1-6 1-6 alkylaminocarbonyl group and the C alkylcarbonylamino group are substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms or with a hydroxy group or a cyano group), a C alkoxycarbonyamino group, a phenyl group and a 5 to 6-membered aromatic heterocyclyl group (the phenyl group and the 5 to 6- membered aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms, cyano groups, C alkyl groups and C haloalkyl groups)). 1-3 1-3 Another further preferred embodiment of the substituent L and the substituent 2a 3a 2a R is such that L is a single bond, R is a 3 to 11-membered non-aromatic heterocyclyl group (the 3 to 11-membered non-aromatic heterocyclyl group is substituted with a di-C alkylaminosulfonyl group).

Another further preferred embodiment of the substituent L and the substituent 2a 3a 2a R is such that L is a single bond, R is a 4 to 7-membered non-aromatic heterocyclyl group (the 4 to 7-membered non-aromatic heterocyclyl group is substituted with a phenyl group (the phenyl group is unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms, C alkyl groups and C haloalkyl groups) and with a substituent 1-3 1-3 selected from the group consisting of a hydroxy group, a halogen atom, a cyano group, a C alkyl group and a C haloalkyl group). 1-3 1-3 Another further preferred embodiment of the substituent L and the substituent 2a 3a a a R is such that L is represented by any of the following formulae (XX -1) to (XX -3): 12a 2a 40 (wherein R is a hydrogen atom or a C alkyl group), and R is a hydrogen atom, a C alkyl group or a C haloalkyl group (the C alkyl group and the C haloalkyl 1-6 1-6 1-6 1-6 group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, cyano groups, C alkoxy groups, C cycloalkyl groups, 4 to 7-membered non-aromatic heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups).

Another further preferred embodiment of the substituent L and the substituent 2a 3a a a R is such that L is represented by any of the following formulae (XXI -1) to (XXI -3): and R is a hydrogen atom or a C alkyl group (the C alkyl group is unsubstituted or 1-6 1-6 substituted with a phenyl groups).

Another further preferred embodiment of the substituent L and the substituent 2a 3a a R is such that L is represented by the formula (X -4): S (X -4) , and R is a C haloalkyl group.

Another further preferred embodiment of the substituent L and the substituent 2a 3a a R is such that L is represented by any of the following formulae (XXVIII -1) to (XXVIII -3): (XXVIII ) R O O a a a (XXVIII -1) (XXVIII -2) (XXVIII -3) 1a 12a (wherein E is an oxygen atom, and R is a hydrogen atom or a C alkyl group), and R is a C alkyl group (the C alkyl group is unsubstituted or substituted with a cyano 1-6 1-6 group) or a C haloalkyl group.

Another further preferred embodiment of the substituent L and the substituent 2a 3a a a R is such that L is represented by any of the following formulae (XX -1) to (XX -3): 12a 2a (wherein R is a hydrogen atom or a C alkyl group), and R is a C alkyl group or 1-3 1-6 a C haloalkyl group (the C alkyl group and the C haloalkyl group are substituted 1-6 1-6 1-6 with a substituent selected from the group consisting of a mono-C alkylaminocarbonyl group (the mono-C alkylaminocarbonyl group is unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms), a C cycloalkyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group and a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 6- membered aromatic heterocyclyl group are substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, amino groups, halogen atoms, cyano groups, carbamoyl groups, C alkoxy groups, C haloalkoxy groups, mono-C alkylamino groups, di-C alkylamino groups, 1-6 1-6 1-6 C alkylthio groups, C haloalkylthio groups, C alkylsulfonyl groups, C 1-6 1-6 1-6 1-6 haloalkylsulfonyl groups, C alkoxycarbonyl groups and phenyl groups (the phenyl groups are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms and C haloalkyl groups))).

Another further preferred embodiment of the substituent L and the substituent 2a 3a a a R is such that L is represented by any of the following formulae (XX -1) to (XX -3): 12a 2a (wherein R is a hydrogen atom or a C alkyl group), and R is a C alkyl group or 1-3 1-6 a C haloalkyl group (the C alkyl group and the C haloalkyl group are substituted 1-6 1-6 1-6 with a substituent selected from the group consisting of a C cycloalkyl group, a 4 to 7- membered non-aromatic heterocyclyl group, a phenyl group and a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non- aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, amino groups, halogen atoms, cyano groups, carbamoyl groups, C alkoxy groups, C haloalkoxy 1-6 1-6 groups, mono-C alkylamino groups, di-C alkylamino groups, C alkylthio groups, 1-6 1-6 1-6 C haloalkylthio groups, C alkylsulfonyl groups, C haloalkylsulfonyl groups and 4 1-6 1-6 1-6 to 7-membered non-aromatic heterocyclyl groups) and with a substituent selected from the group consisting of a hydroxy group and a cyano group).

Another further preferred embodiment of the substituent L and the substituent 2a 3a a R is such that L is represented by any of the following formulae (XXVII -1) to (XXVII -5): 12a 2a (wherein R is a hydrogen atom or a C alkyl group), and R is a C cycloalkyl 1-3 3-6 group, a 3 to 11-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to -membered aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11- membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 10- membered aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, amino groups, halogen atoms, cyano groups, carbamoyl groups, C alkyl groups (the C alkyl groups are unsubstituted or substituted with a substituent selected from the group consisting of a hydroxy group, a cyano group and a C alkoxy group), C haloalkyl groups, C alkoxy groups, C haloalkoxy groups, mono-C 1-6 1-6 1-6 1-6 alkylamino groups, di-C alkylamino groups, C alkylthio groups, C haloalkylthio 1-6 1-6 1-6 groups, C alkylsulfonyl groups, C haloalkylsulfonyl groups, C alkoxycarbonyl 1-6 1-6 1-6 groups, 4 to 7-membered non-aromatic heterocyclyl groups, phenyl groups and 5 to 6- membered aromatic heterocyclyl groups (the phenyl groups and the 5 to 6-membered aromatic heterocyclyl groups are unsubstituted or substituted with a halogen atom)).

Another further preferred embodiment of the substituent L and the substituent 2a 3a a a R is such that L is represented by any of the following formulae (XXVI -1) to (XXVI - 1a 12a 2a (wherein E is an oxygen atom, and R is a C haloalkyl group), and R is a C 1-6 1-6 alkyl group (the C alkyl group is unsubstituted or substituted with a substituent selected from the group consisting of a hydroxy group, a cyano group, a C alkoxy group, a C cycloalkyl group and a phenyl group) or a C haloalkyl group. 3-6 1-6 Another further preferred embodiment of the substituent L and the substituent 2a 3a a R is such that L is represented by the formula (X -5): (X -5) , and R is a C alkyl group.

Another further preferred embodiment of the substituent L and the substituent 2a 3a a R is such that L is represented by the formula (X -6): (X -6) , and R is a hydrogen atom.

Another further preferred embodiment of the substituent L and the substituent 2a 3a a R is such that L is represented by the formula (XVIII ): (XVIII ) 12a 2a (wherein R is a hydrogen atom), and R is a C alkyl group or a C alkyl group 1-6 1-3 (the C alkyl group is substituted with a phenyl group).

Another further preferred embodiment of the substituent L and the substituent 2a 3a a R is such that L is represented by the formula (X -8): , and R is a C alkyl group.

Another further preferred embodiment of the substituent L and the substituent 2a 3a a a R is such that L is represented by any of the following formulae (XX -1) to (XX -3): 12a 2a (wherein R is a hydrogen atom or a C alkyl group), and R is a C alkyl group 1-3 1-3 (the C alkyl group is substituted with a substituent selected from the group consisting of a C cycloalkyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group and a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 6- membered aromatic heterocyclyl group are substituted with a C alkyl group or a C 1-3 1-3 haloalkyl group)) or a C alkynyl group.

Another further preferred embodiment of the substituent L and the substituent 2a 3a a a R is such that L is represented by any of the following formulae (XX -1) to (XX -3): 12a 2a (wherein R is a hydrogen atom or a C alkyl group), and R is a C alkyl group 1-3 1-3 (the C alkyl group is substituted with a substituent selected from the group consisting of a phenyl group and a 5 to 6-membered aromatic heterocyclyl group (the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are substituted with a C alkyl group or a C haloalkyl group and with a substituent selected from the group consisting of a halogen atom, a cyano group, a C alkoxy group, a C haloalkoxy 1-3 1-3 group and a C alkylsulfonyl group)).

Another further preferred embodiment of the substituent L and the substituent 2a 3a a R is such that L is represented by the formula (XVI ): ( XVI ) 12a 2a (wherein R is a hydrogen atom), and R is a 8 to 11-membered partially saturated aromatic cyclic group or a 8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon group (the 8 to 11-membered partially saturated aromatic cyclic group and the 8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms and hydroxy groups).

Another further preferred embodiment of the substituent L and the substituent 2a 3a a a R is such that L is represented by any of the following formulae (XXVI -1) to (XXVI - 1a 12a (wherein E is an oxygen atom, and R is a C alkyl group (the C alkyl group is 1-3 1-3 substituted with a substituent selected from the group consisting of a cyano group, a hydroxy group, a C alkoxy group, a C cycloalkyl group, a phenyl group and a 5 to 6- 1-3 3-6 membered aromatic heterocyclyl group (the 5 to 6-membered aromatic heterocyclyl group is unsubstituted or substituted with a C alkyl group)), a C cycloalkyl group or 1-3 3-6 a phenyl group (the phenyl group is unsubstituted or substituted with a halogen or a cyano group)), and R is a C alkyl group, a C haloalkyl group (the C alkyl group and the C 1-3 1-3 1-3 1-3 haloalkyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, cyano groups, C alkoxy groups, C cycloalkyl groups, phenyl groups and 5 to 6-membered 1-3 3-6 aromatic heterocyclyl groups). 3a 2a A particularly preferred embodiment of the substituent L and the substituent R 3a 2a is such that L is a single bond, and R is a hydrogen atom or a halogen atom.

Another particularly preferred embodiment of the substituent L and the 2a 3a 2a substituent R is such that L is a single bond, and R is a C cycloalkyl group (the C cycloalkyl group is unsubstituted or substituted with a C haloalkyl group). 3-6 1-3 Another particularly preferred embodiment of the substituent L and the 2a 3a 2a substituent R is such that L is a single bond, and R is a phenyl group or a 5 to 6- membered aromatic heterocyclyl group (the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one, two or three identical or different substituents independently selected from the group consisting of halogen atoms, cyano groups, carbamoyl groups, C alkyl groups, C alkoxy groups, 1-3 1-3 C alkylthio groups, C alkylsulfonyl groups, C haloalkyl groups, C haloalkoxy 1-3 1-3 1-3 1-3 groups, C haloalkylthio groups and 4 to 7-membered non-aromatic heterocyclyl groups).

Another particularly preferred embodiment of the substituent L and the 2a 3a 2a substituent R is such that L is a single bond, and R is a 4 to 7-membered non- aromatic heterocyclyl group (the 4 to 7-membered non-aromatic heterocyclyl group is unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of cyano groups, halogen atoms, C alkyl groups, C haloalkyl groups, hydroxy groups, di-C alkylamino groups, carboxy 1-3 1-3 groups, carbamoyl groups, C haloalkoxy groups, C alkylcarbonylamino groups and 1-3 1-3 4 to 7-membered non-aromatic heterocyclyl groups).

Another particularly preferred embodiment of the substituent L and the 2a 3a 2a substituent R is such that L is a single bond, and R is a phenyl group (the phenyl group is substituted with a substituent selected from the group consisting of a C alkoxy group, a di-C alkylamino group (the C alkoxy group and the di-C 1-3 1-3 1-3 40 alkylamino group are substituted with a hydroxy group or a cyano group) and a 5 to 6- membered aromatic heterocyclyl group).

Another particularly preferred embodiment of the substituent L and the 2a 3a 2a substituent R is such that L is a single bond, and R is a 5 to 6-membered aromatic heterocyclyl group (the 5 to 6-membered aromatic heterocyclyl group is substituted with a C alkyl group (the C alkyl group is substituted with a hydroxy group). 1-3 1-3 Another particularly preferred embodiment of the substituent L and the 2a 3a 2a substituent R is such that L is a single bond, and R is a 4 to 7-membered non- aromatic heterocyclyl group (the 4 to 7-membered non-aromatic heterocyclyl group is substituted with a substituent selected from the group consisting of a C alkyl group (the C alkyl group is substituted with a substituent selected from the group consisting of a hydroxy group, a cyano group and a C alkoxycarbonylamino group), a mono-C 1-6 1-3 alkylaminocarbonyl group, a C alkylcarbonylamino group (the mono-C 1-3 1-3 alkylaminocarbonyl group and the C alkylcarbonylamino group are substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms) and a C alkoxycarbonylamino group).

Another particularly preferred embodiment of the substituent L and the 2a 3a 2a substituent R is such that L is a single bond, and R is a 4 to 7-membered non- aromatic heterocyclyl group (the 4 to 7-membered non-aromatic heterocyclyl group is substituted with a phenyl group (the phenyl group is unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms and C haloalkyl groups) and with a hydroxy group or a cyano group).

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (X -1): (X -1) , and R is a methyl group (the methyl group is unsubstituted or substituted with a cyano group).

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (X -1): (X -1) , and R is a hydrogen atom or a C haloalkyl group.

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (X -1): (X -1) ,and R is a 4 to 7-membered non-aromatic heterocyclyl group or a phenyl group (the 4 to 7- membered non-aromatic heterocyclyl group and the phenyl group are unsubstituted or substituted with a substituent selected from the group consisting of a hydroxy group, a cyano group, a halogen atom and a C haloalkyl group).

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (X -7): ( X -7) 12a 2a (wherein R is a hydrogen atom), and R is a hydrogen atom, a C alkyl group or a C haloalkyl group (the C alkyl group and the a C haloalkyl group are 1-3 1-3 1-3 unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, cyano groups and phenyl groups).

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (X -7): ( X -7) 12a 2a (wherein R is a hydrogen atom), and R is a C alkyl group (the C alkyl group is 1-3 1-3 substituted with a phenyl group (the phenyl group is substituted with a halogen atom or a cyano group)).

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (X -7): ( X -7) 12a 2a (wherein R is a hydrogen atom), and R is a C haloalkyl group (the C haloalkyl 1-3 1-3 group is substituted with a phenyl group (the phenyl group is substituted with a halogen atom) and with a hydroxy group).

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (X -7): ( X -7) 12a 2a (wherein R is a hydrogen atom), and R is a C cycloalkyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with a substituent selected from the group consisting of a C alkyl group, a C haloalkyl group and a halogen atom).

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (XVI ): (XVI ) 12a 2a (wherein R is a hydrogen atom or a C alkyl group), and R is a hydrogen atom, a C alkyl group (the C alkyl group is unsubstituted or substituted with a substituent 1-6 1-6 selected from the group consisting of a hydroxy group, a cyano group, a C alkoxy group, a C cycloalkyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group and a 5 to 6-membered aromatic heterocyclyl group) or a C haloalkyl group (the C haloalkyl group is unsubstituted or substituted with a hydroxy group).

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (XVI ): (XVI ) 12a 2a (wherein R is a C haloalkyl group), and R is a C alkyl group (the C alkyl 1-3 1-3 1-3 group is substituted with a C cycloalkyl group).

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (XVI ): (XVI ) 12a 2a (wherein R is a hydrogen atom), and R is a C alkyl group or a C haloalkyl group 1-3 1-3 (the C alkyl group and the C haloalkyl group are substituted with a hydroxy group 1-3 1-3 and with a phenyl group or a 5 to 6-membered aromatic heterocyclyl group).

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (XVI ): (XVI ) 12a 2a (wherein R is a hydrogen atom or a C alkyl group), and R is a C alkyl group 1-3 1-6 (the C alkyl group is substituted with a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms, cyano groups, C alkoxy groups, C haloalkoxy groups and C alkylsulfonyl groups)). 1-3 1-3 Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (XVI ): (XVI ) 12a 2a (wherein R is a hydrogen atom), and R is a C alkyl group (the C alkyl group is 1-6 1-6 substituted with a C cycloalkyl group or a 4 to 7-membered non-aromatic heterocyclyl group (the C cycloalkyl group and the 4 to 7-membered non-aromatic heterocyclyl group are substituted with a substituent selected from the group consisting of a hydroxy group, a C alkoxycarbonyl group and a phenyl group (the phenyl group is unsubstituted or substituted with a halogen atom))).

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (XVI ): (XVI ) 12a 2a (wherein R is a hydrogen atom), and R is a C alkyl group or a C haloalkyl group 1-3 1-3 (the C alkyl group and the C haloalkyl group are substituted with a phenyl group or 1-3 1-3 a 5 to 6-membered aromatic heterocyclyl group (the phenyl group and the 5 to 6- membered aromatic heterocyclyl group are substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms, C alkoxy groups, C haloalkoxy groups and C alkylthio groups) and with a 1-3 1-3 1-3 hydroxy group).

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (XVI ): (XVI ) 12a 2a (wherein R is a hydrogen atom or a C alkyl group), and R is a C cycloalkyl 1-3 3-6 group, a 4 to 7-membered non-aromatic heterocyclyl group (the C cycloalkyl group and the 4 to 7-membered non-aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, C alkyl groups (the C alkyl groups are 1-3 1-3 unsubstituted or substituted with a substituent selected from the group consisting of a hydroxy group, a cyano group and a C alkoxy group), C haloalkyl groups, C 1-3 1-3 1-6 alkoxycarbonyl groups and phenyl groups (the phenyl groups are unsubstituted or substituted with a halogen atom)), a phenyl group or a 5 to 10-membered aromatic heterocyclyl group (the phenyl group and the 5 to 10-membered aromatic heterocyclyl group are unsubstituted or substituted with identical or different one, two or three substituents independently selected from the group consisting of halogen atoms, cyano groups, C alkyl groups, C haloalkyl groups, C alkoxy groups, C haloalkoxy 1-3 1-3 1-3 1-3 groups, C haloalkylsulfonyl groups and 4 to 7-membered non-aromatic heterocyclyl groups).

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (X -2): ( X -2) , and R is a methyl group (the methyl group is unsubstituted or substituted with a phenyl group).

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (X -2): ( X -2) , and R is a hydrogen atom or a t-butyl group.

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (X -3): ( X -3) , and R is a hydrogen atom.

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (X -3): ( X -3) , and R is a C alkyl group.

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (X -4): (X -4) , and R is a C alkyl group.

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (X -4): (X -4) , and R is a C cycloalkyl group or a phenyl group (the phenyl group is unsubstituted or substituted with a halogen atom).

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (X -11): (X -11) 12a 2a (wherein R is a hydrogen atom or a C alkyl group), and R is a C alkyl group 1-3 1-3 (the C alkyl group is unsubstituted or substituted with a cyano group) or a C 1-3 1-3 haloalkyl group.

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (X -11): (X -11) 12a 2a (wherein R is a C haloalkyl group), and R is a C alkyl group (the C alkyl 1-3 1-3 1-3 group is unsubstituted or substituted with a cyano group) or a C haloalkyl group.

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (X -12): ( X -12 ) 12a 2a (wherein R is a hydrogen atom or a C alkyl group), and R is a C alkyl group 1-3 1-3 (the C alkyl group is unsubstituted or substituted with a cyano group) or a C 1-3 1-3 haloalkyl group.

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (X -12): ( X -12 ) 12a 2a (wherein R is a hydrogen atom), and R is a C cycloalkyl group.

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (X -13): 12a 2a (wherein R is a hydrogen atom), and R is a C alkyl group.

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (X -5): ( X -5) , and R is a methyl group.

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (XVIII ): (XVIII ) 12a 2a (wherein R is a hydrogen atom), and R is a methyl group (the methyl group is substituted with a phenyl group) or a t-butyl group.

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (X -8): , and R is a methyl group.

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (X -7): ( X -7) 12a 2a (wherein R is a hydrogen atom), and R is a C alkyl group (the C alkyl group is 1-3 1-3 substituted with a 5 to 6-membered aromatic heterocyclyl group (the 5 to 6-membered aromatic heterocyclyl group is substituted with a C alkyl group)).

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (XVI ): ( XVI ) 12a 2a (wherein R is a hydrogen atom), and R is a C alkyl group (the C alkyl group is 1-3 1-3 substituted with a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are substituted with a C alkyl group or a C haloalkyl group)) or a C alkynyl group. 1-3 1-3 2-6 Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (XVI ): ( XVI ) 12a 2a (wherein R is a hydrogen atom), and R is a C alkyl group (the C alkyl group is 1-3 1-3 substituted with a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are substituted with a C alkyl group or a C haloalkyl group and with a halogen atom)). 1-3 1-3 Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (X -11): (X -11) (wherein R is a C alkyl group (the C alkyl group is substituted with a cyano group 1-3 1-3 or a 5 to 6-membered aromatic heterocyclyl group (the 5 to 6-membered aromatic heterocyclyl group is unsubstituted or substituted with a C alkyl group)) or a C 1-3 3-6 cycloalkyl group), and R is a C alkyl group (the C alkyl group is unsubstituted or 1-3 1-3 substituted with a cyano group) or a C haloalkyl group.

Another particularly preferred embodiment of the substituent L and the 2a 3a a substituent R is such that L is represented by the formula (XVI ): ( XVI ) (wherein R is a C alkyl group (the C alkyl group is substituted with a substituent 1-3 1-3 selected from the group consisting of a cyano group, a hydroxy group, a C alkoxy group, a C cycloalkyl group and a phenyl group), a C cycloalkyl group or a phenyl 3-6 3-6 group), and R is a C alkyl group (the C alkyl group is substituted with a substituent 1-3 1-3 selected from the group consisting of a cyano group, a hydroxy group, a C alkoxy group, a C cycloalkyl group and a phenyl group). a 3a a A preferred embodiment of n and the substituent R is such that n is 0, 1 or 2, and R is a hydroxy group, an amino group, a halogen atom, a cyano group, a C alkyl group, a C haloalkyl group, a C alkoxy group or a C haloalkoxy group (when 1-3 1-3 1-3 a 3a n is 2, R ‘s may be identical or different). a 3a a Another preferred embodiment of n and the substituent R is such that n is 0, 1 or 2, and R is a carbamoyl group, a carboxy group, a C haloalkylcarbonyl group, a C alkoxycarbonyl group, a mono-C alkylamino group, di-C alkylamino group, 1-6 1-3 1-3 mono-C alkylaminocarbonyl group, a di-C alkylaminocarbonyl group or a C 1-3 1-3 1-3 a 3a alkylcarbonylamino group (when n is 2, R ‘s may be identical or different). a 3a a A more preferred embodiment of n and the substituent R is such that n is 0 or 1, and R is a C alkyl group. a 3a a Another more preferred embodiment of n and the substituent R is such that n is 0 or 1, and R is a halogen atom. a 3a a Another more preferred embodiment of n and the substituent R is such that n is 0 or 1, and R is a cyano group. a 3a a Another more preferred embodiment of n and the substituent R is such that n is 0 or 1, and R is a hydroxy group. a 3a a Another more preferred embodiment of n and the substituent R is such that n 3a 3a is 2, and R is a halogen atom or a C alkyl group (R ‘s may be identical or different).

As favorable tricyclic pyrimidine compounds of the present invention for use as JAK inhibitors and as preventive, therapeutic and/or improving agent for diseases against which inhibition of JAK is effective, the following compounds may be mentioned. 1 ) Compounds represented by the formula (I ): 2a 2a 1a a (R ) a ( I ) [wherein R is a hydrogen atom or a halogen atom, a 9a 9a X is CR (wherein R is a hydrogen atom, a halogen atom, a cyano group, a C alkyl group, a C haloalkyl group or a C cycloalkyl group) or a nitrogen atom, 1-6 3-6 a 10a 10a Y is CR (wherein R is a hydrogen atom), a a a the ring A is represented by the following formula (II -1) or (II -2): ( II ) ( II -1 ) (II -2 ) 1a 4a 1a 5a 2a (wherein T is a nitrogen atom or CR , U is a nitrogen atom or CR , T is a single bond, and E is an oxygen atom or a sulfur atom), the ring B is a C cycloalkane, a C cycloalkene (a ring-constituting methylene 3-11 3-11 group of the C cycloalkane and the C cycloalkene may be replaced by a carbonyl 3-11 3-11 group), a 3 to 11-membered non-aromatic heterocycle, a C aromatic carbocycle or a 6-14 5 to 10-membered aromatic heterocycle, L is a single bond or a C alkylene group, L is a single bond, a C alkylene group, a C alkenylene group (the C alkylene 1-6 2-6 1-6 group and the C alkenylene group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, amino groups and cyano groups), =C(R )- (wherein 15a a 2a R is a hydrogen atom or a cyano group, and the bond connecting the ring B and L 15a 15a is a double bond) or =C(R )-CH - (wherein R is a hydrogen atom or a cyano group, a 2a and the bond connecting the ring B and L is a double bond),, 3a a a L is a single bond or represented by any of the following formulae (XIV -1) to (XIV -15) or (XIII ): R 12a a a a a a (XIV -1 ) (XIV -2 ) ( XIV -3 ) ( XIV -4 ) (XIV -5 ) (XIV ) N N O N 12a 13a R 12a 13a 12a a a a a a (XIV -6 ) ( XIV -7 ) ( XIV -8 ) (XIV -9 ) ( XIV -10 ) 1a 1a O O N S N O R 12a a a a a a ( XIV -11 ) ( XIV -12 ) (XIV -13 ) ( XIV -14 ) ( XIV -15 ) (wherein E is an oxygen atom or a sulfur atom), 3a 2a when L is a single bond, R is a hydrogen atom, a halogen atom, an azido group, a C cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a C aryl 3-11 6-14 group , a 5 to 10-membered aromatic heterocyclyl group, a 8 to 11-membered partially saturated aromatic cyclic group or a 8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon group (the C cycloalkyl group, the 3 to 11-membered non- 3-11 aromatic heterocyclyl group, the C aryl group , the 5 to 10-membered aromatic 6-14 heterocyclyl group, the 8 to 11-membered partially saturated aromatic cyclic group and the 8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of the substituent set V , the substituent set V and C alkyl groups (the C alkyl groups are substituted with a C 1-6 1-6 1-6 alkoxycarbonylamino group (the C alkoxycarbonylamino group is unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms))), 3a 2a when L is not a single bond, R is a hydrogen atom, a C alkyl group, a C alkenyl 1-6 2-6 group, a C alkynyl group (the C alkyl group, the C alkenyl group and the C 2-6 1-6 2-6 2-6 alkynyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V and the substituent set V ), a C cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a 3-11 C aryl group , a 5 to 10-membered aromatic heterocyclyl group, a 8 to 11-membered 6-14 partially saturated aromatic cyclic group or a 8 to 11-membered aromatic ring- condensed alicyclic hydrocarbon group (the C cycloalkyl group, the 3 to 11- 3-11 membered non-aromatic heterocyclyl group, the C aryl group , the 5 to 10-membered 6-14 aromatic heterocyclyl group, the 8 to 11-membered partially saturated aromatic cyclic group and the 8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon group are unsubstituted or substituted with one or more identical or different substituents 4a 9a independently selected from the substituent set V and the substituent set V ), n is 0, 1 or 2, R is a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a sulfamoyl group, a phosphono group, a phosphonooxy group, a sulfo group, a sulfoxy group, a tetrazolyl group, a halogen atom, a cyano group, a nitro group, a C alkyl group, a C haloalkyl group, a C cycloalkyl group, a C alkenyl group, a C 1-6 3-11 2-6 2-6 haloalkenyl group, a C alkoxy group, a C haloalkoxy group, a C alkylthio group, a 1-6 1-6 1-6 C haloalkylthio group, a C alkylcarbonyl group, a C haloalkylcarbonyl group, a C 1-6 1-6 1-6 1- alkylsulfonyl group, a C haloalkylsulfonyl group, a C alkoxycarbonyl group, a 6 1-6 1-6 mono-C alkylamino group, a di-C alkylamino group, a mono-C 1-6 1-6 1-6 40 alkylaminocarbonyl group, a di-C alkylaminocarbonyl group or a C 1-6 1-6 a 3a alkylcarbonylamino group (when n is 2, R ’s may be identical or different), 4a 5a each of R and R is independently a hydrogen atom, a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a tetrazolyl group, a halogen atom, a cyano group, a C alkyl group, a C alkenyl group, a C alkoxy group, a C alkylthio group, 1-6 2-6 1-6 1-6 a C alkylcarbonyl group, a C alkylsulfonyl group, a mono-C alkylamino group, a 1-6 1-6 1-6 di-C alkylamino group (the C alkyl group, the C alkenyl group, the C alkoxy 1-6 1-6 2-6 1-6 group, the C alkylthio group, the C alkylcarbonyl group, the C alkylsulfonyl group, 1-6 1-6 1-6 the mono-C alkylamino group and the di-C alkylamino group are unsubstituted or 1-6 1-6 substituted with one or more identical or different substituents independently selected from the substituent set V ), a C alkoxycarbonyl group, a C cycloalkyl group, a 3 1-6 3-11 to 11-membered non-aromatic heterocyclyl group, a C aryl group or a 5 to 10- 6-14 membered aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11- 3-11 membered non-aromatic heterocyclyl group, the C aryl group and the 5 to 10- 6-14 membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), R is a hydrogen atom, a C alkyl group (the C alkyl group is unsubstituted or 1-6 1-6 substituted with one or more identical or different substituents independently selected from the substituent set V ), a C cycloalkyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), 12a 13a each of R and R is independently a hydrogen atom, a C alkyl group, a C 1-6 1-6 haloalkyl group (the C alkyl group and the C haloalkyl group are unsubstituted or 1-6 1-6 substituted with one or more identical or different substituents independently selected 2a 8a 9a from the substituent set V , the substituent set V and the substituent set V ), a C 3-11 cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a C aryl 6-14 group , a 5 to 10-membered aromatic heterocyclyl group, a 8 to 14-membered partially saturated aromatic cyclic group or a 8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon group (the C cycloalkyl group, the 3 to 11-membered non- 3-11 aromatic heterocyclyl group, C aryl group , the 5 to 10-membered aromatic 6-14 heterocyclyl group, the 8 to 14-membered partially saturated aromatic cyclic group and the 8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon group are unsubstituted or substituted with one or more identical or different substituents 4a 9a independently selected from the substituent set V or the substituent set V )], tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a 1a 2 ) The compounds according to 1 ), wherein R is a hydrogen atom or a halogen atom, a 9a 9a X is CR (wherein R is a hydrogen atom, a halogen atom, a cyano group, a C alkyl group, a C haloalkyl group or a C cycloalkyl group) or a nitrogen atom, 1-6 3-6 a 10a 10a Y is CR (wherein R is a hydrogen atom), a a a the ring A is represented by the following formula (II -1) or (II -2): ( II ) ( II -1 ) (II -2 ) 1a 4a 1a 5a 2a (wherein T is a nitrogen atom or CR , U is a nitrogen atom or CR , T is a single 2a 6a bond, E is an oxygen atom or a sulfur atom, and R is a hydrogen atom, a C alkyl group (the C alkyl group is unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a C cycloalkyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7- membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V )), L is a single bond or a C alkylene group, L is a single bond, a C alkylene group or a C haloalkylene group (the C alkylene 1-6 1-6 1-6 group and the C haloalkylene group are unsubstituted or substituted with a hydroxy group or a cyano group), the ring B is a C cycloalkane, a C cycloalkene, a 3 to 11-membered non-aromatic 3-11 3-11 heterocycle, a C aromatic carbocycle or a 5 to 10-membered aromatic heterocycle, 6-14 a 3a n is 0 or 1, R is a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a tetrazolyl group, a halogen atom, a cyano group, a nitro group, a C alkyl group, a C haloalkyl group, a C cycloalkyl group, a C alkoxy group, a C 1-3 3-6 1-3 1-3 haloalkoxy group or a C alkylsulfonyl group, and 3a 2a L is a single bond, and R is a hydrogen atom, a halogen atom, a C cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6- membered aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), or 3a a a L is represented by any of the following formulae (V -1) to (V -11): 12 a R 12 E 1a a E O O a a a a a (V -1 ) (V -2 ) (V -3 ) (V -4 ) (V -5 ) (V -6 ) (V ) 12a 13a R a a 12 13 a a a a a (V -7 ) (V -8 ) (V -9 ) (V -10 ) (V -11 ) 1a 12a 13a (wherein E is an oxygen atom, and each of R and R is independently a hydrogen atom or a C alkyl group), and R is a hydrogen atom, a C alkyl group (the C alkyl 1-6 1-6 1-6 group is unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a C cycloalkyl group, a 4 to 7- membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non- aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), and 4a 5a each of R and R is independently a hydrogen atom, an amino group, a carbamoyl group, a halogen atom, a cyano group, a C alkyl group, a C haloalkyl 1-6 1-6 group, a C cycloalkyl group, a C alkoxy group, a C haloalkoxy group, a C 3-6 1-6 1-6 1-6 alkylsulfonyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a 1a 3 ) The compounds according to 2 ), wherein R is a hydrogen atom, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a a 10a 10a 4 ) The compounds according to 2 ) or 3 ), wherein Y is CR (wherein R is a hydrogen atom), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a a ) The compounds according to any one of 2 ) to 4 ), wherein X is a nitrogen atom or 9a 9a CR (wherein R is a hydrogen atom, a halogen atom or a cyano group), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a a 9a 9a 6 ) The compounds according to any one of 2 ) to 5 ), wherein X is CR (wherein R is a hydrogen atom), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a a 7 ) The compounds according to any one of 2 ) to 6 ), wherein the ring A is represented by any of the following formulae (IV -1) to (IV -3): N 2a (IV ) ( IV -1 ) ( IV -2 ) (IV -3 ) 2a 4a (wherein E is an oxygen atom or a sulfur atom, R is a hydrogen atom, an amino group, a carbamoyl group, a halogen atom, a cyano group, a C alkyl group, a C 1-6 1-6 haloalkyl group, a C cycloalkyl group, a C alkoxy group, a C haloalkoxy group, a 3-6 1-6 1-6 C alkylsulfonyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group, and R is a hydrogen atom, a C alkyl group, a C haloalkyl group, a C cycloalkyl group, a 4 to 7-membered non- 1-6 1-6 3-6 aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a a 8 ) The compounds according to any one of 2 ) to 7 ), wherein the ring A is represented by any of the following formulae (VIII -1) to (VIII -5): N N N N H C O S (VIII ) N N N N (VIII -4 ) (VIII -5 ) (VIII -3 ) (VIII -1 ) (VIII -2 ) tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a 1a 9 ) The compounds according to any one of 2 ) to 8 ), wherein L is a single bond, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a 2a ) The compounds according to any one of 2 ) to 9 ), wherein L is a single bond or a C alkylene group (the C alkylene group is unsubstituted or substituted with a cyano 1-3 1-3 group) or a C haloalkylene group, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a 2a 11 ) The compounds according to any one of 2 ) to 9 ), wherein L is a single bond or a methylene group, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a a 12 ) The compounds according to any one of 2 ) to 11 ), wherein the ring B is a C cycloalkane, benzene or a 4 to 7-membered non-aromatic heterocycle, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a a 13 ) The compounds according to any one of 2 ) to 11 ), wherein the ring B is cyclohexane, benzene or piperidine, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a a 14 ) The compounds according to any one of 2 ) to 11 ), wherein the ring B is spiro[2,5]octane or adamantane, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a a ) The compounds according to any one of 2 ) to 11 ), wherein the ring B is cyclohexane, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a a 3a 16 ) The compounds according to any one of 2 ) to 15 ), wherein n is 0 or 1, and R is a methyl group, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a a 3a 17 ) The compounds according to any one of 2 ) to 15 ), wherein n is 0 or 1, and R is a halogen atom, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a a 3a 18 ) The compounds according to any one of 2 ) to 15 ), wherein n is 0 or 1, and R is a cyano group, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a a 3a 19 ) The compounds according to any one of 2 ) to 15 ), wherein n is 0 or 1, and R is a hydroxy group, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a a ) The compounds according to any one of 2 ) to 15 ), wherein n is 0, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a 3a 21 ) The compounds according to any one of 2 ) to 20 ), wherein L is a single bond, and R is a hydrogen atom, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a 3a 22 ) The compounds according to any one of 2 ) to 20 ), wherein L is a single bond, and R is a halogen atom, tautomers or pharmaceutically acceptable salts of the 40 compounds or solvates thereof. a a a 3a 23 ) The compounds according to any one of 2 ) to 20 ), wherein L is a single bond, and R is a C cycloalkyl group or a 3 to 11-membered non-aromatic heterocyclyl group (the C cycloalkyl group and the 3 to 11-membered non-aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different 45 substituents independently selected from the group consisting of hydroxy groups, cyano groups, halogen atoms, carboxy groups, carbamoyl groups, C alkyl groups (the C 1-6 1-6 alkyl groups are unsubstituted or substituted with a hydroxy group or a cyano group), C haloalkyl groups, C haloalkoxy groups, di-C alkylamino groups, C 1-6 1-6 1-6 1-6 alkylsulfonyl groups, mono-C alkylaminocarbonyl groups, C alkylcarbonylamino 1-6 1-6 groups (the mono-C alkylaminocarbonyl groups and the C alkylcarbonylamino 1-6 1-6 groups are unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms), 4 to 7-membered non-aromatic heterocyclyl groups and phenyl groups (the phenyl groups are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms and C haloalkyl groups)), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a 3a 2a 24 ) The compounds according to 23 ) , wherein L is a single bond, and R is a cyclohexyl group or a cyclopentyl group (the cyclohexyl group and the cyclopentyl group are unsubstituted or substituted with a C alkyl group or a C haloalkyl group), 1-3 1-3 tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a 3a 2a 25 ) The compounds according to 23 ), wherein L is a single bond, and R is an azetidinyl group, a pyrrolidinyl group, a piperidinyl group, a morpholinyl group, a 1,1- dioxothiomorpholino group, a thiazolidinyl group, a piperadinyl group, an oxopiperadinyl group or a indolinyl group (the azetidinyl group, the pyrrolidinyl group, the piperidinyl group, the morpholinyl group, the 1,1-dioxothiomorpholino group, the thiazolidinyl group, the piperadinyl group, the oxopiperadinyl group and the indolinyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, cyano groups, halogen atoms, carboxy groups, carbamoyl groups, C alkyl groups (the C alkyl 1-6 1-6 groups are unsubstituted or substituted with a hydroxy group or a cyano group), C haloalkyl groups, C haloalkoxy groups, di-C alkylamino groups, C alkylsulfonyl 1-6 1-6 1-6 groups, mono-C alkylaminocarbonyl groups, C alkylcarbonylamino groups (the 1-6 1-6 mono-C alkylaminocarbonyl groups and the C alkylcarbonylamino groups are 1-6 1-6 unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms), 4 to 7-membered non-aromatic heterocyclyl groups and phenyl groups (the phenyl groups are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms and C haloalkyl groups)), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a 3a 26 ) The compounds according to any one of 2 ) to 20 ), wherein L is a single bond, and R is a phenyl group or a 5 to 10-membered aromatic heterocyclyl group (the phenyl group and the 5 to 10-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, cyano groups, carbamoyl groups, C alkyl 40 groups, C alkoxy groups, di-C alkylamino groups (the C alkyl groups, the C 1-6 1-3 1-6 1-6 alkoxy groups and the di-C alkylamino groups are unsubstituted or substituted with a hydroxy group or a cyano group), C alkylthio groups, C alkylsulfonyl groups, C 1-6 1-6 1-6 haloalkyl groups, C haloalkoxy groups, C haloalkylthio groups, 4 to 7-membered 1-6 1-6 non-aromatic heterocyclyl groups and 5 to 6-membered aromatic heterocyclyl groups), 45 tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a 3a 27 ) The compounds according to any one of 2 ) to 20 ), wherein L is a single bond, and R is a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one, two or three identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, cyano groups, C alkyl groups, C alkoxy groups, C alkylthio groups, mono-C alkylamino groups, 6 1-6 1-6 1-3 di-C alkylamino groups, C alkylsulfonyl groups (the C alkyl group, the C alkoxy 1-3 1-6 1-6 1-6 group, the C alkylthio group, the mono-C alkylamino group, the di-C alkylamino 1-6 1-3 1-3 group and the C alkylsulfonyl group are unsubstituted or substituted with a hydroxy group or a cyano group), C haloalkyl groups, C haloalkoxy groups, C 1-6 1-6 1-6 haloalkylthio groups and C haloalkylsulfonyl groups), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a 3a 2a 28 ) The compounds according to 27 ), wherein L is a single bond, and R is a phenyl group (the phenyl group is unsubstituted or substituted with one, two or three identical or different substituents independently selected from the group consisting of halogen atoms, cyano groups, C alkyl groups, C alkoxy groups (the C alkoxy group is 1-3 1-3 1-3 unsubstituted or substituted with a hydroxy group or a cyano group), C alkylthio groups, C alkylsulfonyl groups, C haloalkyl groups, C haloalkoxy groups, C 1-3 1-3 1-3 1-3 haloalkylthio groups, di-C alkylamino groups (the di-C alkylamino groups are 1-3 1-3 unsubstituted or substituted with a cyano group), carbamoyl groups and 5 to 6- membered aromatic heterocyclyl groups), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a 3a 2a 29 ) The compounds according to 27 ), wherein L is a single bond, and R is a furanyl group, a thienyl group, a pyrazolyl group, an isoxazolyl group, a thiazolyl group, a thiadiazolyl group, an indazolyl group, a quinoxalinyl group, an oxazolyl group, a benzothiazolyl group, a triazolyl group or a pyridinyl group (the furanyl group, the thienyl group, the pyrazolyl group, the isoxazolyl group, the thiazolyl group, the thiadiazolyl group, the indazolyl group, the quinoxalinyl group, the oxazolyl group, the benzothiazolyl group, the triazolyl group and the pyridinyl group are unsubstituted or substituted with identical or different one, two or three substituents independently selected from the group consisting of halogen atoms, cyano groups, C alkyl groups (the C alkyl groups are unsubstituted or substituted with a hydroxy group), C 1-3 1-3 haloalkyl groups, hydroxy groups, C alkoxy groups, 4 to 7-membered non-aromatic heterocyclyl group and C haloalkoxy groups), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a 3a ) The compounds according to any one of 2 ) to 20 ), wherein L is represented by the following formula (XI -1) or (XI -2): ( XI ) (XI -1) ( XI -2) , and R is a methyl group (the methyl group is unsubstituted or substituted with a cyano groups or a phenyl group), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a 3a 40 31 ) The compounds according to any one of 2 ) to 20 ), wherein L is represented by the formula (X -1): (X -1) , and R is a hydrogen atom, a C alkyl group (the C alkyl group is unsubstituted or 1-3 1-3 substituted with a cyano group), a C haloalkyl group, a 4 to 7-membered non- aromatic heterocyclyl group or a phenyl group (the 4 to 7-membered non-aromatic heterocyclyl group and the phenyl group are unsubstituted or substituted with a substituent selected from the group consisting of a hydroxy group, a halogen atom, a C alkyl group and a C haloalkyl group), tautomers or pharmaceutically acceptable 1-3 1-3 salts of the compounds or solvates thereof. a a a 3a 32 ) The compounds according to any one of 2 ) to 20 ), wherein L is represented by the formula (X -10): (X -10) 1a 11a 11a 2a (wherein E is NR (wherein R is a hydroxy group)), and R is a hydrogen atom, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a 3a 33 ) The compounds according to any one of 2 ) to 20 ), wherein L is represented by the formula (X -2): (X -2) , and R is a C alkyl group (the C alkyl group is unsubstituted or substituted with a 1-6 1-6 phenyl group), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a 3a 34 ) The compounds according to any one of 2 ) to 20 ), wherein L is represented by the formula (X -3): (X -3) , and R is a hydrogen atom, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a 3a 35 ) The compounds according to any one of 2 ) to 20 ), wherein L is represented by the formula (X -3): (X -3) , and R is a C alkyl group, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a 3a 36 ) The compounds according to any one of 2 ) to 20 ), wherein L is represented by the formula (X -4): S (X -4) , and R is a C alkyl group, a C haloalkyl group, a C cycloalkyl group or a phenyl 1-3 1-3 3-6 group (the phenyl group is unsubstituted or substituted with a halogen atom), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a 3a 37 ) The compounds according to any one of 2 ) to 20 ), wherein L is represented by the formula (X -7): ( X-7 ) 12a 2a (wherein R is a hydrogen atom), and R is a hydrogen atom, a C alkyl group, a C 1-6 1- haloalkyl group (the C alkyl group and the C haloalkyl group are unsubstituted or 6 1-6 1-6 substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, cyano groups and phenyl groups (the phenyl groups are unsubstituted or substituted with a halogen atom or a cyano group)), a C cycloalkyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with a substituent selected from the group consisting of a C alkyl group, a C haloalkyl group and a halogen atom), 1-3 1-3 tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a 3a 38 ) The compounds according to any one of 2 ) to 20 ), wherein L is represented by the formula (XVI ) (XVI ) (wherein R is a hydrogen atom, a C alkyl group or C haloalkyl group), and 1-6 1-6 R is a hydrogen atom, a C alkyl group, a C haloalkyl group (the C alkyl group 1-6 1-6 1-6 and the C haloalkyl group are unsubstituted or substituted with a substituent selected from the group consisting of a hydroxy group, a cyano group, a C alkoxy group, mono-C alkylaminocarbonyl group (the mono-C alkylaminocarbonyl group is 1-3 1-3 unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms), a C cycloalkyl group, a 4 to 7-membered non- aromatic heterocyclyl group, a phenyl group and a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms, cyano groups, hydroxy groups, C alkoxy groups, C haloalkoxy groups, C haloalkylsulfonyl 1-3 1-3 1-3 groups, C alkoxycarbonyl groups, 4 to 7-membered non-aromatic heterocyclyl groups and phenyl groups (the phenyl groups are unsubstituted or substituted with a halogen atom))), a C cycloalkyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group and the to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one 40 or two identical or different substituents independently selected from the group consisting of hydroxy groups, halogen atoms, cyano groups, C alkyl groups (the C 1-3 1-3 alkyl groups are unsubstituted or substituted with a substituent selected from the group consisting of a hydroxy group, a cyano group and a C alkoxy group), C haloalkyl 1-3 1-3 groups, C alkoxy groups, C haloalkoxy groups, C haloalkylsulfonyl groups, 4 to 7- 1-3 1-3 1-3 membered non-aromatic heterocyclyl groups and phenyl groups (the phenyl groups are unsubstituted or substituted with a halogen atom)), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a 3a 39 ) The compounds according to any one of 2 ) to 20 ), wherein L is represented by the formula (XVI ): (XVI ) 12a 2a (wherein R is a hydrogen atom or a C alkyl group), and R is a hydrogen atom, a C alkyl group or a C haloalkyl group (the C alkyl group and the C haloalkyl 1-6 1-6 1-6 1-6 group are substituted with a substituent selected from the group consisting of a hydroxy group and a cyano group and with a substituent selected from the group consisting of a phenyl group and a 5 to 6-membered aromatic heterocyclyl group (the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms, cyano groups, C alkoxy groups and C alkylthio 1-3 1-3 groups)), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a 3a 40 ) The compounds according to any one of 2 ) to 20 ), wherein L is represented by the formula (X -11): (X -11) 12a 2a (wherein R is a hydrogen atom, a C alkyl group or a C haloalkyl group), and R 1-3 1-3 is a C alkyl group (the C alkyl group is unsubstituted or substituted with a cyano 1-6 1-6 group) or a C haloalkyl group, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a 3a 41 ) The compounds according to any one of 2 ) to 20 ), wherein L is represented by the formula (X -12): ( X -12 ) 12a 2a (wherein R is a hydrogen atom or a C alkyl group), and R is a C alkyl group 1-3 1-6 (the C alkyl group is unsubstituted or substituted with a cyano group), a C haloalkyl 1-6 1-6 group or a C cycloalkyl group, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a 3a 42 ) The compounds according to any one of 2 ) to 20 ), wherein L is represented by the formula (X -13): 12a 2a (wherein R is a hydrogen atom), and R is a C alkyl group, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a 1a 43 ) The compounds according to 1 ), wherein R is a hydrogen atom, a 9a 9a X is CR (wherein R is a hydrogen atom), a 10a 10a Y is CR (wherein R is a hydrogen atom), a a a the ring A is represented by any of the following formulae (VIII -1) to (VIII -5): N N N N H C O S (VIII ) N N N N (VIII -4 ) (VIII -5 ) (VIII -1 ) (VIII -2 ) (VIII -3 ) L is a single bond, the ring B is a C cycloalkane, (a ring-constituting methylene group of the C 4-7 4-7 cycloalkane may be replaced by a carbonyl group) or a 4 to 7-membered non-aromatic heterocycle, n is 0 or 1, R is a hydroxy group, a cyano group, a halogen atom or a C alkyl group, L is a single bond, a C alkylene group (the C alkylene group is unsubstituted or 1-6 1-6 substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups and cyano groups), a C haloalkylene group, a C alkenylene group (the C haloalkylene group and the C alkenylene 2-6 1-6 2-6 group are unsubstituted or substituted with one or two cyano groups), =C(R )- 15a a (wherein R is a hydrogen atom or a cyano group, and thebond connecting the ring B 2a 15a 15a and L is a double bond) or =C(R )-CH - (wherein R is a hydrogen atom or a cyano a 2a group, and the bond connecting the ring B and L is a double bond), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a 44 ) The compounds according to 43 ), wherein the ring B is cyclohexane or piperidine, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a 2a 45 ) The compounds according to 43 ), wherein L is a single bond, a C alkylene, a C alkenylene group (the C alkylene group and the C alkenylene group are 2-3 1-3 2-3 unsubstituted or substituted with one or two cyano groups) or a C haloalkylene group, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a 46 ) The compounds according to 43 ), wherein n is 0, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a a 3a 47 ) The compounds according to any one of 1 ) or 43 ) to 46 ), wherein L is a single bond, R is a hydrogen atom, a halogen atom, an azido group, a 3 to 11-membered non- aromatic heterocyclyl group, a phenyl group, a 5 to 10-membered aromatic heterocyclyl group or a 8 to 11-membered partially saturated aromatic cyclic group (the 3 to 11- membered non-aromatic heterocyclyl group, the phenyl group, the 5 to 10-membered aromatic heterocyclyl group and the 8 to 11-membered partially saturated aromatic cyclic group are unsubstituted or substituted with one, two or three identical or different substituents independently selected from the group consisting of hydroxy groups, amino groups, halogen atoms, cyano groups, nitro groups, carbamoyl groups, sulfamoyl groups, C alkyl groups, C haloalkyl groups, C alkoxy groups, C haloalkoxy 1-6 1-6 1-6 1-6 groups, mono-C alkylamino groups, di-C alkylamino groups, C alkylthio groups, 1-6 1-6 1-6 C haloalkylthio groups, C alkylcarbonyl groups, C haloalkylcarbonyl groups, C 1-6 1-6 1-6 1-6 alkylsulfonyl groups, C haloalkylsulfonyl groups, mono-C alkylaminosulfonyl groups, 1-6 1-6 di-C alkylaminosulfonyl groups, C alkoxycarbonyl groups, mono-C 1-6 1-6 1-6 alkylaminocarbonyl groups, di-C alkylaminocarbonyl groups, C alkylcarbonylamino 1-6 1-6 groups, C alkoxycarbonylamino groups (the C alkoxycarbonyl groups, the mono-C 1-6 1-6 1- alkylaminocarbonyl groups, the di-C alkylaminocarbonyl groups, the C 6 1-6 1-6 alkylcarbonylamino groups and the C alkoxycarbonylamino groups are unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms), C cycloalkyl groups, 4 to 7-membered non-aromatic heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a a 2a 48 ) The compounds according to any one of 1 ) or 43 ) to 46 ), wherein R is a 3 to 11-membered non-aromatic heterocyclyl group (the 3 to 11-membered non-aromatic heterocyclyl group is unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of cyano groups, halogen atoms, hydroxy groups, amino groups, carbamoyl groups, sulfamoyl groups, C alkyl groups (the C alkyl groups are unsubstituted or substituted with a substituent selected from the group consisting of a cyano group, a hydroxy group and a C alkoxycarbonylamino group), C haloalkyl groups, C alkoxy groups, mono-C 1-3 1-3 1-3 alkylamino groups, di-C alkylamino groups, C alkylsulfonyl groups, mono-C 1-3 1-3 1-3 alkylaminocarbonyl groups, di-C alkylaminocarbonyl groups, mono-C 1-3 1-3 alkylaminosulfonyl groups, di-C alkylaminosulfonyl groups, C alkylcarbonylamino 1-3 1-3 groups and C alkoxycarbonylamino groups (the C alkoxy groups, the mono-C 1-6 1-3 1-3 alkylamino groups, the di-C alkylamino groups, the C alkylsulfonyl groups, the 1-3 1-3 mono-C alkylaminocarbonyl groups, the di-C alkylaminocarbonyl groups, the mono- 1-3 1-3 C alkylaminosulfonyl groups, the di-C alkylaminosulfonyl groups, the C 1-3 1-3 1-3 alkylcarbonylamino groups and the C alkoxycarbonylamino groups are unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms or with a cyano group)), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a a 3a 49 ) The compounds according to any one of 1 ) or 43 ) to 46 ), wherein L is 40 represented by the formulae (XVI ): (XVI ) (wherein R is a hydrogen atom, a C alkyl group (the C alkyl group is 1-3 1-3 unsubstituted or substituted with a substituent selected from the group consisting of a hydroxy group, a cyano group, a C alkoxy group, a C cycloalkyl group and a phenyl 1-3 3-6 group), a C haloalkyl group, a C cycloalkyl group or a phenyl group (the phenyl 1-3 3-6 group is unsubstituted or substituted with a halogen atom or a cyano group)), and R is a hydrogen atom, a C alkyl group (the C alkyl group is unsubstituted or 1-6 1-6 substituted with a substituent selected from the group consisting of a hydroxy group, a cyano group, a C alkoxy group, a mono-C alkylaminocarbonyl group (the C 1-3 1-3 1-3 alkoxy group and the mono-C alkylaminocarbonyl group are unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms), a C cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a phenyl group and a 5 to 10-membered aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 10-membered aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms, cyano groups, C alkyl groups, C haloalkyl groups, C 1-3 1-3 1-3 alkoxy groups, C haloalkoxy groups, C alkylthio groups, C haloalkylthio groups, 1-3 1-3 1-3 C haloalkylsulfonyl groups and 4 to 7-membered non-aromatic heterocyclyl groups)), a C haloalkyl group, a C alkynyl group, a C cycloalkyl group, a 3 to 11-membered 1-6 2-6 3-6 non-aromatic heterocyclyl group, a phenyl group, a naphthyl group, a 5 to 10-membered aromatic heterocyclyl group, a 8 to 11-membered partially saturated aromatic cyclic group or a 8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon group (the C cycloalkyl group, the 3 to 11-membered non-aromatic heterocyclyl group, the phenyl group, the naphthyl group, the 5 to 10-membered aromatic heterocyclyl group, the 8 to 11-membered partially saturated aromatic cyclic group and the 8 to 11- membered aromatic ring-condensed alicyclic hydrocarbon group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, halogen atoms, cyano groups, C alkyl groups, C haloalkyl groups, C alkoxy groups, C haloalkoxy groups, C alkylthio 1-3 1-3 1-3 1-3 groups, C haloalkylthio groups, C haloalkylsulfonyl groups and 4 to 7-membered 1-3 1-3 non-aromatic heterocyclyl groups), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a a 3a 50 ) The compounds according to any one of 1 ) or 43 ) to 46 ), wherein L is represented by any of the following formulae (XX -1) to (XX -3): (wherein R is a hydrogen atom, a C alkyl group (the C alkyl group is 1-3 1-3 unsubstituted or substituted with a cyano group) or a C haloalkyl group), and R is a hydrogen atom, a C alkyl group or a C haloalkyl group (the C alkyl group and the 1-3 1-3 1-3 C haloalkyl group are substituted with a substituent selected from the group consisting of a hydroxy group and a cyano group and with a substituent selected from the group consisting of a 3 to 11-membered non-aromatic heterocyclyl group, a phenyl 40 group and a 5 to 10-membered aromatic heterocyclyl group (the 3 to 11-membered non- aromatic heterocyclyl group, the phenyl group and the 5 to 10-membered aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms, cyano groups, C alkyl groups, C haloalkyl groups, C alkoxy groups and C alkylthio 1-3 1-3 1-3 1-3 groups)), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a a 3a 51 ) The compounds according to any one of 1 ) or 43 ) to 46 ), wherein L is represented by any of the following formulae (XXVI -1) to (XXVI -5): 1a 12a (wherein E is an oxygen atom, R is a C alkyl group (the C alkyl group is 1-6 1-6 unsubstituted or substituted with a substituent selected from the group consisting of a cyano group, a hydroxy group, a C alkoxy group, a C cycloalkyl group and a phenyl 1-3 3-6 group), a C haloalkyl group, a C cycloalkyl group or a phenyl group (the phenyl 1-6 3-6 group is unsubstituted or substituted with a halogen atom or a cyano group)), and R is a C alkyl group (the C alkyl group is unsubstituted or substituted with a 1-6 1-6 substituent selected from the group consisting of a cyano group, a hydroxy group, a C alkoxy group, a C cycloalkyl group and a phenyl group), a C haloalkyl group, a C 3-6 1-6 3-6 cycloalkyl group or a phenyl group (the phenyl group is unsubstituted or substituted with a halogen atom)), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a a 3a 52 ) The compounds according to any one of any one of 1 ) or 43 ) to 46 ), wherein L is represented by the formula (X -11): (X -11) (wherein R is a hydrogen atom, a C alkyl group (the C alkyl group is 1-3 1-3 unsubstituted or substituted with a cyano group or a 5 to 6-membered aromatic heterocyclyl group (the 5 to 6-membered aromatic heterocyclyl group is unsubstituted or substituted with a C alkyl group)), a C haloalkyl group or a C cycloalkyl group), 1-3 1-3 3-6 and R is a C alkyl group (the C alkyl group is unsubstituted or substituted with a 1-3 1-3 cyano group) or a C haloalkyl group, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a a 3a 53 ) The compounds according to any one of 1 ) or 43 ) to 46 ), wherein L is represented by the formula (X -5): ( X -5) , and R is a C alkyl group, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a a 3a 54 ) The compounds according to any one of 1 ) or 43 ) to 46 ), wherein L is represented by the formula (X -6): (X -6) , and R is a hydrogen atom, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a a 3a 55 ) The compounds according to any one of 1 ) or 43 ) to 46 ), wherein L is represented by the formula (XVIII ): (XVIII ) 12a 2a (wherein R is a hydrogen atom), and R is a C alkyl group (the C alkyl group is 1-6 1-6 unsubstituted or substituted with a phenyl group), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a a 3a 56 ) The compounds according to any one of 1 ) or 43 ) to 46 ), wherein L is represented by the formula (X -8): , and R is a C alkyl group, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. a a a a a 57 ) The compounds according to any one of 1 ), 2 ) or 43 ) to 56 ), which is represented by the following formula (XXII -1) or (XXII -2): 3a a 3a a (R ) n a (R ) ( XXII ) ( XXII -1 ) ( XXII -2 ) tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. 58 ) Compounds represented by the formula (XII ): (XII ) a 9a 9a wherein X is CR (wherein R is a hydrogen atom, a halogen atom or a cyano group), a 1a a and the rings A and B are any of the following combinations shown in Table 1, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof.

The symbols in Table 1 denote the following substituents.

TABLE 1 ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― － ― ― ― ― ― ａ１ａａ１ａａ１ａａ１ａＡＢＡＢＡＢＡＢ ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― － ― ― ― ― ― １１１１Ａ１Ｂ１Ａ１Ｂ３Ａ１Ｂ５Ａ１Ｂ７１１１１Ａ２Ｂ１Ａ２Ｂ３Ａ２Ｂ５Ａ２Ｂ７１１１１Ａ３Ｂ１Ａ３Ｂ３Ａ３Ｂ５Ａ３Ｂ７１１１１Ａ４Ｂ１Ａ４Ｂ３Ａ４Ｂ５Ａ４Ｂ７１１１１Ａ５Ｂ１Ａ５Ｂ３Ａ５Ｂ５Ａ５Ｂ７１１１１Ａ６Ｂ１Ａ６Ｂ３Ａ６Ｂ５Ａ６Ｂ７１１１１Ａ７Ｂ１Ａ７Ｂ３Ａ７Ｂ５Ａ７Ｂ７１１１１Ａ８Ｂ１Ａ８Ｂ３Ａ８Ｂ５Ａ８Ｂ７１１１１Ａ１Ｂ２Ａ１Ｂ４Ａ１Ｂ６Ａ１Ｂ８１１１１Ａ２Ｂ２Ａ２Ｂ４Ａ２Ｂ６Ａ２Ｂ８１１１１Ａ３Ｂ２Ａ３Ｂ４Ａ３Ｂ６Ａ３Ｂ８１１１１Ａ４Ｂ２Ａ４Ｂ４Ａ４Ｂ６Ａ４Ｂ８１１１１Ａ５Ｂ２Ａ５Ｂ４Ａ５Ｂ６Ａ５Ｂ８１１１１Ａ６Ｂ２Ａ６Ｂ４Ａ６Ｂ６Ａ６Ｂ８１１１１Ａ７Ｂ２Ａ７Ｂ４Ａ７Ｂ６Ａ７Ｂ８１１１１Ａ８Ｂ２Ａ８Ｂ４Ａ８Ｂ６Ａ８Ｂ８ ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― ― － ― ― ― ― ― 59 ) Compounds represented by the formula (XII -1): (XII -1 ) a 9a 9a wherein X is CR (wherein R is a hydrogen atom, a halogen atom or a cyano group), a 2a a and the rings A and B are any of the following combinations shown in Table 2 , tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof.

The symbols in Table 2 denote the following substituents.

TABLE 2 ― ― ― ― ― ― ― ― ―― ― ― ― ― ― ― ― ― ― ― ― ― ―― ― ― ― － ― ― ― ― ― ａ２ａａ２ａａ２ａａ２ａＡＢＡＢＡＢＡＢ ― ― ― ― ― ― ― ― ―― ― ― ― ― ― ― ― ― ― ― ― ― ―― ― ― ― － ― ― ― ― ― ２２２２Ａ１Ｂ１Ａ１Ｂ３Ａ１Ｂ５Ａ１Ｂ７２２２２Ａ２Ｂ１Ａ２Ｂ３Ａ２Ｂ５Ａ２Ｂ７２２２２Ａ３Ｂ１Ａ３Ｂ３Ａ３Ｂ５Ａ３Ｂ７２２２２Ａ４Ｂ１Ａ４Ｂ３Ａ４Ｂ５Ａ４Ｂ７２２２２Ａ５Ｂ１Ａ５Ｂ３Ａ５Ｂ５Ａ５Ｂ７２２２２Ａ６Ｂ１Ａ６Ｂ３Ａ６Ｂ５Ａ６Ｂ７２２２２Ａ７Ｂ１Ａ７Ｂ３Ａ７Ｂ５Ａ７Ｂ７２２２２Ａ８Ｂ１Ａ８Ｂ３Ａ８Ｂ５Ａ８Ｂ７２２２２Ａ１Ｂ２Ａ１Ｂ４Ａ１Ｂ６Ａ１Ｂ８２２２２Ａ２Ｂ２Ａ２Ｂ４Ａ２Ｂ６Ａ２Ｂ８２２２２Ａ３Ｂ２Ａ３Ｂ４Ａ３Ｂ６Ａ３Ｂ８２２２２Ａ４Ｂ２Ａ４Ｂ４Ａ４Ｂ６Ａ４Ｂ８２２２２Ａ５Ｂ２Ａ５Ｂ４Ａ５Ｂ６Ａ５Ｂ８２２２２Ａ６Ｂ２Ａ６Ｂ４Ａ６Ｂ６Ａ６Ｂ８２２２２Ａ７Ｂ２Ａ７Ｂ４Ａ７Ｂ６Ａ７Ｂ８２２２２Ａ８Ｂ２Ａ８Ｂ４Ａ８Ｂ６Ａ８Ｂ８ 60 ) Compounds represented by the formula (XII -2): (XII -2 ) a 9a 9a wherein X is CR (wherein R is a hydrogen atom, a halogen atom or a cyano group), a 3a a and the rings A and B are any of the following combinations shown in Table 3, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof.

The symbols in Table 3 denote the following substituents.

TABLE 3 ― ― ― ― ― ― ― ― ―― ― ― ― ― ― ― ― ― ― ― ― ― ―― ― ― ― － ― ― ― ― ― ａ３ａａ３ａａ３ａａ３ａＡＢＡＢＡＢＡＢ ― ― ― ― ― ― ― ― ―― ― ― ― ― ― ― ― ― ― ― ― ― ―― ― ― ― － ― ― ― ― ― ３３３３Ａ１Ｂ１Ａ１Ｂ３Ａ１Ｂ５Ａ１Ｂ７３３３３Ａ２Ｂ１Ａ２Ｂ３Ａ２Ｂ５Ａ２Ｂ７３３３３Ａ３Ｂ１Ａ３Ｂ３Ａ３Ｂ５Ａ３Ｂ７３３３３Ａ４Ｂ１Ａ４Ｂ３Ａ４Ｂ５Ａ４Ｂ７３３３３Ａ５Ｂ１Ａ５Ｂ３Ａ５Ｂ５Ａ５Ｂ７３３３３Ａ６Ｂ１Ａ６Ｂ３Ａ６Ｂ５Ａ６Ｂ７３３３３Ａ７Ｂ１Ａ７Ｂ３Ａ７Ｂ５Ａ７Ｂ７３３３３Ａ８Ｂ１Ａ８Ｂ３Ａ８Ｂ５Ａ８Ｂ７３３３３Ａ１Ｂ２Ａ１Ｂ４Ａ１Ｂ６Ａ１Ｂ８３３３３Ａ２Ｂ２Ａ２Ｂ４Ａ２Ｂ６Ａ２Ｂ８３３３３Ａ３Ｂ２Ａ３Ｂ４Ａ３Ｂ６Ａ３Ｂ８３３３３Ａ４Ｂ２Ａ４Ｂ４Ａ４Ｂ６Ａ４Ｂ８３３３３Ａ５Ｂ２Ａ５Ｂ４Ａ５Ｂ６Ａ５Ｂ８３３３３Ａ６Ｂ２Ａ６Ｂ４Ａ６Ｂ６Ａ６Ｂ８３３３３Ａ７Ｂ２Ａ７Ｂ４Ａ７Ｂ６Ａ７Ｂ８３３３３Ａ８Ｂ２Ａ８Ｂ４Ａ８Ｂ６Ａ８Ｂ８ ― ― ― ― ― ― ― ― ―― ― ― ― ― ― ― ― ― ― ― ― ― ―― ― ― ― － ― ― ― ― ― 61 ) Compounds represented by the formula (XII -3): (XII -3 ) a 9a 9a wherein X is CR (wherein R is a hydrogen atom, a halogen atom or a cyano group), a 4a a the rings A and B are any of the following combinations shown in Table 4, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof.

The symbols in Table 4 denote the following substituents.

TABLE 4 ― ― ― ― ― ― ― ― ―― ― ― ― ― ― ― ― ― ― ― ― ― ―― ― ― ― － ― ― ― ― ― ａ４ａａ４ａａ４ａａ４ａＡＢＡＢＡＢＡＢ ― ― ― ― ― ― ― ― ―― ― ― ― ― ― ― ― ― ― ― ― ―― ― ― ― ― － ― ― ― ― ― ４４４４Ａ１Ｂ１Ａ１Ｂ３Ａ１Ｂ５Ａ１Ｂ７４４４４Ａ２Ｂ１Ａ２Ｂ３Ａ２Ｂ５Ａ２Ｂ７４４４４Ａ３Ｂ１Ａ３Ｂ３Ａ３Ｂ５Ａ３Ｂ７４４４４Ａ４Ｂ１Ａ４Ｂ３Ａ４Ｂ５Ａ４Ｂ７４４４４Ａ５Ｂ１Ａ５Ｂ３Ａ５Ｂ５Ａ５Ｂ７４４４４Ａ６Ｂ１Ａ６Ｂ３Ａ６Ｂ５Ａ６Ｂ７４４４４Ａ７Ｂ１Ａ７Ｂ３Ａ７Ｂ５Ａ７Ｂ７４４４４Ａ８Ｂ１Ａ８Ｂ３Ａ８Ｂ５Ａ８Ｂ７４４４４Ａ１Ｂ２Ａ１Ｂ４Ａ１Ｂ６Ａ１Ｂ８４４４４Ａ２Ｂ２Ａ２Ｂ４Ａ２Ｂ６Ａ２Ｂ８４４４４Ａ３Ｂ２Ａ３Ｂ４Ａ３Ｂ６Ａ３Ｂ８４４４４Ａ４Ｂ２Ａ４Ｂ４Ａ４Ｂ６Ａ４Ｂ８４４４４Ａ５Ｂ２Ａ５Ｂ４Ａ５Ｂ６Ａ５Ｂ８４４４４Ａ６Ｂ２Ａ６Ｂ４Ａ６Ｂ６Ａ６Ｂ８４４４４Ａ７Ｂ２Ａ７Ｂ４Ａ７Ｂ６Ａ７Ｂ８４４４４Ａ８Ｂ２Ａ８Ｂ４Ａ８Ｂ６Ａ８Ｂ８ ― ― ― ― ― ― ― ― ―― ― ― ― ― ― ― ― ― ― ― ― ― ―― ― ― ― － ― ― ― ― ― 62 ) The compounds with the combinations of substituents as defined in any of 58 ) to 61 ), wherein X is converted to a nitrogen atom, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof.

Next, the tricyclic pyridine compounds of the present invention represented by the formula (I ) will be described.

First, how the ring A is fused in the tricyclic pyridine compounds of the present invention will be described.

As is indicated in the formula (I ), the ring A is fused to the pyridine ring so as to 1b b have two carbon atoms in common and attached to L via a nitrogen atom in the ring A in the formula (I ).

(R ) b ( I ) Therefore, when the ring A is represented by the formula (II ), (II ) the molecule of the compounds as a whole is represented by the formula (I )-2, 1b 1b W L B (R ) b ( I ) -2 1b N and when the ring A is represented by the formula (III ), (III ) the molecule as a whole is represented by the formula (I )-3,. 2b 2b 2b 1b b W L B (R ) b ( I ) -3 1b N and when the ring A is represented by the formula (IV ), 3b ( IV ) the molecule as a whole is represented by the formula (I )-4. 3b 1b W L B (R ) b 3b n ( I ) -4 1b N In the present invention, the formulae representing L indicate that the left ends of 2b 2b the formulae are bonded to L , and the right ends of the formulae are bonded to R . 1b 2b 3b b In the present invention, L , L and R may be bounded to the ring B in the formula (I ) at any positions of the ring B without any particular restrictions.

Next, preferred structures of the respective substituents will be mentioned.

A more preferred embodiment of the substituent R is a hydrogen atom. b 15b A preferred embodiment of the substituent X is a nitrogen atom or CR (wherein R is a hydrogen atom, a halogen atom, a cyano group, a C alkyl group, a C 1-6 1-6 haloalkyl group or a C cycloalkyl group). b 15b A more preferred embodiment of the substituent X is a nitrogen atom or CR (wherein R is a hydrogen atom). b 15b 15b Another more preferred embodiment of the substituent X is CR (wherein R is a halogen atom). b 15b 15b A further preferred embodiment of the substituent X is CR (wherein R is a hydrogen atom). b 16b 16b A preferred embodiment of the substituent Y is CR (wherein R is a hydrogen atom).

A preferred embodiment of the ring A is represented by the following formula (IX - 1) or (IX -2): b 8b b 6b ( IX ) ( IX -1 ) (IX -2 ) 2b 17b 6b 8b (wherein E is an oxygen atom, a sulfur atom or NR , and each of R and R is independently a hydrogen atom, an amino group, a carbamoyl group, a halogen atom, a cyano group, a C alkyl group, a C alkoxy group, a C alkylsulfonyl group (the C 1-6 1-6 1-6 1-6 alkyl group, the C alkoxy group and the C alkylsulfonyl group are unsubstituted or 1-6 1-6 substituted with one or more identical or different substituents independently selected from the substituent set V ), a C cycloalkyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V )).

Another preferred embodiment of the ring A is represented by any of the following formulae (X -1) to (X -10): 8b 8b 2b R R E N N N N N N 2b 4 b b b b b ( X -1 ) ( X -2 ) ( X -3 ) (X -4 ) ( X -5 ) (X ) b b b b b 2 9 2 2 2 E R E E E 10 N N N N O N S N b b b 4 4 4 R R R 5b E b b b 5 5 R R R b b b b b (X -6 ) ( X -7 ) (X -8 ) ( X -9 ) (X -10 ) 2b 17b 4b 5b 6b 8b (wherein E is an oxygen atom, a sulfur atom or NR , and each of R , R , R , R and R is independently a hydrogen atom, an amino group, a carbamoyl group, a halogen atom, a cyano group, a C alkyl group, a C alkoxy group, a C 1-6 1-6 1-6 alkylcarbonyl group, a C alkylsulfonyl group (the C alkyl group, the C alkoxy 1-6 1-6 1-6 group, the C alkylcarbonyl group and the C alkylsulfonyl group are unsubstituted or 1-6 1-6 substituted with one or more identical or different substituents independently selected from the substituent set V ), a C cycloalkyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected 1b 10b from the substituent set V ), and R is a hydrogen atom, a C alkyl group (the C 1-6 1-6 alkyl group is unsubstituted or substituted with one or more identical or different substituents independently selected from substituent set V ), a C cycloalkyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6- membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V )).

A more preferred embodiment of the ring A is represented by the following formula (IX -1) or (IX -2): b 6b ( IX ) ( IX -1 ) (IX -2 ) 2b 6b 8b (wherein E is an oxygen atom, each of R and R is independently a hydrogen atom, a halogen atom or a C alkyl group).

Another more preferred embodiment of the ring A is represented by any of the following formulae (XXIII -1) to (XXIII -5): b b 2 (XXIII -3 ) (XXIII -2 ) (XXIII -1 ) 2 9b E 8 ( XXIII ) (XXIII -4 ) (XXIII -5 ) 2b 4b 5b 8b 9b (wherein E is an oxygen atom, each of R , R , R and R is independently a hydrogen atom, a halogen atom or a C alkyl group, and R is a hydrogen atom or a C alkyl group).

Another more preferred embodiment of the ring A is represented by the formula (XXIV ): (XXIV ) (wherein R is a hydrogen atom or a C alkyl group).

Another more preferred embodiment of the ring A is represented by the formula (XXIV ): (XXIV ) (wherein R is a C alkyl group (the C alkyl group is unsubstituted or substituted 1-6 1-6 with one or two identical or different substituents independently selected from the group consisting of cyano groups, hydroxy groups, C alkoxy groups, C alkylthio groups, 1-3 1-3 di-C alkylamino groups, di-C alkylaminocarbonyl groups, C cycloalkyl groups, 4 to 1-3 1-3 3-6 7-membered non-aromatic heterocyclyl groups, phenyl groups, and 5 to 6-membered aromatic heterocyclyl groups (the phenyl groups and the 5 to 6-membered aromatic heterocyclyl groups are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms, C alkyl groups and C haloalkyl groups)), a C haloalkyl group, a C cycloalkyl group 1-3 1-6 3-6 or a 4 to 7-membered non-aromatic heterocyclyl group).

Another more preferred embodiment of the ring A is represented by the formula (XIV ): (XIV ) 4b 5b (wherein each of R and R is independently a hydrogen atom or a C alkyl group, and R is a C alkyl group (the C alkyl group is unsubstituted or substituted with 1-6 1-6 one or two identical or different substituents independently selected from the group consisting of cyano groups, hydroxy groups, C alkoxy groups, C alkylthio groups, 1-3 1-3 di-C alkylamino groups, di-C alkylaminocarbonyl groups, C cycloalkyl groups, 4 to 1-3 1-3 3-6 7-membered non-aromatic heterocyclyl groups), a C haloalkyl group, a C cycloalkyl 1-6 3-6 group or a 4 to 7-membered non-aromatic heterocyclyl group).

A further preferred embodiment of the ring A is represented by the formula (XI ): (XI ) 6b 8b (wherein each of R and R is independently a hydrogen atom, a halogen atom or a C alkyl group).

Another further preferred embodiment of the ring A is represented by the formula (XII ): (XII ) (wherein R is a hydrogen atom, a halogen atom or a C alkyl group).

Another further preferred embodiment of the ring A is represented by the formula (XIII ): (XIII ) (wherein R is a hydrogen atom, a halogen atom or a C alkyl group).

Another further preferred embodiment of the ring A is represented by the formula (XIV ): (XIV ) 4b 5b 10b (wherein each of R , R and R is independently a hydrogen atom or a C alkyl group).

Another further preferred embodiment of the ring A is represented by the formula (XXIV ): (XXIV ) (wherein R is a hydrogen atom).

Another further preferred embodiment of the ring A is represented by the formula (XXIV ): (XXIV ) (wherein R is a C alkyl group (the C alkyl group is unsubstituted or substituted 1-6 1-6 with one or two identical or different substituents independently selected from the group consisting of cyano groups, hydroxy groups, C alkoxy groups, C alkylthio groups, 1-3 1-3 di-C alkylamino groups and 4 to 7-membered non-aromatic heterocyclyl groups), a C haloalkyl group, a C cycloalkyl group or a 4 to 7-membered non-aromatic 1-6 3-6 heterocyclyl group).

A particularly preferred embodiment of the ring A is represented by the formula (XI ): (XI ) 6b 8b (wherein R is a hydrogen atom, a halogen atom or a C alkyl group, and R is a hydrogen atom).

Another particularly preferred embodiment of the ring A is represented by the formula (XII ): (XII ) (wherein R is a hydrogen atom).

Another particularly preferred embodiment of the ring A is represented by the formula (XIII ): (XIII ) (wherein R is a hydrogen atom).

Another particularly preferred embodiment of the ring A is represented by the formula (XIV ): (XIV ) 4b 5b 10b (wherein each of R , R and R is a hydrogen atom).

A preferred embodiment of the substituent L is a single bond or a C alkylene group.

A further preferred embodiment of the substituent L is a single bond.

A preferred embodiment of the ring B is a C cycloalkane, a 3 to 11-membered 3-11 non-aromatic heterocycle, benzene or a 5 to 10-membered aromatic heterocycle.

A more preferred embodiment of the ring B is a C cycloalkane, a 4 to 7- membered non-aromatic heterocycle or a 5 to 6-membered aromatic heterocycle.

Another more preferred embodiment of the ring B is adamantane.

A further preferred embodiment of the ring B is a C cycloalkane or a 4 to 7- membered non-aromatic heterocycle.

A particularly preferred embodiment of the ring B is cyclohexane or piperidine.

Another preferred embodiment of the substituent L is a C alkylene group, a C 1-3 1- haloalkylene group (the C alkylene group and the C haloalkylene group are 3 1-3 1-3 unsubstituted or substituted with a hydroxy group) or a C alkenylene group (the C 2-6 2-6 alkenylene group is unsubstituted or substituted with a cyano group).

Another preferred embodiment of the substituent L is a C alkylene group (the C alkylene group is unsubstituted or substituted with one or two cyano groups) or a C haloalkylene group.

A more preferred embodiment of the substituent L is a single bond or a C alkylene group.

Another more preferred embodiment of the substituent L is a C alkylene group.(the C alkylene group is substituted with a cyano group) or a C haloalkylene 1-3 1-3 group.

Another more preferred embodiment of the substituent L is a C alkenylene group (the C alkenylene group is substituted with a cyano group).

A further preferred embodiment of the substituent L is a single bond or a methylene group. 3b 2b A preferred embodiment of the substituent L and the substituent R is such that 3b 2b L is a single bond, and R is a hydrogen atom, a halogen atom, a C cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to -membered aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11- membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 10- membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ). 3b 2b Another preferred embodiment of the substituent L and the substituent R is 3b 2b such that L is a single bond, and R is a hydrogen atom, a halogen atom, a C 3-11 cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a phenyl group, a naphthyl group, a 5 to 10-membered aromatic heterocyclyl group or a 8 to 11- membered partially saturated aromatic cyclic group (the C cycloalkyl group, the 3 to 3-11 11-membered non-aromatic heterocyclyl group, the phenyl group, the naphthyl group, the 5 to 10-membered aromatic heterocyclyl group and the 8 to 11-membered partially saturated aromatic cyclic group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V and the substituent set V ). 3b 2b Another preferred embodiment of the substituent L and the substituent R is 3b b b such that L is represented by any of the following formulae (VI -1) to (VI -11): 12b 1b 12b E E 1b b b b b b b (VI -1 ) (VI -2 ) (VI -3 ) (VI -4 ) (VI -5 ) (VI -6 ) O O (VI ) 12b 13b 12b 13b R R 12b b b b (VI -10 ) (VI -11 ) (VI -7 ) (VI -8 ) (VI -9 ) 1b 12b 13b (wherein E is an oxygen atom or a sulfur atom, and each of R and R is independently a hydrogen atom, a C alkyl group or a C haloalkyl group), and R is 1-6 1-6 a hydrogen atom, a C alkyl group (the C alkyl group is unsubstituted or substituted 1-6 1-6 with one or more identical or different substituents independently selected from the substituent set V ), a C alkenyl group, a C cycloalkyl group, a 3 to 11-membered 2-6 3-6 non-aromatic heterocyclyl group, a phenyl group or a 5 to 10-membered aromatic heterocyclyl group (the C alkenyl group, the C cycloalkyl group, the 3 to 11- 2-6 3-6 membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 10- membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ). 3b 2b Another preferred embodiment of the substituent L and the substituent R is 3b b b such that L is represented by any of the following formulae (VI -1) to (VI -11): 12b E E O O b b b b b (VI -1 ) (VI -2 ) (VI -3 ) (VI -4 ) (VI -5 ) (VI -6 ) O O (VI ) 12b 13b R 12b 13b b b b (VI -10 ) (VI -11 ) (VI -7 ) (VI -8 ) (VI -9 ) 1b 12b 13b (wherein E is an oxygen atom or a sulfur atom, and each of R and R is independently a hydrogen atom, a C alkyl group or a C haloalkyl group (the C 1-6 1-6 1-6 alkyl group and the C haloalkyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of cyano groups, hydroxy groups, C alkoxy groups, C cycloalkyl groups, 4 to 7- 1-6 3-6 membered non-aromatic heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups)), and R is a hydrogen atom, a C alkyl group, a C 1-6 2-6 alkenyl group (the C alkyl group and the C alkenyl group are unsubstituted or 1-6 2-6 substituted with one or more identical or different substituents independently selected 6b 9b from the substituent set V and the substituent set V ), a C cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a phenyl group, a 5 to 10-membered aromatic heterocyclyl group or a 8 to 11-membered partially saturated aromatic cyclic group (the C cycloalkyl group, the 3 to 11-membered non-aromatic heterocyclyl group, the phenyl group, the 5 to 10-membered aromatic heterocyclyl group and the 8 to 11- membered partially saturated aromatic cyclic group are unsubstituted or substituted with one or more identical or different substituents independently selected from the 4b 9b substituent set V and the substituent set V ). 3b 2b A more preferred embodiment of the substituent L and the substituent R is 3b 2b such that L is a single bond, and R is a hydrogen atom, a halogen atom, a C cycloalkyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ). 3b 2b Another more preferred embodiment of the substituent L and the substituent R 3b 2b is such that L is a single bond, and R is a hydrogen atom, a halogen atom, a C cycloalkyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 10-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7- membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 10- membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ). 3b 2b Another more preferred embodiment of the substituent L and the substituent R 3b 2b is such that L is a single bond, and R is a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 6- membered aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of C alkyl groups, C alkoxy groups (the C alkyl group and the C alkoxy group are 1-6 1-6 1-6 1-6 substituted with a hydroxy group or a cyano group), mono-C alkylamino groups, di-C 1-6 1- alkylamino groups, the mono-C alkylaminocarbonyl groups, the di-C 6 1-6 1-6 alkylaminocarbonyl groups, C alkylcarbonylamino groups (the mono-C alkylamino 1-6 1-6 group, the di-C alkylamino group, mono-C alkylaminocarbonyl groups, di-C 1-6 1-6 1-6 alkylaminocarbonyl groups and the C alkylcarbonylamino groups are substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms), phenyl groups, 5 to 6-membered aromatic heterocyclyl groups (the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms, cyano atoms and C haloalkyl groups)). 3b 2b Another more preferred embodiment of the substituent L and the substituent R 3b 2b is such that L is a single bond, and R is a 8 to 11-membered partially saturated aromatic cyclic group (the 8 to 11-membered partially saturated aromatic cyclic group is unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of hydroxy groups, amino groups, halogen atoms, cyano groups, nitro groups, carbamoyl groups, sulfamoyl groups, C alkyl groups, C haloalkyl groups, C alkoxy groups, C haloalkoxy groups, mono- 1-6 1-6 1-6 C alkylamino groups, di-C alkylamino groups, C alkylthio groups, C 1-6 1-6 1-6 1-6 haloalkylthio groups, C alkylcarbonyl groups, C haloalkylcarbonyl groups, C 1-6 1-6 1-6 alkylsulfonyl groups, C haloalkylsulfonyl groups and C alkoxycarbonyl groups). 1-6 1-6 3b 2b Another more preferred embodiment of the substituent L and the substituent R 3b b b is such that L is represented by any of the following formulae (XV -1) to (XV -9): b b b b (XV -5) (XV -1) ( XV -2) ( XV -3) ( XV -4) (XV ) b b b b (XV -6) ( XV -7) (XV -8) (XV -9) 12b 2b (wherein R is a hydrogen atom or a C alkyl group), and R is a hydrogen atom, a C alkyl group or a C haloalkyl group (the C alkyl group and the C haloalkyl 1-6 1-6 1-6 1-6 group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, amino groups, carbamoyl groups, sulfamoyl groups, tetrazolyl groups, cyano groups, nitro groups, C cycloalkyl groups, C alkoxy groups, C haloalkoxy groups, C alkylsulfonyl groups, 1-3 1-6 1-3 C haloalkylsulfonyl groups, 4 to 7-membered non-aromatic heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups). 3b 2b Another more preferred embodiment of the substituent L and the substituent R 3b b b is such that L is represented by any of the following formulae (XV -1) to (XV -9): O O O b b b b (XV -1) ( XV -2) ( XV -3) ( XV -4) (XV -5) (XV ) 12 b b b b b (XV -6) ( XV -7) (XV -8) (XV -9) 12b 2b (wherein R is a hydrogen atom, a C alkyl group or a C haloalkyl group), and R 1-6 1-6 is a C alkyl group (the C alkyl group is substituted with a substituent selected from 1-6 1-6 the group consisting of a C cycloalkyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group and a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group is substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, halogen atoms and cyano groups)), a C cycloalkyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6- membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, halogen atoms, cyano groups, C alkyl groups, C haloalkyl groups and C 1-3 1-3 1-6 alkoxycarbonyl groups). 3b 2b Another more preferred embodiment of the substituent L and the substituent R 3b b b is such that L is represented by any of the following formulae (XXXIV -1) to (XXXIV - (wherein R is a C alkyl group (the C alkyl group is substituted with a substituent 1-6 1-6 selected from the group consisting of a cyano group, a hydroxy group and a phenyl group)), and R is a C alkyl group (the C alkyl group is unsubstituted or substituted 1-6 1-6 with a substituent selected from the group consisting of a hydroxy group, a cyano group and a phenyl group) or a C haloalkyl group. 3b 2b 3b A further preferred embodiment of the substituent L and the R is such that L is a single bond, and R is a hydrogen atom, a phenyl group (the phenyl group is unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, cyano groups, C alkyl groups, C haloalkyl groups, C alkoxy groups and C 1-3 1-3 1-3 1-3 haloalkoxy groups). 3b 2b Another further preferred embodiment of the substituent L and the R is such 3b 2b that L is a single bond, and R is a hydrogen atom, a C cycloalkyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, cyano groups, nitro groups, C alkyl groups, C haloalkyl groups 1-3 1-3 and C alkoxycarbonyl groups). 3b 2b Another further preferred embodiment of the substituent L and the R is such 3b 2b that L is a single bond, and R is an indolinyl group. 3b 2b Another further preferred embodiment of the substituent L and the R is such 3b 2b that L is a single bond, and R is a 4 to 7-membered non-aromatic heterocyclyl group (the 4 to 7-membered non-aromatic heterocyclyl group is unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of hydroxy groups, halogen atoms, cyano groups, C alkyl groups, C 1-6 1- haloalkyl groups, C alkoxy groups, C haloalkoxy groups and C alkoxycarbonyl 6 1-6 1-6 1-6 groups). 3b 2b Another further preferred embodiment of the substituent L and the R is such 3b 2b that L is a single bond, and R is a 4 to 7-membered non-aromatic heterocyclyl group (the 4 to 7-membered non-aromatic heterocyclyl group is substituted with a C alkyl groups (the C alkyl group is substituted with a cyano group)). 3b 2b Another further preferred embodiment of the substituent L and the R is such 3b 2b that L is a single bond, and R is a 8 to 11-membered partially saturated aromatic cyclic group (the 8 to 11-membered partially saturated aromatic cyclic group is unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms). 3b 2b Another further preferred embodiment of the substituent L and the R is such 3b b b that L is represented by the following formula (VIII -1) or (VIII -2): ( VIII ) ( VIII -1) (VIII -2) 40 ,and R is a C alkyl group or a C haloalkyl group (the C alkyl group and the C 1-6 1-3 1-6 1-3 haloalkyl group are unsubstituted or substituted with a cyano group or a C cycloalkyl group). 3b 2b Another further preferred embodiment of the substituent L and the R is such 3b b b that L is represented by the following formula (VIII -1) or (VIII -2): ( VIII ) ( VIII -1) (VIII -2) , and R is a C alkyl group (the C alkyl group is substituted with a phenyl group). 1-3 1-3 3b 2b Another further preferred embodiment of the substituent L and the R is such 3b b b that L is represented by the following formula (VIII -1) or (VIII -2): ( VIII ) ( VIII -1) (VIII -2) ,and R is a C alkyl group (the C alkyl group is substituted with a phenyl group (the 1-3 1-3 phenyl group is substituted with a halogen atom)), a C cycloalkyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms, cyano groups, C alkyl groups and C 1-6 1-3 haloalkyl groups). 3b 2b Another further preferred embodiment of the substituent L and the R is such 3b b that L is represented by the formula (XXV ): ( XXV ) 12b 2b (wherein R is a hydrogen atom), and R is a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with a substituent selected from the group consisting of a C alkyl group and a C haloalkyl group). 1-3 1-3 3b 2b Another further preferred embodiment of the substituent L and the R is such 3b b that L is represented by the formula (XXVI ): ( XXVI ) , and R is a C alkyl group (the C alkyl group is unsubstituted or substituted with a 1-6 1-6 phenyl group). 3b 2b Another further preferred embodiment of the substituent L and the R is such 3b b that L is represented by the formula (XXVII ): ( XXVII ) , and R is a hydrogen atom or a C alkyl group. 3b 2b Another further preferred embodiment of the substituent L and the R is such 3b b that L is represented by the formula (XXXV ): 12b 2b (wherein R is a C haloalkyl group), and R is a C alkyl group (the C alkyl 1-3 1-6 1-6 group is unsubstituted or substituted with a cyano group) or a C haloalkyl group. 3b 2b Another further preferred embodiment of the substituent L and the R is such 3b b that L is represented by the formula (XXXII ): 12b 2b (wherein R is a hydrogen atom or a C alkyl group), and R is a hydrogen atom, a C alkyl group or a C haloalkyl group (the C alkyl group and the C haloalkyl 1-6 1-6 1-6 1-6 group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, cyano groups, C alkoxy groups, C cycloalkyl groups, 4 to 7-membered non-aromatic heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups). 3b 2b Another further preferred embodiment of the substituent L and the R is such 3b b that L is represented by the formula (XXXII ): 12b 2b (wherein R is a C haloalkyl group), and R is a hydrogen atom, a C alkyl group 1-3 1-6 or a C haloalkyl group (the C alkyl group and the C haloalkyl group are 1-6 1-6 1-6 unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, cyano groups, C alkoxy groups, C cycloalkyl groups, 4 to 7-membered non-aromatic heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups). 3b 2b Another further preferred embodiment of the substituent L and the R is such 3b b that L is represented by the formula (XXXII ): 12b 2b (wherein R is a hydrogen atom or a C alkyl group), and R is a C alkyl group 1-3 1-6 (the C alkyl group is substituted with a C cycloalkyl group (the C cycloalkyl group 1-6 3-6 3-6 is substituted with a hydroxy group)), a C cycloalkyl group, a 4 to 7-membered non- aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of C alkyl groups, C haloalkyl 1-3 1-3 groups and C alkoxycarbonyl groups). 3b 2b Another further preferred embodiment of the substituent L and the R is such 3b b that L is represented by the formula (XXXII ): (wherein R is a C alkyl group (the C alkyl group is substituted with a substituent 1-3 1-3 selected from the group consisting of a cyano group, a hydroxy group and a phenyl group)), and R is a C alkyl group (the C alkyl group is unsubstituted or substituted 1-6 1-6 with a substituent selected from the group consisting of a hydroxy group, a cyano group and a phenyl group) or a C haloalkyl group. 3b 2b A particularly preferred embodiment of the substituent L and the R is such that 3b 2b L is a single bond, and R is a hydrogrn atom or a phenyl group (the phenyl group is unsubstituted or substituted with one or more identical or different halogen atoms selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms). 3b 2b Another particularly preferred embodiment of the substituent L and the R is 3b 2b such that L is a single bond, and R is a phenyl group (the phenyl group is unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms, cyano groups and C haloalkyl groups). 3b 2b Another particularly preferred embodiment of the substituent L and the R is 3b 2b such that L is a single bond, and R is a 5 to 6-membered aromatic heterocyclyl group (the 5 to 6-membered aromatic heterocyclyl group is unsubstituted or substituted with a substituent selected from the group consisting of a halogen atom, a cyano group, a nitro group, a C alkyl group, a C haloalkyl group and a C alkoxycarbonyl group). 1-3 1-3 1-3 3b 2b Another particularly preferred embodiment of the substituent L and the R is 3b 2b such that L is a single bond, and R is a C cycloalkyl group. 3b 2b Another particularly preferred embodiment of the substituent L and the R is 3b 2b such that L is a single bond, and R is a 4 to 7-membered non-aromatic heterocyclyl group (the 4 to 7-membered non-aromatic heterocyclyl group is unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, halogen atoms, cyano groups, C alkyl groups and C haloalkyl groups). 3b 2b Another particularly preferred embodiment of the substituent L and the R is 3b b b such that L is represented by the following formula (VIII -1) or (VIII -2): ( VIII ) ( VIII -1) (VIII -2) and R is a methyl group (the methyl group is unsubstituted or substituted with a cyano group, a cyclopropyl group or a trifluoromethyl group) or an isobutyl group. 3b 2b Another particularly preferred embodiment of the substituent L and the R is 3b b b such that L is represented by the following formula (VIII -1) or (VIII -2): ( VIII ) ( VIII -1) (VIII -2) and R is a phenyl group (the phenyl group is unsubstituted or substituted with a substituent selected from the group consisting of a halogen atom, a cyano group and a C haloalkyl group) or a 5 to 6-membered aromatic heterocyclyl group (the 5 to 6- membered aromatic heterocyclyl group is unsubstituted or substituted with a halogen atom). 3b 2b Another particularly preferred embodiment of the substituent L and the R is 3b b such that L is represented by the formula (XXXII ): 12b 2b (wherein R is a hydrogen atom), and R is a C cycloalkyl group or a 4 to 7- membered non-aromatic heterocyclyl group (the C cycloalkyl group and the 4 to 7- membered non-aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of C alkyl groups, C haloalkyl groups and C alkoxycarbonyl groups). 1-3 1-3 1-6 b 3b b A preferred embodiment of n and the substituent R is such that n is 0, 1 or 2, and R is a hydroxy group, an amino group, a halogen atom, a cyano group, a C alkyl group, a C haloalkyl group, a C alkoxy group or a C haloalkoxy group (when 1-3 1-3 1-3 b 3b n is 2, R ’s may be identical or different). b 3b b A more preferred embodiment of n and the substituent R is such that n is 0 or 1, and R is a C alkyl group.

As favorable tricyclic pyridine compounds of the present invention for use as JAK inhibitors and as preventive, therapeutic and/or improving agent for diseases against which inhibition of JAK is effective, the following compound may be mentioned. 1 ) Compounds represented by the formula (I ): 1b b (R ) b ( I ) [wherein R is a hydrogen atom or a halogen atom, b 15b 15b X is a nitrogen atom or CR (wherein R is a hydrogen atom, a halogen atom, a cyano group, a C alkyl group, a C haloalkyl group or a C cycloalkyl group), 1-6 1-6 3-6 b 16b 16b Y is CR (wherein R is a hydrogen atom), the ring A is represented by the formula (II ): (II ) 1b 4b 5b 17b 1b (wherein T is CR R , C(=O), C(=S), C(=NR ), a sulfur atom, S(=O) or S(=O) , U 6b 1b 8b b is a nitrogen atom or CR , and W is a nitrogen atom or CR ), the formula (III ): (III ) 2b 4b 2b 6b 2b 8b 9b (wherein T is CR , U is a nitrogen atom or CR , and W is CR R , C(=O), C(=S), 17b 10b C(=NR ), NR , an oxygen atom, a sulfur atom, S(=O) or S(=O) (provided that when 2b 6b 2b b U is CR , W is not C(=O))) or the formula (IV ): 3b (IV ) 3b 4b 5b 17b 3b (wherein T is CR R , C(=O), C(=S), C(=NR ), a sulfur atom, S(=O) or S(=O) , U 6b 7b 17b 10b is CR R , C(=O), C(=S), C(=NR ), NR , an oxygen atom, a sulfur atom, S(=O) or 3b 8b 9b 17b 11b S(=O) , and W is CR R , C(=O), C(=S), C(=NR ), NR , an oxygen atom, a sulfur 3b 4b 5b 3b 6b 7b 3b atom, S(=O) or S(=O) (provided that when T is CR R , and U is CR R , W is 8b 9b not CR R )), L is a single bond or a C alkylene group, L is a single bond, a C alkylene group, a C alkenylene group or a C alkynylene 1-6 2-6 2-6 group (the C alkylene group, the C alkenylene group and the C alkynylene group 1-6 2-6 2-6 are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, amino groups, cyano groups and nitro groups), the ring B is a C cycloalkane, a C cycloalkene, a 3 to 11-membered non-aromatic 3-11 3-11 heterocycle, a C aromatic carbocycle or a 5 to 10-membered aromatic heterocycle, 6-14 n is 0 or 1, R is a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a tetrazolyl group, a halogen atom, a cyano group, a nitro group, a C alkyl group, a C 1-3 1-3 haloalkyl group, a C cycloalkyl group, a C alkoxy group, a C haloalkoxy group or 3-6 1-3 1-3 a C alkylsulfonyl group, and 3b b b L is a single bond or represented by any of the following formulae (XXII -1) to (XXII - ): (wherein E is an oxygen atom or a sulfur atom), 3b 2b when L is a single bond, R is a hydrogen atom, a halogen atom, a C cycloalkyl 3-11 group, a 3 to 11-membered non-aromatic heterocyclyl group, a C aryl group , a 5 to 6-14 -membered aromatic heterocyclyl group, a 8 to 11-membered partially saturated aromatic cyclic group or a 8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon group (the C cycloalkyl group, the 3 to 11-membered non-aromatic 3-11 heterocyclyl group, the C aryl group , the 5 to 10-membered aromatic heterocyclyl 6-14 group, the 8 to 11-membered partially saturated aromatic cyclic group and the 8 to 11- membered aromatic ring-condensed alicyclic hydrocarbon group are unsubstituted or substituted with one or more identical or different substituents independently selected 4b 9b from the substituent set V and the substituent set V ), 3b 2b when L is not a single bond, R is a hydrogen atom, a C alkyl group, a C alkenyl 1-6 2-6 group (the C alkyl group and the C alkenyl group are unsubstituted or substituted 1-6 2-6 with one or more identical or different substituents independently selected from the 6b 9b substituent set V and the substituent set V ), a C cycloalkyl group, a 3 to 11- 3-11 membered non-aromatic heterocyclyl group, a C aryl group , a 5 to 10-membered 6-14 aromatic heterocyclyl group, a 8 to 11-membered partially saturated aromatic cyclic group or a 8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon group (the C cycloalkyl group, the 3 to 11-membered non-aromatic heterocyclyl group, the C 3-11 6-14 aryl group , the 5 to 10-membered aromatic heterocyclyl group, the 8 to 11-membered partially saturated aromatic cyclic group and the 8 to 11-membered aromatic ring- condensed alicyclic hydrocarbon group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set 4b 9b V and the substituent set V ), n is 0, 1 or 2, R is a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a sulfamoyl group, a phosphono group, a phosphonooxy group, a sulfo group, a sulfoxy group, a tetrazolyl group, a halogen atom, a cyano group, a nitro group, a C alkyl group, a C haloalkyl group, a C cycloalkyl group, a C alkenyl group, a C 1-6 3-11 2-6 2-6 haloalkenyl group, a C alkoxy group, a C haloalkoxy group, a C alkylthio group, a 1-6 1-6 1-6 C haloalkylthio group, a C alkylcarbonyl group, a C haloalkylcarbonyl group, a C 1-6 1-6 1-6 1- alkylsulfonyl group, a C haloalkylsulfonyl group, a C alkoxycarbonyl group, a 6 1-6 1-6 mono-C alkylamino group, a di-C alkylamino group, a mono-C 1-6 1-6 1-6 alkylaminocarbonyl group, a di-C alkylaminocarbonyl group or a C 1-6 1-6 b 3b alkylcarbonylamino group (when n is 2, R ’s may be identical or different), 4b 5b 6b 7b 8b 9b each of R , R , R , R , R and R is independently a hydrogen atom, a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a tetrazolyl group, a halogen atom, a cyano group, a C alkyl group, a C alkenyl group, a C alkoxy 1-6 2-6 1-6 group, a C alkylthio group, a C alkylcarbonyl group, a C alkylsulfonyl group, a 1-6 1-6 1-6 mono-C alkylamino group, a di-C alkylamino group (the C alkyl group, the C 1-6 1-6 1-6 2-6 alkenyl group, the C alkoxy group, the C alkylthio group, the C alkylcarbonyl 1-6 1-6 1-6 group, the C alkylsulfonyl group, the mono-C alkylamino group and the di-C 1-6 1-6 1-6 alkylamino group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a C alkoxycarbonyl group, a C cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a 3-11 C aryl group or a 5 to 10-membered aromatic heterocyclyl group (the C cycloalkyl 6-14 3-11 group, the 3 to 11-membered non-aromatic heterocyclyl group, the C aryl group and 6-14 the 5 to 10-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), 10b 11b each of R and R is independently a hydrogen atom, a C alkyl group, a C 1-6 2-6 alkenyl group, a C alkylcarbonyl group, a C alkylsulfonyl group, a C 1-6 1-6 1-6 alkoxycarbonyl group, a mono-C alkylaminocarbonyl group, a di-C 1-6 1-6 alkylaminocarbonyl group (the C alkyl group, the C alkenyl group, the C 1-6 2-6 1-6 alkylcarbonyl group, the C alkylsulfonyl group, the C alkoxycarbonyl group, the 1-6 1-6 mono-C alkylaminocarbonyl group and the di-C alkylaminocarbonyl group are 1-6 1-6 unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a C cycloalkyl group, a 3 to 11- 3-11 membered non-aromatic heterocyclyl group, a C aryl group or a 5 to 10-membered 6-14 aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11-membered non- 3-11 aromatic heterocyclyl group, the C aryl group and the 5 to 10-membered aromatic 6-14 heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), 12b 13b each of R and R is independently a hydrogen atom, a C alkyl group or a C 1-6 1-6 haloalkyl group (the C alkyl group and the C haloalkyl group are unsubstituted or 1-6 1-6 substituted with one or more identical or different substituents independently selected 3b 8b 9b from the substituent set V , the substituent set V and the substituent set V ), and 40 R is a hydrogen atom, a hydroxy group, a cyano group, a nitro group, a C alkyl group or a C alkoxy group], tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b 1b 2 ) The compounds according to 1 ), wherein R is a hydrogen atom or a halogen atom, b 15b 15b X is a nitrogen atom or CR (wherein R is a hydrogen atom, a halogen atom, a 45 cyano group, a C alkyl group, a C haloalkyl group or a C cycloalkyl group), 1-6 1-6 3-6 b 16b 16b Y is CR (wherein R is a hydrogen atom), the ring A is represented by the formula (II ): (II ) 1b 4b 5b 17b 1b (wherein T is CR R , C(=O), C(=S), C(=NR ), a sulfur atom, S(=O) or S(=O) , U 6b 1b 8b b is a nitrogen atom or CR , and W is a nitrogen atom or CR ), the formula (III ): (III ) 2b 4b 2b 6b 2b 8b 9b (wherein T is CR , U is a nitrogen atom or CR , and W is CR R , C(=O), C(=S), 17b 10b C(=NR ), NR , an oxygen atom, a sulfur atom, S(=O) or S(=O) (provided that when 2b 6b 2b b U is CR , W is not C(=O))) or the formula (IV ): 3b (IV ) 3b 4b 5b 17b 3b (wherein T is CR R , C(=O), C(=S), C(=NR ), a sulfur atom, S(=O) or S(=O) , U 6b 7b 17b 10b is CR R , C(=O), C(=S), C(=NR ), NR , an oxygen atom, a sulfur atom, S(=O) or 3b 8b 9b 17b 11b S(=O) , and W is CR R , C(=O), C(=S), C(=NR ), NR , an oxygen atom, a sulfur 3b 4b 5b 3b 6b 7b 3b atom, S(=O) or S(=O) (provided that when T is CR R , and U is CR R , W is 8b 9b not CR R )), L is a single bond or a C alkylene group, L is a single bond, a C alkylene group or a C haloalkylene group (the C alkylene 1-6 1-6 1-6 group and the C haloalkylene group are unsubstituted or substituted with one or more hydroxy groups or one or more cyano groups), the ring B is a C cycloalkane, a C cycloalkene, a 3 to 11-membered non-aromatic 3-11 3-11 heterocycle, a C aromatic carbocycle or a 5 to 10-membered aromatic heterocycle, 6-14 n is 0 or 1, R is a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a tetrazolyl group, a halogen atom, a cyano group, a nitro group, a C alkyl group, a C 1-3 1-3 haloalkyl group, a C cycloalkyl group, a C alkoxy group, a C haloalkoxy group or 3-6 1-3 1-3 a C alkylsulfonyl group, 3b 2b L is a single bond, and R is a hydrogen atom, a halogen atom, a C cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6- membered aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), or 3b b b L is represented by any of the following formulae (VI -1) to (VI -11): 12b E 1b O b b b b b (VI -6 ) (VI -1 ) (VI -2 ) (VI -3 ) (VI -4 ) (VI -5 ) O O (VI ) 12b 13b R 12b 13b b b b (VI -10 ) (VI -11 ) (VI -7 ) (VI -8 ) (VI -9 ) 1b 12b 13b (wherein E is an oxygen atom, and each of R and R is independently a hydrogen atom or a C alkyl group), and R is a hydrogen atom, a C alkyl group (the C alkyl 1-6 1-6 1-6 group is unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a C cycloalkyl group, a 4 to 7- membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non- aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), 4b 5b 6b 7b 8b 9b each of R , R , R , R , R and R is independently a hydrogen atom, an amino group, a carbamoyl group, a halogen atom, a cyano group, a C alkyl group, a C 1-6 1-6 haloalkyl group, a C alkoxy group, a C haloalkoxy group, a C alkylsulfonyl group, 1-6 1-6 1-6 a C cycloalkyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), 10b 11b each of R and R is independently a hydrogen atom, a C alkyl group, a C 1-6 1-6 haloalkyl group, a C cycloalkyl group, a C alkoxy group, a C haloalkoxy group, a 3-6 1-6 1-6 C alkylsulfonyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), and R is a hydrogen atom, a hydroxy group, a cyano group, a nitro group, a C alkyl group or a C alkoxy group, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b 1b 3 ) The compounds according to 1 ) or 2 ), wherein R is a hydrogen atom, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b b 4 ) The compounds according to any one of 1 ) to 3 ), wherein X is a nitrogen atom or 15b 15b a CR (wherein R is a hydrogen atom, a halogen atom or a cyano group) or a nitrogen atom, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b b 5 ) The compounds according to any one of 1 ) to 4 ), wherein X is a nitrogen atom or 15b 15b CR (wherein R is a hydrogen atom), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b b 16b 16b 6 ) The compounds according to any one of 1 ) to 5 ), wherein Y is CR (wherein R is a hydrogen atom), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b b 7 ) The compounds according to any one of 1 ) to 6 ), wherein the ring A is represented by any of the following formulae (VII -1) to (VII -7): 8b 8b 8b N N N N N O S R b b b b ( VII -1 ) ( VII -2 ) ( VII -3 ) ( VII -4 ) 2b 9b 8b b R (VII ) b b b ( VII -5 ) ( VII -6 ) ( VII -7 ) 2b 4b 5b 6b 8b (wherein E is an oxygen atom or a sulfur atom, each of each of R , R , R , R and R is independently a hydrogen atom, an amino group, a carbamoyl group, a halogen atom, a cyano group, a C alkyl group, a C haloalkyl group, a C cycloalkyl group, a 1-6 1-6 3-6 C alkoxy group, a C haloalkoxy group, a C alkylsulfonyl group, a 4 to 7- 1-6 1-6 1-6 membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group, and R is a hydrogen atom, a C alkyl group, a C 1-6 1-6 haloalkyl group, a C cycloalkyl group, a C alkoxy group, a C haloalkoxy group, a 3-6 1-6 1-6 C alkylsulfonyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b b 8 ) The compounds according to any one of 1 ) to 6 ), wherein the ring A is represented by the formula (XXVIII ): (XXVIII ) 2b 3b (wherein each of E and E is independently, an oxygen atom or a sulfur atom, and R is a hydrogen atom, a C alkyl group (the C alkyl group is unsubstituted or 1-6 1-6 substituted with one or two identical or different substituents independently selected from the group consisting of cyano groups, hydroxy groups, C alkoxy groups, C 1-3 1-3 alkylthio groups, di-C alkylamino groups, di-C alkylaminocarbonyl groups, C 1-3 1-3 3-6 cycloalkyl groups and 4 to 7-membered non-aromatic heterocyclyl groups), a C haloalkyl group, a C cycloalkyl group or a 4 to 7-membered non-aromatic heterocyclyl group), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b b 9 ) The compounds according to any one of 1 ) to 7 ), wherein the ring A is represented by any of the following formulae (XVI -1) to (XVI -7): N N N b b b b (XVI -1) (XVI -2) (XVI -3) (XVI -4) ( XVI ) HN N b b b (XVI -5) (XVI -6) (XVI -7) (wherein R is a hydrogen atom or a methyl group), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b b ) The compounds according to any one of 1 ) to 6 ), wherein the ring A is represented by any of the following formula (XXIX -1) or (XXIX -2) (XXIX ) ( XXIX -1) ( XXIX -2) 2b 3b 6b (wherein E and E are oxygen atoms, R is a hydrogen atom, a halogen atom or a 8b 10b C alkyl group, and R and R are hydrogen atoms), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b 1b 11 ) The compounds according to any one of 1 ) to 10 ), wherein L is a single bond, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b 2b 12 ) The compounds according to any one of 1 ) to 11 ), wherein L is a single bond or a C alkylene group, a C alkenylene group (the C alkylene group and the C 1-6 1-6 1-6 1-6 alkenylene group are unsubstituted or substituted with a cyano group) or a C haloalkylene group, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b 2b 13 ) The compounds according to any one of 1 ) to 11 ), wherein L is a single bond or a C alkylene group, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b 2b 14 ) The compounds according to any one of 1 ) to 11 ), wherein L is a single bond or a methylene group, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b b ) The compounds according to any one of 1 ) to 14 ), wherein the ring B is a C cycloalkane or a 4 to 7-membered non-aromatic heterocycle, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b b 16 ) The compounds according to any one of 1 ) to 14 ), wherein the ring B is cyclohexane or piperidine, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b b 3b 17 ) The compounds according to any one of 1 ) to 16 ), wherein n is, 0 or 1, and R is a methyl group, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b 3b 18 ) The compounds according to any one of 1 ) to 17 ), wherein L is a single bond, and R is a hydrogen atom, a C cycloalkyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 10-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non-aromatic heterocyclyl group, the 3-11 phenyl group and the 5 to 10-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b 3b 19 ) The compounds according to any one of 1 ) to 17 ), wherein L is a single bond, and R is a hydrogen atom, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, halogen atoms, cyano groups, nitro groups, C alkyl groups, C alkoxy groups and 1-6 1-6 C alkoxycarbonyl groups (the C alkyl groups, the C alkoxy groups and the C 1-6 1-6 1-6 1-6 alkoxycarbonyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms and cyano groups)), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b 3b ) The compounds according to any one of 1 ) to 17 ), wherein L is a single bond, and R is a hydrogen atom or a phenyl group (the phenyl group is unsubstituted or substituted with one or two halogen atoms), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b 3b 21 ) The compounds according to any one of 1 ) to 17 ), wherein L is a single bond, and R is a C cycloalkyl group, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b 3b 22 ) The compounds according to any one of 1 ) to 17 ), wherein L is a single bond, and R is a 4 to 7-membered non-aromatic heterocyclyl group (the 4 to 7-membered non-aromatic heterocyclyl group is unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of hydroxy groups, halogen atoms, cyano groups, C alkyl groups (the C alkyl groups 1-6 1-6 are unsubstituted or substituted with a cyano group), C haloalkyl groups, C alkoxy 1-6 1-6 40 groups, C haloalkoxy groups and C alkoxycarbonyl groups), tautomers or 1-6 1-6 pharmaceutically acceptable salts of the compounds or solvates thereof. b b b 3b 23 ) The compounds according to any one of 1 ) to 17 ), wherein L is represented by any of the following formulae (XIX -1) to (XIX -7): 1b 12b (wherein E is an oxygen atom, and R is a hydrogen atom or a C alkyl group), and R is a hydrogen atom, a C alkyl group, a C haloalkyl group (the C alkyl group 1-6 1-6 1-6 and the C haloalkyl group are unsubstituted or substituted with a substituent selected from the group consisting of a cyano group, a hydroxy group, a C cycloalkyl group, a phenyl group and a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms, cyano groups, C alkoxy groups, C haloalkoxy groups, C alkylsulfonyl groups and C 1-3 1-3 1-3 haloalkylsulfonyl groups)), a C cycloalkyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the phenyl group and the 5 to 6- membered aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms, cyano groups, C alkyl groups, C haloalkyl groups, C alkoxy 1-6 1-3 1-3 groups, C haloalkoxy groups, C alkylsulfonyl groups and C haloalkylsulfonyl 1-3 1-3 1-3 groups), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b 3b 24 ) The compounds according to any one of 1 ) to 17 ), wherein L is represented by the following formula (VIII -1) or (VIII -2): ( VIII ) ( VIII -1) (VIII -2) and R is a C alkyl group (the C alkyl group is unsubstituted or substituted with a 1-6 1-6 substituent selected from the group consisting of a cyano group, a C cycloalkyl group, a phenyl group and a 5 to 6-membered aromatic heterocyclyl group (the phenyl group, the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms and cyano groups)) or a C haloalkyl group, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b 3b ) The compounds according to any one of 1 ) to 17 ), wherein L is represented by the following formula (VIII -1) or (VIII -2): ( VIII ) ( VIII -1) (VIII -2) and R is a methyl group (the methyl group is unsubstituted or substituted with a cyano groups, a cyclopropyl groups or a trifluoromethyl groups) or an isobutyl group, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b 3b 26 ) The compounds according to any one of 1 ) to 17 ), wherein L is represented by the formula (XXVI ): ( XXVI ) and R is a C alkyl group (the C alkyl group is unsubstituted or substituted with a 1-6 1-6 cyano group or a phenyl group), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b 3b 27 ) The compounds according to any one of 1 ) to 17 ), wherein L is represented by the formula (XXV ): ( XXV ) 12b 2b (wherein R is a hydrogen atom), and R is a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with a C alkyl group or a C 1-3 1-3 haloalkyl group), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b 3b 28 ) The compounds according to any one of 1 ) to 17 ), wherein L is represented by the formula (XXVII ): ( XXVII ) and R is a hydrogen atom or a C alkyl group, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b 3b 29 ) The compounds according to any one of 1 ) to 17 ), wherein L is represented by the formula (XXXII ): (wherein R is a hydrogen atom, a C alkyl group (the C alkyl group is 1-3 1-3 unsubstituted or substituted with a substituent selected from the group consisting of a cyano group, a hydroxy group, a C alkoxy group, a C cycloalkyl group and a phenyl 1-3 3-6 group) or a C haloalkyl group), and R is a hydrogen atom, a C alkyl group, a C haloalkyl group (the C alkyl group 1-3 1-3 1-3 and the C haloalkyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, cyano groups, C alkoxy groups, C cycloalkyl groups, 4 to 7-membered non- 1-3 3-6 aromatic heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups (the C cycloalkyl groups, the 4 to 7-membered non-aromatic heterocyclyl groups, the phenyl groups and the 5 to 6-membered aromatic heterocyclyl groups are unsubstituted or substituted with a substituent selected from the group consisting of a hydroxy group, a halogen atom and a cyano group)), a C cycloalkyl group or a 4 to 7-membered non-aromatic heterocyclyl group (the C cycloalkyl group and the 4 to 7-membered non-aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms, cyano groups, C alkyl groups, C 1-3 1-3 haloalkyl groups and C alkoxycarbonyl groups), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b 3b ) The compounds according to any one of 1 ) to 17 ), wherein L is represented by the formula (XXXV ): 12b 2b (wherein R is a hydrogen atom, a C alkyl group or a C haloalkyl group), and R 1-3 1-3 is a C alkyl group (the C alkyl group is unsubstituted or substituted with a cyano 1-6 1-6 group) or a C haloalkyl group, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b 15b 31 ) The compounds according to 1 ), wherein X is a nitrogen atom or CR (wherein R is a hydrogen atom or a halogen atom), b 16b 16b Y is CR (wherein R is a hydrogen atom), R is a hydrogen atom, b b b the ring A is represented by any of the following formulae (XVIII -1) to (XVIII -8): 8b 8b 8b 8b N N N N N O S R b b b b (XVIII -1 ) (XVIII -2 ) (XVIII -3 ) (XVIII -4 ) ( XVIII ) 2b 9b E 8b 5b E b b b b (XVIII -5 ) (XVIII -6 ) (XVIII -7 ) ( XVIII -8 ) 2b 3b (wherein each of E and E is independently an oxygen atom or a sulfur atom, and 4b 5b 6b 8b 9b each of R , R , R , R and R is independently a hydrogen atom or a C alkyl group, and R is a hydrogen atom, a C alkyl group (the C alkyl group is 1-6 1-6 unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of cyano groups, hydroxy groups, C alkoxy groups, di-C alkylamino groups, C cycloalkyl groups, 4 to 7-membered non- 1-3 3-6 aromatic heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups (the phenyl group and the 5 to 6-membered aromatic heterocyclyl groups are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms, C alkyl groups and C haloalkyl groups)), a C haloalkyl group, a C cycloalkyl group, a 4 to 7- 1-3 1-6 3-6 membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group), the ring B is a C cycloalkane, a 3 to 11-membered non-aromatic heterocycle, a C 3-11 6-14 aromatic carbocycle or a 5 to 10-membered aromatic heterocycle, L is a single bond or a C alkylene group, L is a single bond, a C alkylene group or a C alkenylene group (the C alkylene 1-6 2-6 1-6 group and the C alkenylene group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, amino groups, cyano groups and nitro groups), n is 0 or 1, R is a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a tetrazolyl group, a halogen atom, a cyano group, a nitro group, a C alkyl group, a C 1-3 1-3 haloalkyl group, a C cycloalkyl group, a C alkoxy group, a C haloalkoxy group or 3-6 1-3 1-3 a C alkylsulfonyl group, 3b b b L is a single bond or is represented by any of the following formulae (VI -1) to (VI -11) 12b 1b R 12b E E 1b E O O b b b b b (VI -1 ) (VI -2 ) (VI -3 ) (VI -4 ) (VI -5 ) (VI -6 ) O O (VI ) 12b 13b 12b 13b b b b (VI -10 ) (VI -11 ) (VI -7 ) (VI -8 ) (VI -9 ) 1b 12b 13b (wherein E is an oxygen atom or a sulfur atom, and each of R and R is independently a hydrogen atom, a C alkyl group or a C haloalkyl group (the C 1-6 1-6 1-6 alkyl group and the C haloalkyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of cyano groups, hydroxy groups, C alkoxy groups, C cycloalkyl groups, 4 to 7- 1-6 3-6 membered non-aromatic heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups)), and 3b 2b when L is a single bond, R is a hydrogen atom, a halogen atom, a C cycloalkyl 3-11 group, a 3 to 11-membered non-aromatic heterocyclyl group, a phenyl group, a naphthyl group, a 5 to 10-membered aromatic heterocyclyl group, a 8 to 11-membered partially saturated aromatic cyclic group or a 8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon group (the C cycloalkyl group, the 3 to 11-membered non- 3-11 aromatic heterocyclyl group, the phenyl group, the naphthyl group, the 5 to 10- membered aromatic heterocyclyl group, the 8 to 11-membered partially saturated aromatic cyclic group and the 8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V and the substituent set V ), and 3b 2b when L is not a single bond, R is a hydrogen atom, a C alkyl group, a C alkenyl 1-6 2-6 group (the C alkyl group and the C alkenyl group are unsubstituted or substituted 1-6 2-6 with one or more identical or different substituents independently selected from the 6b 9b substituent set V and the substituent set V ), a C cycloalkyl group, a 3 to 11- 3-11 membered non-aromatic heterocyclyl group, a C aryl group , a 5 to 10-membered 6-14 aromatic heterocyclyl group, a 8 to 11-membered partially saturated aromatic cyclic group or a 8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon group (the C cycloalkyl group, the 3 to 11-membered non-aromatic heterocyclyl group, the C 3-11 6-14 aryl group , the 5 to 10-membered aromatic heterocyclyl group, the 8 to 11-membered partially saturated aromatic cyclic group and the 8 to 11-membered aromatic ring- condensed alicyclic hydrocarbon group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set 4b 9b V and the substituent set V ), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b b 32 ) The compounds according to 1 ) or 31 ), wherein the ring A is represented by any of the following formulae (XXI -1) to (XXI -4): 9b 2b 8b E R 10b 10b 6b R O N b ( XXI ) 5b E b b b b (XXI -1 ) (XXI -2) (XXI -3 ) ( XXI -4 ) 2b 3b 4b 5b 8b 9b (wherein E and E are oxygen atoms, R , R , R and R are hydrogen atoms, and 6b 10b R is a hydrogen atom, a halogen atom or a C alkyl group, and R is a hydrogen atom, a C alkyl group (the C alkyl group is unsubstituted or substituted with one or 1-6 1-6 two identical or different substituents independently selected from the group consisting of cyano groups, hydroxy groups, C alkoxy groups, C alkylthio groups, di-C 1-3 1-3 1-3 alkylamino groups, di-C alkylaminocarbonyl groups, C cycloalkyl groups and 4 to 7- 1-3 3-6 membered non-aromatic heterocyclyl groups), a C haloalkyl group, a C cycloalkyl 1-6 3-6 group or a 4 to 7-membered non-aromatic heterocyclyl group), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b b 1b 33 ) The compounds according to 1 ), 31 ) or 32 ), wherein L is a single bond, L is a single bond , a C alkylene group (the C alkylene group is unsubstituted or 1-6 1-6 substituted with a hydroxy group or a cyano group) or a C haloalkylene group, the ring B is a C cycloalkane or a 4 to 7-membered non-aromatic heterocycle, n is 0 or 1, and R is a C alkyl group, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b b 3b 40 34 ) The compounds according to any one of 1 ) and 31 ) to 33 ), wherein L is a single bond, and R is a hydrogen atom, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group, a 5 to 10-membered aromatic heterocyclyl group or a 8 to 11-membered partially saturated aromatic cyclic group (the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group, the 5 to 10-membered aromatic heterocyclyl group and the 8 to 11- membered partially saturated aromatic cyclic group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of hydroxy groups, amino groups, carbamoyl groups, sulfamoyl groups, halogen atoms, cyano groups, nitro groups, C alkyl groups (the C alkyl groups are 1-6 1-6 unsubstituted or substituted with a cyano group), C haloalkyl groups, C cycloalkyl 1-6 3-11 group, C alkoxy groups, C haloalkoxy groups, C alkylthio groups, C 1-6 1-6 1-6 1-6 haloalkylthio groups, C alkylsulfonyl groups, C haloalkylsulfonyl groups, C 1-6 1-6 1-6 alkoxycarbonyl groups, 4 to 7-membered non-aromatic heterocyclyl groups, mono-C alkylamino groups, di-C alkylamino groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b b 3b ) The compounds according to any one of 1 ) and 31 ) to 33 ), wherein L is a single bond, and R is a 8 to 11-membered partially saturated aromatic cyclic group (the 8 to 11- membered partially saturated aromatic cyclic group is unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b 2b 36 ) The compounds according to 34 ) or 35 ), wherein L is a C alkylene group, and the ring B is cyclohexane or piperidine, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b b 3b 37 ) The compounds according to any one of 1 ) and 31 ) to 33 ), wherein L is represented by any of the following formulae (XIX -1) to (XIX -7): 1b 12b (wherein E is an oxygen atom, and R is a hydrogen atom, a C alkyl group (the C 1-6 1- alkyl group is unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of cyano groups, hydroxy groups, C alkoxy groups, C cycloalkyl groups and phenyl groups) or a C haloalkyl 1-3 3-6 1-6 groups), and R is a hydrogen atom, a C alkyl group, a C haloalkyl group (the C alkyl group 1-6 1-6 1-6 and the C haloalkyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of cyano groups, hydroxy groups, C cycloalkyl groups, 4 to 7-membered non-aromatic heterocyclyl groups, phenyl groups, 5 to 6-membered aromatic heterocyclyl groups and 8 to 11- membered partially saturated aromatic cyclic groups (the C cycloalkyl groups, the 4 to 7-membered non-aromatic heterocyclyl groups, the phenyl groups, the 5 to 6- membered aromatic heterocyclyl groups and the 8 to 11-membered partially saturated aromatic cyclic group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, amino groups, halogen atoms, cyano groups, C alkyl groups, C haloalkyl 1-6 1-3 groups, C alkoxy groups, C haloalkoxy groups, C alkylsulfonyl groups, C 1-3 1-3 1-3 1-3 haloalkylsulfonyl groups, 4 to 7-membered non-aromatic heterocyclyl group, phenyl groups, 5 to 6-membered aromatic heterocyclyl groups (the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the substituent set V ), mono-C alkylaminosulfonyl groups, di-C alkylaminosulfonyl groups and C 1-6 1-6 1-6 alkylsulfonylamino groups)), a C cycloalkyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group, a 5 to 6-membered aromatic heterocyclyl group or a 8 to 11-membered partially saturated aromatic cyclic group (the C cycloalkyl group, the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group, the 5 to 6- membered aromatic heterocyclyl group and the 8 to 11-membered partially saturated aromatic cyclic group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, amino groups, halogen atoms, cyano groups, C alkyl groups, C haloalkyl 1-6 1-3 groups, C alkoxy groups, C haloalkoxy groups, C alkylsulfonyl groups, C 1-3 1-3 1-3 1-3 haloalkylsulfonyl groups, 4 to 7-membered non-aromatic heterocyclyl groups, phenyl groups, 5 to 6-membered aromatic heterocyclyl groups (the phenyl groups and the 5 to 6-membered aromatic heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), mono-C alkylaminosulfonyl groups, di-C alkylaminosulfonyl groups and C 1-6 1-6 1-6 alkylsulfonylamino groups), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b b b 3b 38 ) The compounds according to any one of 1 ), 31 ) to 33 ) and 37 ), wherein L is represented by any of the following formulae (XXX -1) to (XXX -3): ( XXX ) b b b ( XXX -1) (XXX -2) (XXX -3) 1b 12b (wherein E is an oxygen atom, and R is a hydrogen atom), and R is a C alkyl group (the C alkyl group is unsubstituted or substituted with a 1-6 1-6 substituent selected from the group consisting of a cyano group, a C cycloalkyl group, a phenyl group and a 5 to 6-membered aromatic heterocyclyl group (the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group 40 consisting of halogen atoms, cyano groups, C alkyl groups and C haloalkyl groups)), 1-6 1-3 a C haloalkyl group, a C cycloalkyl group, a phenyl group or a 5 to 6-membered 1-3 3-6 aromatic heterocyclyl group (the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms, cyano groups, C alkyl groups and C haloalkyl groups), tautomers or pharmaceutically 1-3 1-3 acceptable salts of the compounds or solvates thereof. b b b b 3b 39 ) The compounds according to any one of 1 ) and 31 ) to 33 ), wherein L is represented by the formula (XXXII ): (wherein R is a hydrogen atom, a C alkyl group (the C alkyl group is 1-3 1-3 unsubstituted or substituted with a substituent selected from the group consisting of a cyano group, a hydroxy group, a C alkoxy group, a C cycloalkyl group and a phenyl 1-3 3-6 group) or a C haloalkyl group), and R is a hydrogen atom, a C alkyl group, a C haloalkyl group (the C alkyl group 1-3 1-3 1-3 and the C haloalkyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, cyano groups, C alkoxy groups, C cycloalkyl groups, 4 to 7-membered non- 1-3 3-6 aromatic heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups (the C cycloalkyl groups, the 4 to 7-membered non-aromatic heterocyclyl groups, the phenyl groups and the 5 to 6-membered aromatic heterocyclyl groups are unsubstituted or substituted with a substituent selected from the group consisting of a hydroxy group, a halogen atom, a cyano group and a C haloalkyl group)), a C cycloalkyl group or a 4 to 7-membered non-aromatic heterocyclyl group (the C cycloalkyl group and the 4 to 7-membered non-aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms, cyano groups, C alkyl groups, C haloalkyl groups and C alkoxycarbonyl groups), tautomers or 1-3 1-6 pharmaceutically acceptable salts of the compounds or solvates thereof. b b b b 3b 40 ) The compounds according to any one of 1 ) and 31 ) to 33 ), wherein L is represented by the following formula (XXXVI -1) or (XXXVI -2): (wherein R is a hydrogen atom, a C alkyl group (the C alkyl group is 1-3 1-3 unsubstituted or substituted with a substituent selected from the group consisting of a cyano group, a hydroxy group, a C alkoxy group, a C cycloalkyl group and a phenyl 1-3 3-6 group) or a C haloalkyl group), and R is a hydrogen atom, a C alkyl group, a C 1-3 1-3 1-3 haloalkyl group (the C alkyl group and the C haloalkyl group are unsubstituted or 1-3 1-3 substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, cyano groups, C alkoxy groups, C 1-3 3-6 cycloalkyl groups, 4 to 7-membered non-aromatic heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups), a C cycloalkyl group or a 4 to 7- membered non-aromatic heterocyclyl group, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. b b b 2b 41 ) The compounds according to 37 ) or 40 ), wherein L is a single bond or a C alkylene group, and the ring B is a cyclohexane or piperidine, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof. 42 ) Compounds represented by the formula (XVII ): ( XVII ) b 15b 15b wherein X is CR (wherein R is a hydrogen atom, a halogen atom or a cyano b 1b b group), and the rings A and B are any of the following combinations shown in Table 1 , tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof.

The symbols in Table 1 denote the following substituents.

HN N N N O N TABLE 1 ― ― ― ― ― ―― ― ― ― ― ―― ― ― ― ― ― ―― ― ― ― ― ― ― ― －― ― ― ― ― ｂ１ｂｂ１ｂｂ１ｂｂ１ｂＡＢＡＢＡＢＡＢ ― ― ― ― ― ―― ― ― ― ― ―― ― ― ― ― ― ―― ― ― ― ― ― ― ― －― ― ― ― ― １１１１Ａ１Ｂ１Ａ１Ｂ３Ａ１Ｂ５Ａ１Ｂ７１１１１Ａ２Ｂ１Ａ２Ｂ３Ａ２Ｂ５Ａ２Ｂ７１１１１Ａ３Ｂ１Ａ３Ｂ３Ａ３Ｂ５Ａ３Ｂ７１１１１Ａ４Ｂ１Ａ４Ｂ３Ａ４Ｂ５Ａ４Ｂ７１１１１Ａ５Ｂ１Ａ５Ｂ３Ａ５Ｂ５Ａ５Ｂ７１１１１Ａ６Ｂ１Ａ６Ｂ３Ａ６Ｂ５Ａ６Ｂ７１１１１Ａ７Ｂ１Ａ７Ｂ３Ａ７Ｂ５Ａ７Ｂ７１１１１Ａ８Ｂ１Ａ８Ｂ３Ａ８Ｂ５Ａ８Ｂ７１１１１Ａ１Ｂ２Ａ１Ｂ４Ａ１Ｂ６Ａ１Ｂ８１１１１Ａ２Ｂ２Ａ２Ｂ４Ａ２Ｂ６Ａ２Ｂ８１１１１Ａ３Ｂ２Ａ３Ｂ４Ａ３Ｂ６Ａ３Ｂ８１１１１Ａ４Ｂ２Ａ４Ｂ４Ａ４Ｂ６Ａ４Ｂ８１１１１Ａ５Ｂ２Ａ５Ｂ４Ａ５Ｂ６Ａ５Ｂ８１１１１Ａ６Ｂ２Ａ６Ｂ４Ａ６Ｂ６Ａ６Ｂ８１１１１Ａ７Ｂ２Ａ７Ｂ４Ａ７Ｂ６Ａ７Ｂ８１１１１Ａ８Ｂ２Ａ８Ｂ４Ａ８Ｂ６Ａ８Ｂ８ ― ― ― ― ― ―― ― ― ― ― ―― ― ― ― ― ― ―― ― ― ― ― ― ― ― －― ― ― ― ― 43 ) Compounds represented by the formula (XVII -1): ( XVII -1 ) b 15b 15b wherein X is CR (wherein R is a hydrogen atom, a halogen atom or a cyano b 2b b group), and the rings A and B are any of the following combinations shown in Table 2, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof.

The symbols in Table 2 denote the following substituents.

TABLE 2 ― ― ― ― ― ―― ― ― ― ― ―― ― ― ― ― ― ―― ― ― ― ― ― ― ― －― ― ― ― ― ｂ２ｂｂ２ｂｂ２ｂｂ２ｂＡＢＡＢＡＢＡＢ ― ― ― ― ― ―― ― ― ― ― ―― ― ― ― ― ― ―― ― ― ― ― ― ― ― －― ― ― ― ― ２２２２Ａ１Ｂ１Ａ１Ｂ３Ａ１Ｂ５Ａ１Ｂ７２２２２Ａ２Ｂ１Ａ２Ｂ３Ａ２Ｂ５Ａ２Ｂ７２２２２Ａ３Ｂ１Ａ３Ｂ３Ａ３Ｂ５Ａ３Ｂ７２２２２Ａ４Ｂ１Ａ４Ｂ３Ａ４Ｂ５Ａ４Ｂ７２２２２Ａ５Ｂ１Ａ５Ｂ３Ａ５Ｂ５Ａ５Ｂ７２２２２Ａ６Ｂ１Ａ６Ｂ３Ａ６Ｂ５Ａ６Ｂ７２２２２Ａ７Ｂ１Ａ７Ｂ３Ａ７Ｂ５Ａ７Ｂ７２２２２Ａ９Ｂ１Ａ９Ｂ３Ａ９Ｂ５Ａ９Ｂ７２２２２Ａ１Ｂ２Ａ１Ｂ４Ａ１Ｂ６Ａ１Ｂ８２２２２Ａ２Ｂ２Ａ２Ｂ４Ａ２Ｂ６Ａ２Ｂ８２２２２Ａ３Ｂ２Ａ３Ｂ４Ａ３Ｂ６Ａ３Ｂ８２２２２Ａ４Ｂ２Ａ４Ｂ４Ａ４Ｂ６Ａ４Ｂ８２２２２Ａ５Ｂ２Ａ５Ｂ４Ａ５Ｂ６Ａ５Ｂ８２２２２Ａ６Ｂ２Ａ６Ｂ４Ａ６Ｂ６Ａ６Ｂ８２２２２Ａ７Ｂ２Ａ７Ｂ４Ａ７Ｂ６Ａ７Ｂ８２２２２Ａ９Ｂ２Ａ９Ｂ４Ａ９Ｂ６Ａ９Ｂ８ ― ― ― ― ― ―― ― ― ― ― ―― ― ― ― ― ― ―― ― ― ― ― ― ― ― －― ― ― ― ― b b b 44 ) The compounds with the combinations of substituents as defined in 42 ) or 43 ), wherein X is converted to a nitrogen atom, tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof.

The compounds of the present invention can be synthesized by the processes mentioned later, but the production of the compounds of the present invention is not restricted to these general examples.

The compounds of the present invention can usually be purified by column chromatography, thin layer chromatography, high performance liquid chromatography (HPLC) or high performance liquid chromatography-mass spectrometry (LC-MS) and, if necessary, they may be obtained with high purity by recrystallization or washing with solvents.

In general, in the production of the compounds of the present invention, any solvents that are stable and inert under the reaction conditions and do not hinder the reactions may be used without any particular restrictions, and for example, sulfoxide solvents (such as dimethyl sulfoxide), amide solvents (such as N,N-dimethylformamide or N,N-dimethylacetamide), ether solvents (such as diethyl ether, 1,2-dimethoxyethane, tetrahydrofuran, 1,4-dioxane or cyclopentyl methyl ether), halogenated solvents (such as dichloromethane, chloroform or 1,2-dichloroethane), nitrile solvents (such as acetonitrile or propionitrile), aromatic hydrocarbon solvents (such as benzene or toluene), aliphatic hydrocarbon solvents (such as hexane or heptane), ester solvents (such as ethyl acetate), alcohol solvents (such as methanol, ethanol, 1-propanol, 2- propanol or ethylene glycol) and water may be mentioned. The reactions may be carried out in an arbitrary mixture of solvents mentioned above or in the absence of a solvent.

In general, in the production of the compounds of the present invention, the reaction temperature is chosen appropriately within the range of from -78°C to the boiling point of the solvent used for the reaction, and the production of the compounds of the present invention may be carried out at ordinary pressure or under pressure or with microwave irradiation.

As acids generally used in the production of the compounds of the present invention, for example, organic acids (such as acetic acid, trifluoroacetic acid or p- toluenesulfonic acid) and inorganic acids (such as sulfuric acid or hydrochloric acid) may be mentioned.

As bases generally used in the production of the compounds of the present invention, for example, organic metal compounds (such as n-butyllithium, s-butyllithium, lithiumdiisopropylamide or isopropylmagnesium bromide), organic bases (such as triethylamine, N,N-diisopropylethylamine or N,N-dimethylaminopyridine) and inorganic bases (such as sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide or sodium hydride) may be mentioned.

General processes for production of the compounds of the present invention are shown below, and the formulae of the intermediate and the end product in each step therein conceptually cover their protected derivatives, too. Herein, protected derivatives are defined as compounds which can be converted to the desired product, if necessary, through hydrolysis, reduction, oxidation, alkylation or the like and include compounds protected with chemically acceptable protective groups.

Protection and deprotection may be carried out by generally known protection and deprotection reactions (for example, by referring to Protective Groups in Organic Synthesis, Fourth edition, T. W. Greene, John Wiley & Sons Inc. (2006)).

Hydrolysis, reduction and oxidation may be carried out by generally known functional group conversions (for example, by referring to Comprehensive Organic Transformations, Second Edition, R.C.Larock, Wiley-VCH (1999)).

First, processes for producing the tricyclic pyrimidine compounds represented by the formula (I ) will be described.

Among the tricyclic pyrimidine compounds represented by the formula (I ), the compounds (1a)-3 can be produced, for example, through the following scheme (1a) (wherein R is a hydrogen atom or a protective group such as a Ts group, a TIPS group or a SEM group, and the other symbols are the same as defined above). 2a 2a 2a R 2a R 3a 3a 1a L 1a L a a 1a B B L O N B 3a a 3a a 2 3a a (R ) (R ) n n (R ) a a N (1a ) 1a 1a R N R N N PR PR (1a)-1 (1a)-2 (1a)-3 A compound (1a)-1 can be converted to a compound (1a)-2 by using an equivalent or excessive amount of hydrazine or its equivalent in an appropriate solvent or in the absence of solvent at room temperature to a refluxing temperature.

A compound (1a)-2 can be converted to a compound (1a)-3 by using an equivalent or excessive amount of an oxidizing agent such as manganese dioxide or iodobenzenediacetate in an appropriate solvent or in the absence of solvent at room temperature to a refluxing temperature. The presence of an acid or a base is sometimes effective for smooth progress of the reaction.

A compound (1a)-3 can also be obtained by using a compound (1a)-1 and an 40 equivalent or excessive amount of tosylhydrazine or its equivalent in an appropriate solvent or in the absence of solvent at room temperature to a refluxing temperature.

The presence of a base is sometimes effective for smooth progress of the reaction.

A compound (1a)-3 having a protective group as R can be converted to a compound (1a)-3 having a hydrogen atom as R by deprotection.

Among the compounds represented by the formula (I ), the compounds (2a)-2, (2a)-3 and (2a)-4 can be produced, for example, through the following scheme (2a) 2a PR (wherein E is an oxygen atom or a sulfur atom, R is a hydrogen atom or a protective group such as a Ts group, a TIPS group or a SEM group, and the other symbols are the same as defined above). 2a R L 1a 1a a 3a a 3a a (R ) (R ) 1a 1a R N R N PR PR (2a)-1 (2a)-2 (2a ) 2a R 3a L 1a R 3a a 3a a (R ) n (R ) 2a n N 1a (2a)-4 (2a)-3 A compound (2a)-1 can be converted to a compound (2a)-2 by using an 4a 4a Q 4a Q 4a Q equivalent or excessive amount of R CHO, R CO R , R C(OR ) , R CONR or 2 3 2 4a Q Q Q R C(OR ) NR (wherein R is a hydrogen atom or a C alkyl group) in an 2 2 1-6 appropriate solvent or in the absence of solvent at room temperature to a refluxing temperature. Microwave irradiation or the presence of an acid or a base is sometimes effective for smooth progress of the reaction.

A compound (2a)-1 can be converted to a compound (2a)-3 by using an equivalent or excessive amount of phosgene, phosgene dimer, phosgene trimer, 1,1’- carbonyldiimidazole, dimethyl carbonate, carbon disulfide or 1,1’- thiocarbonyldiimidazole in an appropriate solvent or in the absence of solvent at room temperature to a refluxing temperature. The presence of an acid or a base is sometimes effective for smooth progress of the reaction.

A compound (2a)-3 can be converted to a compound (2a)-4 by using equivalent or 6a L L excessive amounts of R -R (wherein R is a leaving group such as a halogen atom, a methanesulfonyloxy group or a p-toluenesulfonyloxy group) and a base such as potassium carbonate or sodium hydride in an appropriate solvent or in the absence of solvent at room temperature to a refluxing temperature.

A compound (2a)-3 or (2a)-4 having an oxygen atom as E can be converted to a compound (2a)-3 or (2a)-4 having a sulfur atom as E by using an equivalent or excessive amount of a thiocarbonylation reagent such as phosphorus pentasulfide or Lawesson's reagent in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature.

Compounds (2a)-2, (2a)-3 and (2a)-4 having a protective group as R can be converted to compounds (2a)-2, (2a)-3 and (2a)-4 having a hydrogen atom as R by deprotection.

(Synthesis of starting materials 1a) The compounds (3a)-3 and (3a)-6 can be produced, for example, through the following scheme (3a) (wherein X is a chlorine atom, a bromine atom or an iodine atom, X Y PR each of R and R is independently a C alkyl group, and R is a hydrogen atom or a protective group such as a Ts group, a TIPS group or a SEM group, and the other symbols are the same as defined above).

A compound (3a)-1 can be converted to a compound (3a)-3 by a metal-halogen exchange reaction using an equivalent or excessive amount of an organic metal reagent such as isopropylmagnesium chloride, 2,6-dimethylphenylmagnesium bromide or n- butyllithium in an appropriate solvent at -78°C to room temperature followed by treatment with an equivalent or excessive amount of a compound (3a)-2 in an appropriate solvent at -78°C to room temperature.

A compound (3a)-1 can be converted to a compound (3a)-5 by a metal-halogen exchange reaction using an equivalent or excessive amount of an organic metal reagent such as isopropylmagnesium chloride, 2,6-dimethylphenylmagnesium bromide or n- butyllithium in an appropriate solvent at -78°C to room temperature followed by treatment with an equivalent or excessive amount of a compound (3a)-4 in an appropriate solvent at -78°C to room temperature.

A compound (3a)-5 can be converted to a compound (3a)-3 by using an equivalent or excessive amount of an oxidizing agent such as manganese dioxide or 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one (Dess-Martin reagent) in an appropriate solvent at -78°C to a refluxing temperature.

A compound (3a)-3 can be converted to a compound (3a)-6 by using equivalent or excessive amounts of an amine reagent such as ammonium acetate or hydroxylamine and a reducing agent such as sodium triacetoxyborohydride or zinc in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature.

A compound (3a)-5 can be converted to a compound (3a)-6 by carrying out a reaction using equivalent or excessive amounts of phthalimide, a Mitsunobu reagent and a phosphine reagent in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature, followed by deprotection. As a Mitsunobu reagent, diethyl azodicarboxylate, diisopropyl azodicarboxylate or the like may be mentioned, and as a phosphine reagent, triphenylphosphine, tributylphosphine or the like may be mentioned.

A compound (3a)-1 having a chlorine atom as X can be converted to a compound (3a)-1 having a bromine or iodine atom as X by using an equivalent or excessive amount of hydrobromic acid or hydroiodic acid in an appropriate solvent or in the absence of solvent at 0°C to a refluxing temperature.

Compounds (3a)-3 and (3a)-6 having a protective group as R can be converted to compounds (3a)-3 and (3a)-6 having a hydrogen atom as R by deprotection.

(Synthesis of starting materials 2a) The compounds (4a)-2 can be produced, for example, through the following scheme (4a) (wherein each of R and R is independently a C alkyl group, and the other symbols are the same as defined above).

A compound (4a)-1 can be converted to a compound (4a)-2 by using equivalent or excessive amounts of R NH(OR ) and a condensation agent such as dicyclohexylcarbodiimide or 1-ethyl(3-dimethylaminopropyl)carbodiimide hydrochloride in an appropriate solvent or in the absence of solvent at 0°C to a refluxing temperature. The presence of an acid or a base is sometimes effective for smooth progress of the reaction.

Among the compounds represented by the formula (I ), the compounds (5a)-3, (5a)-4, (5a)-5 and (5a)-6 can be produced , for example, through the following scheme (5a) (wherein m is 0,1,2 or 3, R is a hydrogen atom or a protective group such as a Ts group, a TIPS group or a SEM group, R is a protective group such as a Boc group or a Cbz group, E is an oxygen atom or a sulfur atom, and the other symbols are the same as defined above). 3a a 3a a (R ) 3a a (R ) n (R ) n 2a n 3a ( ) N m ( ) N 1a R N N R PR (5a)-1 (5a)-2 2a 2a 3a (5a)-3 R N C E (5a ) (5a)-8 (5a)-7 3a a 3a a 3a a (R ) (R ) (R ) n 2a n 2a n 2a HN R R R N N N N N N ( ) ( ) ( ) E OH m m m N N N a a a X X X N N N a a a Y Y Y 1a 1a 1a N N N R N R N R N PR PR PR R R R (5a)-4 (5a)-5 (5a)-6 A compound (5a)-1 among the compounds (1a)-3 can be converted to a compound (5a)-2 by deprotection.

A compound (5a)-2 can be converted to a compound (5a)-3 by using equivalent or 2a 3a 2a L L excessive amounts of an electrophilic reagent represented by R L L -R (wherein R is a leaving group such as a halogen atom, a methanesulfonyloxy group, a p- toluenesulfonyloxy group) such as an alkyl halide, a methanesulfonate ester, an acid halide, a sulfonyl chloride, a chloroformate and a base such as triethylamine in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature.

A compound (5a)-2 can be converted to a compound (5a)-3 by using equivalent or excessive amounts of R -CHO and a reducing agent such as 2-picoline borane or sodium triacetoxyborohydride in an appropriate solvent or in the absence of solvent at room temperature to a refluxing temperature.

A compound (5a)-2 can be converted to a compound (5a)-4 by using equivalent or excessive amounts of a compound (5a)-7 and a base such as potassium carbonate or triethylamine in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature.

A compound (5a)-2 can be converted to a compound (5a)-5 or / and (5a)-6 by using equivalent or excessive amounts of a compound (5a)-8, a base such as triethylamine and an acid catalyst such as ytterbium (III) trifluoromethanesulfonate in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature.

Compounds (5a)-3, (5a)-4, (5a)-5 and (5a)-6 having a protective group as R can be converted to compounds (5a)-3, (5a)-4, (5a)-5 and (5a)-6 having a hydrogen atom as R by deprotection.

Among the compounds represented by the formula (I ), the compounds (6a)-3, (6a)-4 and (6a)-5 can be produced, for example, through the following scheme (6a) (wherein m is 0,1,2 or 3, R is a hydrogen atom or a protective group such as a Ts group, a TIPS group or a SEM group, R is a protective group such as a benzyl group or an acetyl group, and the other symbols are the same as defined above). 2a 12a 3a a 3a a 3a a R R 3a a (R ) (R ) (R ) (R ) n n 2a OR O OH N (6a)-6 ( ) N ( ) N m ( ) m ( ) a N a N (6a) 1a 1a N 1a N 1a R N R N R N R N PR PR PR PR (6a)-1 (6a)-2 (6a)-3 (6a)-4 3a a (R ) (6a)-5 A compound (6a)-1 among the compounds (1a)-3 is converted to a compound (6a)-2 by deprotection.

A compound (6a)-2 can be converted to a compound (6a)-3 by using an equivalent or excessive amount of an oxidizing agent such as 2-iodoxybenzoic acid or pyridinium chlorochromate in an appropriate solvent or in the absence of solvent at - 78°C to a refluxing temperature.

A compound (6a)-3 can be converted to a compound (6a)-4 by using equivalent or excessive amounts of a compound (6a)-6 and a reducing agent such as 2-picoline borane or sodium triacetoxyborohydride in an appropriate solvent or in the absence of solvent at room temperature to a refluxing temperature.

A compound (6a)-2 can be converted to a compound (6a)-5 by using equivalent or excessive amounts of an acidic alcohol represented by R -OH such as phenol, a Mitsunobu reagent and a phosphine reagent in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature. As a Mitsunobu reagent, diethyl azodicarboxylate, diisopropyl azodicarboxylate or the like may be mentioned, and as a phosphine reagent, triphenylphosphine, tributylphosphine or the like may be mentioned.

Compounds (6a)-3, (6a)-4 and (6a)-5 having a protective group as R can be converted to compounds (6a)-3, (6a)-4 and (6a)-5 having a hydrogen atom as R by deprotection.

Among the compounds represented by the formula (I ), the compounds (7a)-3, (7a)-4, (7a)-5, (7a)-6, (7a)-7, (7a)-8 and (7a)-9 can be produced, for example, through the following scheme (7a) (wherein m is 0,1,2 or 3, R is a hydrogen atom or a protective group such as a Ts group, a TIPS group or a SEM group, R is a protective group such as a benzyl group or an acetyl group, R is a hydrogen atom or a C alkyl group, X is a halogen atom, and the other symbols are the same as defined above).

A compound (7a)-1 among the compounds (1a)-3 can be converted to a compound (7a)-2 by deprotection.

A compound (7a)-2 can be converted to a compound (7a)-3 by using an equivalent or excessive amount of an oxidizing agent such as 2-iodoxybenzoic acid or pyridinium chlorochromate in an appropriate solvent or in the absence of solvent at - 78°C to a refluxing temperature.

A compound (7a)-3 can be converted to a compound (7a)-4 by using equivalent or excessive amounts of a compound (7a)-10 and a reducing agent such as 2-picoline borane or sodium triacetoxyborohydride in an appropriate solvent or in the absence of solvent at room temperature to a refluxing temperature.

A compound (7a)-5 can be converted to a compound (7a)-4 by using an equivalent or excessive amount of a compound (7a)-10 in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature. The presence of a base is sometimes effective for smooth progress of the reaction.

A compound (7a)-2 can be converted to a compound (7a)-5 by using equivalent or excessive amounts of a halogenating agent and a phosphine reagent in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature. As a halogenating agent, N-bromosuccinimide, N,N-diethylaminosulfur trifluoride or the like may be mentioned, and as a phosphine reagent, triphenylphosphine, tributylphosphine or the like may be mentioned.

A compound (7a)-5 can be converted to a compound (7a)-6 by using an equivalent or excessive amount of a compound (7a)-11 in an appropriate solvent or in the absence of solvent at room temperature to a refluxing temperature. The presence of an acid or a base is sometimes effective for smooth progress of the reaction.

A compound (7a)-2 can be converted to a compound (7a)-7 by using equivalent or 2a L L excessive amounts of an electrophilic reagent represented by R -R (R is a leaving group such as a halogen atom, a methanesulfonyloxy group or a p-toluenesulfonyloxy group) such as an alkyl halide, a methanesulfonyl ester or an acid halide and a base such as potassium carbonate or sodium hydroxide in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature.

A compound (7a)-2 can be converted to a compound (7a)-7 by using equivalent or excessive amounts of an acidic alcohol represented by R -OH such as phenol, a Mitsunobu reagent and a phosphine reagent in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature. As a Mitsunobu reagent, diethyl azodicarboxylate, diisopropyl azodicarboxylate or the like may be mentioned, and as a phosphine reagent, triphenylphosphine, tributylphosphine or the like may be mentioned.

A compound (7a)-2 can be converted to a compound (7a)-8 or (7a)-9 by using 2a 2a equivalent or excessive amounts of R C(=O)OH or R (C=O)SH, a Mitsunobu reagent and a phosphine reagent in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature. As R C(=O)OH, acetic acid or the like may be mentioned, as R (C=O)SH, thioacetic acid or the like may be mentioned. As a Mitsunobu reagent, diethyl azodicarboxylate, diisopropyl azodicarboxylate or the like may be mentioned, and as a phosphine reagent, triphenylphosphine, tributylphosphine or the like may be mentioned.

Compounds (7a)-3, (7a)-4, (7a)-5, (7a)-6, (7a)-7, (7a)-8 and (7a)-9 having a protective group as R can be converted to compounds (7a)-3, (7a)-4, (7a)-5, (7a)-6, (7a)-7, (7a)-8 and (7a)-9 having a hydrogen atom as R by deprotection.

Among the compounds represented by the formula (I ), the compounds (8a)-2 and (8a)-3 can be produced, for example, through the following scheme (8a) (wherein m is 0, 1, 2 or 3, R is a hydrogen atom or a protective group such as a Ts group, a TIPS group or a SEM group, and the other symbols are the same as defined above).

A compound (8a)-1 among the compounds (7a)-2 can be converted to a compound (8a)-2 by using an equivalent or excessive amount of an oxidizing agent such as Jones reagent in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature.

A compound (8a)-2 can be converted to a compound (8a)-3 by using equivalent or excessive amounts of a compound (8a)-4 and a condensation agent such as N,N’- dicyclohexylcarbodiimide or 1-ethyl(3-dimethylaminopropyl)carbodiimide hydrochloride in an appropriate solvent or in the absence of solvent at 0°C to a refluxing temperature. The presence of an acid or a base is sometimes effective for smooth progress of the reaction.

Compounds (8a)-2 and (8a)-3 having a protective group as R can be converted to compounds (8a)-2 and (8a)-3 having a hydrogen atom as R by deprotection.

Among the compounds represented by the formula (I ), the compounds (9a)-2 and (9a)-3 can be produced, for example, through the following scheme (9a) (wherein m is 0, 1, 2 or 3, R is a hydrogen atom or a protective group such as a Ts group, a TIPS 40 group or a SEM group, R is a hydrogen atom or a C alkyl group, and the other symbols are the same as defined above).

A compound (9a)-1 among the compounds (7a)-9 can be converted to a compound (9a)-2 by using an equivalent or excessive amount of an oxidizing agent such as hydrogen peroxide in an appropriate solvent or in the absence of solvent at - 78°C to a refluxing temperature. The presence of an acid catalyst such as ammonium molybdate tetrahydrate is sometimes effective for smooth progress of the reaction.

A compound (9a)-2 can be converted to a compound (9a)-3 by using equivalent or excessive amounts of a compound (9a)-4 and a halogenating agent such as thionyl chloride or phosphorus oxychloride in an appropriate solvent or in the absence of solvent at 0°C to a refluxing temperature. The presence of a base such as triethylamine is sometimes effective for smooth progress of the reaction.

Compounds (9a)-2 and (9a)-3 having a protective group as R can be converted to compounds (9a)-2 and (9a)-3 having a hydrogen atom as R by deprotection.

Among the compounds represented by the formula (I ), the compounds (10a)-2 and (10a)-3 can be produced, for example, through the following scheme (10a) (wherein m is 0, 1, 2 or 3, R is a hydrogen atom or a protective group such as a Ts group, a TIPS group or a SEM group, R is a hydrogen atom or a C alkyl group, and the other symbols are the same as defined above).

A compound (10a)-1 among the compounds (7a)-4 can be converted to a compound (10a)-2 by using an equivalent or excessive amount of an acid halide in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature.

A compound (10a)-1 among the compounds (7a)-4 can be converted to a compound (10a)-3 by using an equivalent or excessive amount of a sulfonyl halide in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature.

Compounds (10a)-2 and (10a)-3 having a protective group as R can be converted to compounds (10a)-2 and (10a)-3 having a hydrogen atom as R by deprotection.

Among the compounds represented by the formula (I ), the compounds (11a)-2, (11a)-3, (11a)-4, (11a)-5, (11a)-6, (11a)-7, (11a)-8 and (11a)-9 can be produced, for example, through the following scheme (11a) (wherein m is 0, 1, 2 or 3, R is a hydrogen atom or a protective group such as a Ts group, a TIPS group or a SEM group, Z Z1 R is a hydrogen atom or a C alkyl group, R is a C alkyl group, and the other 1-6 1-6 symbols are the same as defined above).

A compound (11a)-1 can be converted to a compound (11a)-2, (11a)-3 or (11a)-4 by using an equivalent or excessive amounts of a phosphonium ylide such as a Horner- Wadsworth-Emmons reagent and a base such as sodium hydride in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature.

A compound (11a)-2, (11a)-4 or (11a)-3 can be converted to a compound (11a)-5, (11a)-6 or (11a)-7 respectively by using an equivalent or excessive amount of a metal catalyst such as palladium-carbon catalyst under a hydrogen atmosphere in an appropriate solvent at -78°C to a refluxing temperature.

A compounds (11a)-7 can be converted to a compounds (11a)-8 by deprotection.

A compound (11a)-8 can be converted to a compound (11a)-9 by using equivalent or excessive amounts of a compound (11a)-10 and a condensation agent such as N,N’- dicyclohexylcarbodiimide or 1-ethyl(3-dimethylaminopropyl)carbodiimide hydrochloride in an appropriate solvent or in the absence of solvent at 0°C to a refluxing temperature. The presence of an acid or a base is sometimes effective for smooth progress of the reaction.

Compounds (11a)-2, (11a)-3, (11a)-4, (11a)-5, (11a)-6, (11a)-7, (11a)-8 and (11a)-9 having a protective group as R can be converted to compounds (11a)-2, (11a)-3, (11a)-4, (11a)-5, (11a)-6, (11a)-7, (11a)-8 and (11a)-9 having a hydrogen atom as R by deprotection.

Among the compounds represented by the formula (I ), the compounds (12a)-2, (12a)-3, (12a)-4 and (12a)-5 can be produced, for example, through the following scheme (12a) (wherein m is 0, 1, 2 or 3, R is a hydrogen atom or a protective group such as a Ts group, a TIPS group or a SEM group, R is a hydrogen atom or a C alkyl group, and the other symbols are the same as defined above).

A compound (12a)-1 among the compounds (7a)-3 can be converted to a compound (12a)-2 by using equivalent or excessive amounts of a phosphonium ylide such as a Horner-Wadsworth-Emmons reagent and a base such as sodium hydride in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature.

A compound (12a)-2 can be converted to a compound (12a)-3 by using an equivalent or excessive amount of a metal catalyst such as palladium-carbon catalyst under a hydrogen atmosphere in an appropriate solvent at -78°C to a refluxing temperature.

A compound (12a)-1 can be converted to a compound (12a)-4 by using equivalent or excessive amounts of malononitrile and a base such as piperidine in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature.

A compound (12a)-4 can be converted to a compound (12a)-5 by using an equivalent or excessive amount of a metal catalyst such as palladium-carbon catalyst under a hydrogen atmosphere in an appropriate solvent at -78°C to a refluxing temperature.

Compounds (12a)-2, (12a)-3, (12a)-4 and (12a)-5 having a protective group as R can be converted to compounds (12a)-2, (12a)-3, (12a)-4 and (12a)-5 having a hydrogen atom as R by deprotection.

Next, processes for producing the tricyclic pyridine compounds represented by the formula (I ) will be described.

Among the tricyclic pyridine compounds represented by the formula (I ), the compounds (1b)-2 can be produced, for example, through the following scheme (1b) (wherein R is a hydrogen atom or a protective group such as a Ts group, a TIPS group or a SEM group, and the other symbols are the same as defined above).

A compound (1b)-2 can be obtained by cyclization of a compound (1b)-1.

A compound (1b)-1 can be converted to a compound (1b)-2 by using an 8b 9b 8b Q 9b Q equivalent or excessive amount of R C(=O)R or R C(OR ) R (wherein R is a hydrogen atom or a C alkyl group) in an appropriate solvent or in the absence of solvent at room temperature to a refluxing temperature. Microwave irradiation or the presence of an acid catalyst such as acetic acid, trifluoroacetic acid, hydrochloric acid, sulfuric acid or p-toluenesulfonic acid is sometimes effective for smooth progress of the reaction.

A compound (1b)-2 having a protective group as R can be converted to a compound having a hydrogen atom as R by deprotection.

Among the compounds represented by the formula (I ), the compounds (2b)-2 and (3b)-2 can be produced, for example, through the following schemes (2b) and (3b) A PR (wherein Y is an oxygen atom or a sulfur atom, R is a hydrogen atom or a protective group such as a Ts group, a TIPS group or a SEM group, and the other symbols are the same as defined above).

A compound (2b)-2 can be obtained by cyclization of a compound (2b)-1.

A compound (2b)-1 can be converted to a compound (2b)-2 by using an 8b 8b Q 8b Q 8b Q equivalent or excessive amount of R CHO, R CO R , R C(OR ) , R CONR or 2 3 2 8b Q Q Q R C(OR ) NR (wherein R is a hydrogen atom or a C alkyl group) in an 2 2 1-6 appropriate solvent or in the absence of solvent at room temperature to a refluxing temperature. Microwave irradiation or the presence of an acid or a base is sometimes effective for smooth progress of the reaction.

A compound (2b)-2 having an oxygen atom as Y can be converted to a compound (2b)-2 having a sulfur atom as Y by using an equivalent or excessive amount of a thiocarbonylation agent such as phosphorus pentasulfide or Lawesson's reagent in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature.

A compound (2b)-2 having a protective group as R can be converted to a compound having a hydrogen atom as R by deprotection.

A compound (3b)-2 can be obtained by cyclization of a compound (3b)-1 like the synthesis of a compound (2b)-2.

A compound (3b)-2 having a protective group as R can be converted to a compound having a hydrogen atom as R by deprotection.

Among the compounds represented by the formula (I ), the compounds (4b)-2, (4b)-3 and (4b)-4 can be produced, for example, through the following scheme (4b) A PR (wherein Y is an oxygen atom or a sulfur atom, R is a hydrogen atom or a protective group such as a Ts group, a TIPS group or a SEM group, and the other symbols are the same as defined above).

A compound (4b)-2 can be obtained by cyclization of a compound (4b)-1.

A compound (4b)-1 can be converted to a compound (4b)-2 by using an equivalent or excessive amount of phosgene, phosgene dimmer, phosgene trimer, 1,1’- carbonyldiimidazole, dimethyl carbonate, 1,1’-thiocarbonyldiimidazole, carbon disulfide or the like in an appropriate solvent at room temperature to a refluxing temperature.

The presence of an acid or a base is sometimes effective for smooth progress of the reaction. 5b 10b A compound (4b)-2 having hydrogen atoms as R and R can be converted to a compound (4b)-3 by using a catalyst such as palladium-carbon or manganese dioxide in an appropriate solvent at room temperature to a refluxing temperature.

A compound (4b)-2 or (4b)-3 having an oxygen atom as Y can be converted to a compound (4b)-2 or (4b)-3 having a sulfur atom as Y by using a thiocarbonylation agent such as phosphorus pentasulfide or Lawesson's reagent in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature.

A compound (4b)-2 or (4b)-3 having a protective group as R can be converted to a compound having a hydrogen atom as R by deprotection.

A compound (4b)-1 having a hydrogen atom as R can be converted to a compound (4b)-4 by cyclization.

A compound (4b)-1 can be converted to a compound (4b)-4 by using an 8b 8b Q 8b Q 8b Q equivalent or excessive amount of R CHO, R CO R , R C(OR ) , R CONR or 2 3 2 8b Q Q Q R C(OR ) NR (wherein R is a hydrogen atom or C alkyl group) in an appropriate 2 2 1-6 solvent or in the absence of solvent at room temperature to a refluxing temperature.

Microwave irradiation or the presence of an acid or a base is sometimes effective for smooth progress of the reaction.

A compound (4b)-4 having a protective group as R can be converted to a compound having a hydrogen atom as R by deprotection.

Among the compounds represented by the formula (I ), the compounds (5b)-2 can be produced, for example, through the following scheme (5b) (wherein Y is an oxygen atom or a sulfur atom, R is a hydrogen atom or a protective group such as a Ts group, a TIPS group or a SEM group, and the other symbols are the same as defined above).

A compound (5b)-2 can be obtained by cyclization of a compound (5b)-1.

A compound (5b)-1 can be converted to a compound (5b)-2 by using an 8b 8b Q 8b Q 8b Q equivalent or excessive amount of R CHO, R CO R , R C(OR ) , R CONR or 2 3 2 8b Q Q Q R C(OR ) NR (wherein R is a hydrogen atom or a C alkyl group) in an 2 2 1-6 appropriate solvent or in the absence of solvent at room temperature to a refluxing temperature. Microwave irradiation or the presence of an acid or a base is sometimes effective for smooth progress of the reaction.

A compound (5b)-2 having an oxygen atom as Y can be converted to a compound having a sulfur atom as Y by using an equivalent or excessive amount of a thiocarbonylation agent such as phosphorus pentasulfide or Lawesson's reagent in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature.

A compound (5b)-2 having a protective group as R can be converted to a compound having a hydrogen atom as R by deprotection.

Among the compounds represented by the formula (I ), the compounds (6b)-2 and (6b)-3 can be produced, for example, through the following scheme (6b) (wherein X is a bromine atom or an iodine atom, R is a hydrogen atom or a protective group such as a Ts group, a TIPS group or a SEM group, and the other symbols are the same as defined above).

A compound (6b)-3 can be obtained by bromination or iodination of a compound (6b)-1 followed by cyanization of the resulting compound (6b)-2.

A compound (6b)-1 can be converted to a compound (6b)-2 by using an equivalent or excessive amount of a halogenating agent such as bromine, iodine, N- bromosuccinimide or N-iodosuccinimide in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature.

A compound (6b)-2 can be converted to a compound (6b)-3 by using an equivalent or excessive amount of a metal cyanide such as copper cyanide or zinc cyanide in the presence of a palladium catalyst such as tetrakis(triphenylphosphine)palladium(0) or bis(triphenylphosphine)palladium(II) dichloride in an appropriate solvent or in the absence of solvent at room temperature to a refluxing temperature.

A compound (6b)-2 or (6b)-3 having a protective group as R can be converted to a compound having a hydrogen atom as R by deprotection.

(Synthesis of starting materials 1b) The compounds (7b)-2 can be produced, for example, through the following scheme (7b) (wherein R is a leaving group such as a chlorine atom, a methanesulfonyloxy group or a p-toluenesulfonyloxy group, R is a hydrogen atom or a protective group such as a Ts group, a TIPS group or a SEM group, and the other symbols are the same as defined above).

A compound (7b)-2 can be obtained by a Mitsunobu reaction of a compound (7b)- 10b PR1 PR1 1 with R R NH (wherein R is a protective group suited for a Mitsunobu reaction such as a methanesulfonyl group or a p-toluenesulfonyl group) following by deprotection.

A compound (7b)-1 can be converted to a compound (7b)-2 by using equivalent or 10b PR1 excessive amounts of R R NH, a Mitsunobu reagent and a phosphine reagent in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature, followed by deprotection. As a Mitsunobu reagent, diethyl azodicarboxylate, diisopropyl azodicarboxylate or the like may be mentioned, and as a phosphine reagent, triphenylphosphine, tributylphosphine or the like may be mentioned. A compound (7b)- 2 having a hydrogen atom as R can be obtained by a similar reaction using 10b PR1 phthalimide instead of R R NH followed by deprotection.

A compound (7b)-2 can be obtained by conversion of a compound (7b)-1 to a compound (7b)-3 having a leaving group R followed by a substitution reaction using R NH .

A compound (7b)-1 can be converted to a compound (7b)-3 by using an equivalent or excessive amount of phosphorus oxychloride, thionyl chloride, methanesulfonyl chloride, p-toluenesulfonyl chloride or the like in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature. The presence of a base is sometimes effective for smooth progress of the reaction.

A compound (7b)-3 can be converted to a compound (7b)-2 by using an equivalent or excessive amount of R NH in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature. Microwave irradiation or the presence of a base is sometimes effective for smooth progress of the reaction.

(Synthesis of starting materials 2b) The compounds (8b)-3 can be produced, for example, through the following scheme (8b) (wherein R is a hydrogen atom or a protective group such as a Ts group, a TIPS group or a SEM group, and the other symbols are the same as defined above).

A compound (8b)-3 can be obtained by oxidation of a compound (8b)-1 followed by condensation of the resulting compound (8b)-2.

A compound (8b)-1 can be converted to a compound (8b)-2 by using an equivalent or excessive amount of a oxidizing agent such as potassium permanganate or sodium chlorite in an appropriate solvent or in the absence of solvent at room temperature to a refluxing temperature.

A compound (8b)-2 can be converted to a compound (8b)-3 by using equivalent or excessive amounts of ammonia-methanol or its equivalent and a condensation agent such as N,N’-dicyclohexylcarbodiimide or 1-ethyl(3- dimethylaminopropyl)carbodiimide hydrochloride in an appropriate solvent or in the absence of solvent at 0°C to a refluxing temperature. The presence of a catalyst such as N-hydroxybenzotriazole or a base is sometimes effective for smooth progress of the reaction.

(Synthesis of staring materials 3b) The compounds (9b)-2 and (9b)-3 can be produced, for example, through the following scheme (9b) (wherein R is a hydrogen atom or a protective group such as a Ts group, a TIPS group or a SEM group, and the other symbols are the same as defined above). 5b B 3b b (R ) 2b 1b L PR O HN 3b b (9b)-2 (R ) ( 9b) 1b 2b PR L 10b 1b NH HN 3b b (R ) (9b)-1 (9b)-3 A compound (9b)-2 can be obtained by an addition reaction of a compound (9b)-1.

A compound (9b)-1 can be converted to a compound (9b)-2 by using an equivalent or excessive amount of an addition reaction reagent in a solvent inert to the reaction at -78°C to a refluxing temperature. As an addition reaction reagent, a hydride reducing agent such as sodium borohydride or diiisobutylaluminum hydride or a metal reagent such as methyllithium or phenylmagnesium bromide may be mentioned.

A compound (9b)-3 can be obtained by reductive N-alkylation of a compound (9b)- 1 through formation of an imine.

A compound (9b)-1 can be converted to a compound (9b)-3 by using equivalent or excessive amounts of R NH and a hydride reducing agent such as sodium cyanoborohydride or sodium triacetoxyborohydride in an appropriate solvent or in the absence of solvent at 0°C to a refluxing temperature. Microwave irradiation or the presence of an acid is sometimes effective for smooth progress of the reaction. A compound having a hydrogen atom as R can be obtained by using hydroxylamine or its equivalent instead of R NH and lithium aluminum hydride, zinc or a hydrogen atmosphere containing palladium-carbon as a reducing agent.

(Synthesis of starting materials 4b) The compounds (10b)-3, (11b)-3 and (12b)-3 can be produced, for example, through the following schemes (10b), (11b) and (12b) (wherein R is a hydrogen atom or a protective group such as a Ts group, a TIPS group or a SEM group, and the other symbols are the same as defined above).

O Cl O HN 3b b (R ) 4b X 1b b 4b R B (10b) H N Y 3b b (R ) n 1b 1b N N PR PR (10b)-1 (10b)-2 (10b)-3 O Cl 2b 3b b (R ) 3b b X 1b 6b b R H C R H C B 2 Y H N + (11b ) 3b b (R ) 1 1b n N R N (11b)-1 (11b)-2 (11b)-3 2b R O HN 2b R O 3b b 3b (R ) 1b b S 6b X L 6b R H C R H C H N b (12b ) Y + Y 3b b (R ) N 1b (12b)-1 (12b)-2 (12b)-3 A compound (10b)-1 can be converted to a compound (10b)-3 by using an equivalent or excessive amount of an amine derivative (10b)-2 in an appropriate solvent or in the absence of solvent at room temperature to a refluxing temperature. The substituent reaction is preferred to be carried out under microwave irradiation or sometimes in the presence of a base or may be carried out under the reaction conditions used for the Buchwald-Hartwig reaction (for example, by referring to Advanced Synthesis & Catalysis, 2004, 346, pp. 1599-1626). It is possible to appropriately combine tris(dibenzylideneacetone)dipalladium (0), tetrakis(triphenylphosphine)palladium(0), palladium (II) acetate or the like with 4,5- bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos), 2-dicyclohexylphosphino- 2’,6’-dimethoxybiphenyl (SPhos), 2-dicyclohexylphosphino-2’,4’,6’-triisopropylbiphenyl (XPhos) or the like, without particular restrictions.

Compounds (11b)-3 and (12b)-3 can be obtained by using a compound (11b)-1 and an amine derivative (11b)-2 or a compound (12b)-1 and an amine derivative (12b)-2, like a compound (10b)-3.

(Synthesis of starting materials 5b) The compounds (13b)-4 can be produced, for example, through the following scheme (13b) (wherein R is a hydrogen atom or a protective group such as a Ts group, a TIPS group or a SEM group, R is a hydrogen atom or a C alkyl group, and the other symbols are the same as defined above).

A compound (13b)-4 can be obtained by the Stille reaction of compounds (13b)-2 and (13b)-3 (for example, by referring Bulletin of the Chemical Society of Japan,1987,60,pp.767-768).

A compound (13b)-2 can be converted to a compound (13b)-4 by using an equivalent or excessive amount of a compound (13b)-3 in the presence of a palladium catalyst such as tetrakis(triphenylphosphine)palladium (0), bis(triphenylphosphine)palladium (II) dichloride or bis(acetonitrile)palladium (II) dichloride in an appropriate solvent or in the absence of solvent at room temperature to a refluxing temperature. The presence of an acid or a base is sometimes effective for smooth progress of the reaction.

A compound (13b)-2 can be obtained by oxidization of a compound (13b)-1 followed by a reaction of the resulting N-oxide derivative with a chlorination agent.

A compound (13b)-1 can be converted to a compound (13b)-2 by oxidation with an equivalent or excessive amount of an oxidizing agent such as m-chloroperbenzoic acid, peracetic acid or aqueous hydrogen peroxide in an appropriate solvent or in the absence of solvent at 0°C to a refluxing temperature, followed by a reaction of the resulting N-oxide derivative with an equivalent or excessive amount of a chlorination agent such as phosphorus oxychloride or methanesulfonyl chloride in an appropriate solvent or in the absence of solvent at room temperature to a refluxing temperature.

(Synthesis of starting materials 6b) The compounds (14b)-3 and (14b)-5 can be produced, for example, through the following scheme (14b) (wherein R is a hydrogen atom or a protective group such as a Ts group, a TIPS group or a SEM group, and the other symbols are the same as defined above).

Compounds (14b)-3 and (14b)-4 can be obtained by coupling of an anion formed from a compound (14b)-2.

A compound (14b)-2 can be converted to a compound (14b)-3 by lithiation using an equivalent or excessive amount of an organic metal reagent such as n-butyllithium or s-butyllithium in an appropriate solvent or in the absence of solvent at -78°C to room temperature followed by coupling with an electrophilic reagent such as N,N- 4b Q 4b Q 4b Q Q Q dimethylformamide, R CO R , R CONR or R C(O)N(OR )R (wherein R is a hydrogen atom or a C alkyl group).

A compound (14b)-2 can be converted to a compound (14b)-4 by lithiation using an equivalent or excessive amount of an organic metal reagent such as n-butyllithium or s-butyllithium in an appropriate solvent or in the absence of solvent at -78°C to room temperature followed by coupling with an electrophilic reagent such as (R CH S) .

A compound (14b)-4 can be converted to a compound (14b)-5 by using an equivalent or excessive amount of an oxidizing agent such as m-chloroperbenzoic acid, peracetic acid or aqueous hydrogen peroxide in an appropriate solvent or in the absence of solvent at 0°C to a refluxing temperature.

A compound (14b)-1 can be converted to a compound (14b)-2 by oxidation with an equivalent or excessive amount of an oxidizing agent such as m-chloroperbenzoic acid, peracetic acid or aqueous hydrogen peroxide in an appropriate solvent or in the absence of solvent at 0°C to a refluxing temperature, followed by a reaction of the resulting N-oxide derivative with an equivalent or excessive amount of a chlorination agent such as phosphorus oxychloride or methanesulfonyl chloride in an appropriate solvent or in the absence of solvent at room temperature to a refluxing temperature.

(Synthesis of starting materials 7b) The compounds (15b)-4 can be produced, for example, through the following scheme (15b) (wherein R is a hydrogen atom or a protective group such as a Ts group, a TIPS group or a SEM group).

A compound (15b)-4 can be obtained by bromination or iodination of a compound (15b)-2 followed by dehydrogenation of the resulting compound (15b)-3.

A compound (15b)-3 can be converted to a compound (15b)-4 by using a catalyst such as palladium-carbon or manganese dioxide in an appropriate solvent or in the absence of solvent at room temperature to a refluxing temperature.

A compound (15b)-2 can be converted to a compound (15b)-3 by using an equivalent or excessive amount of a halogenating agent such as bromine, N- bromosuccinimide, iodine or N-iodosuccinimide in an appropriate solvent or in the absence of solvent at 0°C to a refluxing temperature.

A compound (15b)-1 can be converted to a compound (15b)-2 in the presence of a palladium-carbon catalyst under a hydrogen atmosphere in an appropriate solvent or in the absence of solvent at room temperature to a refluxing temperature.

(Synthesis of starting materials 8b) The compounds (16b)-2 can be produced, for example, through the following scheme (16b).

A compound (16b)-1 can be converted to a compound (16b)-2 by using an 16b Q 16b Q Q equivalent or excessive amount of R CO R or R C(OR ) (wherein R is a hydrogen atom or a C alkyl group) in an appropriate solvent or in the absence of solvent at room temperature to a refluxing temperature.

For synthesis of 7-azaindole or 1-deazapurine, the following general methods may be referred to.

As general methods for synthesis of 7-azaindole, those disclosed in Current Organic Chemistry,2001,5,pp.471-506 are known.

As general methods for synthesis of 1-deazapurine, those disclosed in Shin-pen Hetero-kan Kagoubutsu Ouyou-hen (Kodansha, 2004) pp.233-251 are known.

(Synthesis of starting materials 9b) The amine compounds (17b)-1 can be produced from the corresponding nitrile compounds, acid amide compounds, oxime compounds, halogen compounds, ketone compounds, aldehyde compounds, alcohol compounds, boron compounds, epoxide compounds, acid imide compounds and carbamate compounds (for example, by referring to Jikken Kagaku Koza vol. 20 Yuki Gosei II, edited by the Chemical Society of Japan, published by MARUZEN Co., Ltd., 1992; Bioorganic & Medicinal Chemistry, 13, 4022, 2005, Kuramochi T. et al.; Journal of Medicinal Chemistry, 50, 149, 2007; Journal of Organic Chemistry, 46, 4296, 1981; Journal of Organic Chemistry, 44, 2081, 1979; Acta Chemica Scandinavica, 19, 1741, 1965; and Organic Letters, 5, 4497, 2003).

Among the compounds represented by the formula (I ), the compounds (18b)-2 and (18b)-3 can be produced, for example, through the following scheme (18b) (wherein R is a hydrogen atom or a protective group such as a Ts group, a TIPS group or a SEM group, and the other symbols are the same as defined above).

A compound (18b)-3 can be obtained by cyclization of a compound (18b)-1 followed by a substitution reaction of the resulting compound (18b)-2.

A compound (18b)-1 can be converted to a compound (18b)-2 by using an equivalent or excessive amount of phosgene, phosgene dimer, phosgene trimer, 1,1’- carbonyldiimidazole, dimethyl carbonate, 1,1’-thiocarbonyldiimidazole , carbon disulfide or the like in an appropriate solvent or in the absence of solvent at room temperature to a refluxing temperature. The presence of an acid or a base or microwave irradiation is sometimes effective for smooth progress of the reaction.

A compound (18b)-2 can be converted to a compound (18b)-3 by using an 10b L equivalent or excessive amount of an electrophilic reagent represented by R -R (wherein R is a leaving group such as a chlorine atom, a methanesulfonyloxy group or a p-toluenesulfonyloxy group) such as an alkyl halide, an alkyl mesylate or an aryl halide in the presence of a base such as triethylamine in an appropriate solvent or in the absence of solvent at room temperature to a refluxing temperature. Microwave irradiation is sometimes effective for smooth progress of the reaction. A compound (18b)-2 can also be converted to a compound (18b)-3 by using equivalent or excessive amounts of a primary or secondary alcohol, a Mitsunobu reagent and a phosphine reagent in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature. As a Mitsunobu reagent, diethyl azodicarboxylate, diisopropyl azodicarboxylate or the like may be mentioned, and as a phosphine reagent, triphenylphosphine, tributylphosphine or the like may be mentioned.

A compound (18b)-2 or (18b)-3 having an oxygen atom as Y can be converted to a compound (18b)-2 or (18b)-3 having a sulfur atom as Y by using an equivalent or excessive amount of a thiocarbonylation agent such as phosphorus pentasulfide or Lawesson's reagent in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature.

A compound (18b)-2 or (18)-3 having a protective group as R can be converted to a compound having a hydrogen atom as R by deprotection.

Among the compounds represented by the formula (I ), the compounds (19b)-2 and (19b)-3 can be produced, for example, through the following scheme (19b) (wherein R is a hydrogen atom or a protective group such as a Ts group, a TIPS group or a SEM group, R is a benzyl type protective group such as a benzyl group or a benzyloxycarbonyl group, m is 0~3, and the other symbols are the same as defined above).

A compound (19b)-3 can be obtained by deprotection of the R in a compound (19b)-1 among the compounds (2b)-2 followed by a substitution reaction of the resulting compound (19b)-2.

A compound (19b)-1 having a benzyl type protective group as R can be converted to a compound (19b)-2 by using a catalytic amount of palladium-carbon under a hydrogen atmosphere in an appropriate solvent at room temperature to a refluxing temperature. The presence of an acid is sometimes effective for smooth progress of the reaction.

A compound (19b)-2 can be converted to a compound (19b)-3 by using equivalent 2b 3b 2b L or excessive amounts of an electrophilic reagent represented by R L L -R (wherein R is a leaving group such as a halogen atom, a methanesulfonyloxy group or a p- toluenesulfonyloxy group) such as an alkyl halide, an acid chloride, a sulfonyl chloride, a chloroformate ester, an isocyanate or an isothiocyanate and a base such as triethylamine in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature. A compound (19b)-2 can also be converted to a compound (19b)-3 by using an equivalent or excessive amount of an aldehyde or a ketone in the presence of a hydride reducing agent such as sodium cyanoborohydride or 2-picoline borane in an appropriate solvent or in the absence of solvent at 0°C to a refluxing temperature. Microwave irradiation or the presence of an acid is sometimes effective for smooth progress of the reaction.

A compound (19b)-3 having a protective group as R can be converted to a compound having a hydrogen atom as R by deprotection.

Among the compounds represented by the formula (I ), the compounds (20b)-2 and (20b)-3 can be produced, for example, through the following scheme (20b) (wherein R is a hydrogen atom or a protective group such as a Ts group, a TIPS group or a SEM group, R is a benzyl type protective group such as a benzyl group or a benzyloxycarbonyl group, m is 0, 1, 2 or 3 and the other symbols are the same as defined above).

A compound (20b)-3 can be obtained by deprotection of the R in a compound (20b)-1 among the compounds (18b)-3 followed by a substitution reaction of the resulting compound (20b)-2.

A compound (20b)-1 having a benzyl type protective group as R can be converted to a compound (20b)-2 by using a catalytic amount of palladium-carbon under a hydrogen atmosphere in an appropriate solvent at room temperature to a refluxing temperature. The presence of an acid is sometimes effective for smooth progress of the reaction.

A compound (20b)-2 can be converted to a compound (20b)-3 by using equivalent 2b 3b 2b L or excessive amounts of an electrophilic reagent represented by R L L -R (wherein R is a leaving group such as a halogen atom, a methanesulfonyloxy group or a p- toluenesulfonyloxy group) such as an alkyl halide, an acid chloride, sulfonyl chloride, a chloroformate, an isocyanate or an isothiocyanate and a base such as triethylamine in an appropriate solvent or in the absence of solvent at -78°C to a refluxing temperature.

A compound (20b)-2 can also be converted to a compound (20b)-3 by using an equivalent or excessive amount of an aldehyde or a ketone in the presence of a reducing agent such as sodium cyanoborohydride or 2-picoline borane in an appropriate solvent or in the absence of solvent at 0°C to a refluxing temperature. Microwave irradiation or the presence of an acid is sometimes effective for smooth progress of the reaction.

A compound (20b)-3 having a protective group as R can be converted to a compound having a hydrogen atom as R by deprotection.

Among the compounds represented by the formula (I ), the compounds (21b)-2, (21b)-3 and (21b)-4 can be produced, for example, through the following scheme (21b) (wherein R is a hydrogen atom or a protective group such as a Ts group, a TIPS group or a SEM group, R is a protective group such as a benzyl group or an acetyl group, R is a hydrogen atom or a C alkyl group, m is 0, 1, 2 or 3, and the other symbols are the same as defined above). 3b b (R ) 3b b 3b b (R ) (R ) Y A Z A Z 10b 10b N N PR3 N N N N ( ) ( ) OH O O X X b O O 1b 1b R N R N PR PR (21b)-1 (21b)-2 (21b)-3 (21b) 3b b (R ) 2b 12b R R A ( ) N R (21b)-5 m (21b)-4 A compound (21b)-1 among the compounds (18b)-3 is converted to a compound (21b)-2 by deprotection.

A compound (21b)-2 can be converted to a compound (21b)-3 by oxidation with an equivalent or excessive amount of an oxidizing agent such as 2-iodoxybenzoic acid or pyridinium chlorochromate in an appropriate solvent or in the absence of solvent at - 78°C to a refluxing temperature.

A compound (21b)-3 can be converted to a compound (21b)-4 by using equivalent or excessive amounts of a compound (21b)-5 and a reducing agent such as 2-picoline borane or sodium triacetoxyborohydride in an appropriate solvent or in the absence of solvent at room temperature to a refluxing temperature.

Compounds (21b)-3 and (21b)-4 having a protective group as R can be converted to compounds (21b)-3 and (21b)-4 having a hydrogen atom as R by deprotection.

In the present invention, the tricyclic pyrimidine compounds of the present invention represented by the formula (I ) and the tricyclic pyridine compounds of the present invention represented by the formula (I ) may be present in the form of tautomers or geometrical isomers which undergo endocyclic or exocyclic isomerization, mixtures of tautomers or geometric isomers or mixtures of thereof. When the compounds of the present invention have an asymmetric center, whether or not resulting from an isomerization, the compounds of the present invention may be in the form of resolved optical isomers or in the form of mixtures containing them in certain ratios. Further, when the compounds of the present invention have two or more asymmetric centers, the compounds of the present invention can be in the form of diastereomers due to optical isomerism about them. The compounds of the present invention may be in the form of a mixture of all these isomers in certain ratios. For example, diastereomer can be separated by techniques well known to those skilled in the art such as fractional crystallization, and optical isomers can be obtained by techniques well known in the field of organic chemistry for this purpose.

The tricyclic pyrimidine compounds of the present invention represented by the formula (I ) and the tricyclic pyridine compounds of the present invention represented by the formula (I ) or pharmaceutically acceptable salts thereof may be in the form of arbitrary crystals or arbitrary hydrates, depending on the production conditions. The present invention covers these crystals, hydrates and mixtures. They may be in the form of solvates with organic solvents such as acetone, ethanol, 1-propanol and 2- propanol, and the present invention covers any of these forms.

The present invention covers pharmaceutically acceptable salts of the compounds of the present invention represented by the formulae (I ) and (I ).

The compounds of the present invention represented by the formulae (I ) and (I ) may be converted to pharmaceutically acceptable salts or may be liberated from the resulting salts, if necessary. The pharmaceutically acceptable salts of the present invention may be, for example, salts with alkali metals (such as lithium, sodium and potassium), alkaline earth metals (such as magnesium and calcium), ammonium, organic bases, amino acids, inorganic acids (such as hydrochloric acid, hydrobromic acid, phosphoric acid and sulfuric acid) and organic acids (such as acetic acid, citric acid, maleic acid, fumaric acid, tartaric acid, benzenesulfonic acid, methanesulfonic acid and p-toluenesulfonic acid).

The present invention covers prodrugs of the compounds of the present invention represented by the formulae (I ) and (I ).

Prodrugs are derivatives of medicinal compounds having chemically or metabolically degradable groups and give pharmacologically active medicinal compounds upon solvolysis or under physiological conditions in vivo. Methods for selecting or producing appropriate prodrugs are disclosed in, for example, Design of Prodrugs (Elsevier, Amsterdam 1985). In the present invention, in the case of a compound having a hydroxy group, prodrugs like acyloxy derivatives obtained by reacting the compound with appropriate acyl halides, appropriate acid anhydrides or appropriate haloalkoxycarbonyl compounds may, for example, be mentioned.

Structures particularly preferred as prodrugs include -OCOC H , -OCO(t-Bu), - OCOC H , -OCO(m-CO Na-Ph), -OCOCH CH CO Na, -OCOCH(NH )CH , - 31 2 2 2 2 2 3 OCOCH N(CH ) , -O-CH OC(=O)CH or the like. In the case of a compound having 2 3 2 2 3 an amino group, prodrugs obtained by reacting the compound having an amino group with appropriate acid halides, appropriate mixed acid anhydrides or haloalkoxycarbonyl compounds may, for example, be mentioned. Structures particularly preferred as prodrugs include -NHCO(CH ) OCH , -NHCOCH(NH )CH , -NH-CH O(C=O)CH or 2 20 3 2 3 2 3 the like.

The JAK inhibitors and the preventive, therapeutic and/or improving agents for diseases against which inhibition of JAK is effective are those mentioned below among the tricyclic pyrimidine compounds and the tricyclic pyridine compounds of the present invention. a a b 1) JAK inhibitors containing the compounds as defined in any one of 1 ) to 62 ) and 1 ) to 44 ), tautomers or pharmaceutically acceptable salts of the compounds or solvates 40 thereof, as an active ingredient. 2) Preventive, therapeutic or improving agents for diseases against which inhibition of JAK is effective, which contains the JAK inhibitors as defined in 1) as an active ingredient. 3) Therapeutic agents for rheumatoid arthristis, which contain the JAK inhibitors as 45 defined in 1) as an active ingredient. a a b 4) Medicaments containing the compound as defined in any one of 1 ) to 62 ) and 1 ) to 44 ), tautomers or pharmaceutically acceptable salts of the compounds or solvates thereof, as an active ingredient.

The preventive, therapeutic and improving agents for diseases against which inhibition of JAK is effective which contain the JAK inhibitors of the present invention, as an active ingredient may usually be administered as oral medicines such as tablets, capsules, powder, granules, pills and syrup, as rectal medicines, percutaneous medicines or injections. The agents of the present invention may be administered as a single therapeutic agent or as a mixture with other therapeutic agents. Though they may be administered as they are, they are usually administered in the form of medical compositions. These pharmaceutical preparations can be obtained by adding pharmacologically and pharmaceutically acceptable additives by conventional methods.

Namely, for oral medicines, ordinary additives such as excipients, lubricants, binders, disintegrants, humectants, plasticizers and coating agents may be used. Oral liquid preparations may be in the form of aqueous or oily suspensions, solutions, emulsions, syrups or elixirs or may be supplied as dry syrups to be mixed with water or other appropriate solvents before use. Such liquid preparations may contain ordinary additives such as suspending agents, perfumes, diluents and emulsifiers. In the case of rectal administration, they may be administered as suppositories. Suppositories may use an appropriate substance such as cacao butter, laurin tallow, Macrogol, glycerogelatin, Witepsol, sodium stearate and mixtures thereof as the base and may, if necessary, contain an emulsifier, a suspending agent, a preservative and the like. For injections, pharmaceutical ingredients such as distilled water for injection, physiological saline, 5% glucose solution, propylene glycol and other solvents or solubilizing agents, a pH regulator, an isotonizing agent and a stabilizer may be used to form aqueous dosage forms or dosage forms which need dissolution before use.

The dose of the agents of the present invention for administration to human is usually about from 0.1 to 1000 mg/body/day in the case of oral drugs or rectal administration and about from 0.05 mg to 500 mg/body/day in the case of injections, though it depends on the age and conditions of the patient. The above-mentioned ranges are mere examples, and the dose should be determined from the conditions of the patient.

The present invention is used when it is expected to improve pathology of diseases associated with JAK1, JAK2 and JAK3 separately or in combination. Among these diseases, JAK3-associated diseases are, in addition to rheumatoid arthristis, inflammatory or proliferative dermatoses such as psoriasis, atopic dermatitis, contact dermatitis, eczematoid dermatitis, seborrheic dermatitis, lichen planus, pemphigus, pemphigoid, epidermolysis bullosa, hives, angioedema, angiitis, erythema, dermal eosinophilia, lupus erythematosus, acne, alopecia areata, immune dermatoses, reversible airway obstruction, mucitis and angitis. Among these diseases, JAK3- and JAK1-associated diseases are, in addition to rheumatoid arthristis, asthma, atopic 40 dermatitis, Alzheimer disease, atherosclerosis, cancer, leukemia, rejection of organ or tissue grafts (such as heart, kidney, liver, bone marrow, skin, horn, lung, pancreas, islet, small intestine, extremities, muscles, nerves, intervertebral disks, trachea, myoblasts and cartilage), graft-versus-host reaction after bone marrow transplantation and autoimmune diseases such as rheumatic disease, systemic lupus erythematosus (SLE), 45 Hashimoto's disease, multiple sclerosis, myasthenia gravis, type I diabetes and diabetic complications. Among these diseases, JAK2-associated diseases include, for example, myeloproliferative disorders.

As an application of the present invention, treatment and prevention of the above- mentioned diseases may be mentioned, but there is no restriction.

Compounds of the present invention are administered either alone or in combination with one or more additional agents such as immunomodulators, antiinflammatory agents or antirheumatic drugs. The additional agents may be cyclosporin A, tacrolimus, leflunomide, deoxyspergualin, mycophenolate, azathioprine, ® ® ® etanercept (e.g. Enbrel ), infliximab (e.g. Remicade ), adalimumab (e.g. Humira ), ® ® ® certolizumab pegol (e.g. Cimzia ), Golimumab (e.g. Simponi ), Anakinra (e.g. Kineret ), rituximab (e.g. Rituxan ), Tocilizumab (e.g. Actemra ), methotrexate, aspirin, acetaminophen, ibuprofen, naproxen, piroxicam, and antiinflmmatory steroids (e.g. prednisolone or dexamethasone), but are not restricted thereto.

Now, the present invention will be described in further detail with reference to Reference Synthetic Examples, Synthetic Examples, Assay Examples and Formulation Examples. However, it should be understood that the present invention is by no means restricted by these specific Examples. In the Examples, “NMR” denotes nuclear magnetic resonance, “LC/MS” denotes high performance liquid chromatography-mass spectrometry, “v/v” means volume ratio. In the tables, “Rf” denotes Reference Synthetic Example, “Ex” denotes Synthetic Example, “Structure” denotes chemical structural formula, “diastereomixture” denotes a diastereomeric mixture, “racemate” denotes a racemic mixture, “cis/trans mixture” denotes a cis- and trans-isomeric mixture, and “E/Z mixture” denotes a E- and Z-isomeric mixture, and “Data” denotes physical property data, “condition” denotes measurement condition, “retention time” denotes retention time in LC/MS, “Compound Name” denotes compound name of the synthesized compound, “Morphology” denotes morphology of a synthesized compound, “Yield” denotes yield of a synthesized compound, “quant” denotes quantitative, “min” denotes minute.

In the Examples herein, “rac-“ or “racemate” used in texts or tables for a compound having more than one asymmetric center means that the compound is in the form of a racemic mixture of the specified absolute configuration and its enantiomer.

The H-NMR data show chemical shifts δ (unit : ppm) (splitting pattern, value of integral) measured at 300 MHz (with JNM-ECP300, manufactured by JEOL Ltd or JNM- ECX300, manufactured by JEOL Ltd) using tetramethylsilane as an internal standard. “s” denotes “singlet”, “d” denotes “doublet”, “t” denotes “triplet”, “q” denotes “quartet “, “quint” denotes quintet, “sextet” denotes sextet, “septet” denotes septet, “dd” denotes doublet of doublets, “dt” denotes doublet of triplets, “td” denotes triplet of doublets, “dq” denotes doublet of quartets, “qd” denotes quartet of doublets, “tt” denotes triplet of triplets, “ddd” denotes doublet of doublet of doublets, “m” denotes multiplet, “br” denotes broad, “J” denotes coupling constant, “CDCl ” denotes deuterated chloroform, “CD OD” denotes deuterated methanol, and “DMSO-d ” denotes deuterated dimethyl sulfoxide. 40 For purification by silica gel column chromatography, Hi Flash column manufactured by Yamazen Corporation, a silica gel 60 manufactured by Merck & Co., Inc. or PSQ60B manufactured by Fuji Silysia Chemical Ltd. was used unless otherwise noted.

For purification by silica gel thin layer chromatography, PLC plate manufactured 45 by Merck & Co., Inc. was used unless otherwise noted.

As a microwave reactor, Initiator sixty manufactured by Biotage was used.

LC/MS spectra were measured by using ESI (electrospray ionization). “ESI ” denotes ESI-positive mode, and “ESI “ denotes ESI-negative mode.

LC/MS condition 1 Instrument: Waters Alliance-ZQ Column: Waters SunFire C18(3.5µm, 2.1×20mm) Column Temp.: 40°C Eluents: Liquid A: 0.1% aqueous formic acid Liquid B: 0.1% formic acid in acetonitrile Elution: A mixture of Liquids A and B was flown at 0.4 mL/min while the mixing ratio was linearly changed from 90/10 (v/v) to 15/85 (v/v) over the first 3 minutes, and then the flow rate was linearly changed to 0.5 mL/min for 2 minutes at a constant mixing ratio of 15/85 (v/v). Then, the mixing ratio was linearly changed to 90/10 (v/v) over 0.5 minute and maintained at 90/10 (v/v) for 2.5 minutes.

LC/MS condition 2 Instrument: Waters Alliance-ZQ Column: Waters SunFire C18(3.5µm, 2.1×20mm) Column Temp.: 40°C Eluents: Liquid A: 0.2% aqueous formic acid Liquid B: acetonitrile Elution: A mixture of Liquids A and B was flown at 0.4 mL/ min while the mixing ratio was linearly changed from 90/10 (v/v) to 15/85 (v/v) over the first 3 minutes, and then the flow rate was linearly changed to 0.5 mL/min over 2 minutes at a constant mixing ratio of 15/85 (v/v). Then, the mixing ratio was linearly changed to 95/5 (v/v) over 0.5 minute and maintained at 95/5 (v/v) for 1.5 minutes.

LC/MS condition 3 Instrument:: Thermo LTQ XL Column: Waters AQUITY UPLC BEH C18(1.7µm, 2.1×50mm) Column Temp.: 40°C Eluents: Liquid A: 0.1% aqueous formic acid Liquid B: 0.1% formic acid in acetonitrile Elution: A mixture of Liquids A and B was flown at 0.6 mL/min at a mixing ratio of 90/10 (v/v) for the first 0.5 minutes, and then the mixing ratio was linearly changed to /90 (v/v) over 2.5 minutes and then maintained at 10/90 (v/v) for 0.7 minute. The mixing ratio and the flow rate were linearly changed to 90/10 (v/v) and 0.8 mL/min, respectively, over 0.1 minute, maintained constant for 1 minute and linearly changed to 90/10 (v/v) and 0.6 mL/min, respectively, over 0.1 minute.

REFERENCE SYNTHETIC EXAMPLE 1 4-Iodo-7H-pyrrolo[2,3-d]pyrimidine Hydroiodic acid (55 wt%, 100g) was mixed with 4-chloro-7H-pyrrolo[2,3- d]pyrimidine (manufactured by Tokyo Chemical Industry Co., Ltd., 10.6 g, 69.0 mmol) under cooling with ice and stirred at 0°C for 1 hour and then at room temperature for one day. The precipitated solid was collected by filtration and washed with water.

The residue was suspended in water, neutralized with 1 M aqueous sodium hydroxide and filtered. The yellow solid was washed with water and dried under reduced pressure to give the title compound as a yellow solid (16.2 g, yield 96%, including 10% 4-chloro-7H-pyrrolo[2,3-d]pyrimidine as the starting compound).

REFERENCE SYNTHETIC EXAMPLE 2 4-Iodo(triisopropylsilyl)-7H-pyrrolo[2,3-d]pyrimidine 4-Iodo-7H-pyrrolo[2,3-d]pyrimidine (352 mg, 1.44 mmol) in tetrahydrofuran (15 mL) cooled to 0°C was mixed with sodium hydride (55 wt% dispersion in mineral oil, 75.5 mg, 1.73 mmol) and chlorotriisopropylsilane (0.37 mL, 1.7 mmol) and stirred at room temperature for 45 minutes. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate =100/1 (v/v)) to give the title compound as a pale yellow oil (431 mg, yield 74%).

REFERENCE SYNTHETIC EXAMPLE 3 Cyclohexyl[7-(triisopropylsilyl)-7H-pyrrolo[2,3-d]pyrimidinyl]methanol n-Butyllithium (1.6 M solution in hexane, 0.23 mL, 0.380 mmol) was gradually added dropwise to 4-iodo(triisopropylsilyl)-7H-pyrrolo[2,3-d]pyrimidine (126 mg, 0.310 mmol) in tetrahydrofuran (1.5 mL) cooled to -78°C, and the reaction mixture was stirred at -78°C for 30 minutes. After addition of cyclohexanecarbaldehyde (42 µL, 0.35 mmol) in tetrahydrofuran (1.5 mL), the reaction mixture was gradually warmed from -78°C to room temperature and stirred for one day. After addition of saturated aqueous ammonium chloride, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Hi Flash column amino type manufactured by Yamazen Corporation: hexane / ethyl acetate = /1 → 7/1 → 4/1 (v/v)) to give the title compound as a colorless oil (65.5 mg, yield 55%).

REFERENCE SYNTHETIC EXAMPLE 4 Cyclohexyl[7-(triisopropylsilyl)-7H-pyrrolo[2,3-d]pyrimidinyl]methanone Cyclohexyl[7-(triisopropylsilyl)-7H-pyrrolo[2,3-d]pyrimidinyl]methanol (211 mg, 0.540 mmol) in dichloromethane (7 mL) was stirred with 1,1,1-triacetoxy-1,1-dihydro- 1,2-benziodoxol-3(1H)-one (347 mg, 0.820 mmol) at room temperature for 2.5 hours. 40 After addition of a mixture (1/1 (v/v)) of saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium thiosulfate, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ ethyl acetate = 30/1 (v/v)) to give the title compound as a 45 colorless solid (117 mg, yield 55%).

REFERENCE SYNTHETIC EXAMPLE 5 Cyclohexyl(7H-pyrrolo[2,3-d]pyrimidinyl)methanone Cyclohexyl[7-(triisopropylsilyl)-7H-pyrrolo[2,3-d]pyrimidinyl]methanone (22.4 mg, 58.0 µmol) was stirred with hydrogen chloride - methanol solution (10 wt%, 2.0 mL) at room temperature for 15 minutes. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (Hi Flash column amino type manufactured by Yamazen Corporation: chloroform / methanol = 10/1 (v/v)) to give the title compound as a pale yellow oil (9.2 mg, yield 69%).

REFERENCE SYNTHETIC EXAMPLE 6 Cyclohexyl(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin yl)methanone Cyclohexyl(7H-pyrrolo[2,3-d]pyrimidinyl)methanone (50.0 mg, 0.218 mmol) in N,N-dimethylformamide (1 mL) was mixed with sodium hydride (60 wt% dispersion in mineral oil, 9.6 mg, 0.24 mmol) and [2-(chloromethoxy)ethyl]trimethylsilane (42.5 µL, 0.240 mmol) under cooling with ice and stirred for 30 minutes while the temperature was gradually raised to room temperature. Separately, cyclohexyl(7H-pyrrolo[2,3- d]pyrimidinyl)methanone (500 mg, 2.18 mmol) in N,N-dimethylformamide (5 mL) was mixed with sodium hydride (60 wt% dispersion in mineral oil, 96 mg, 2.4 mmol) and (chloromethoxy)ethyl]trimethylsilane (425 µL, 2.40 mmol) under cooling with ice and stirred for 30 minutes while the temperature was gradually raised to room temperature.

After addition of water, the reaction solution and the previously obtained reaction solution were extracted with ethyl acetate, respectively, and the organic layers were washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residues were combined and purified by silica gel column chromatography (hexane/ ethyl acetate =5/1 (v/v)) to give the title compound as a pale yellow oil (850 mg, yield 99%).

REFERENCE SYNTHETIC EXAMPLE 7 Cyclohexyl(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin yl)methanamine Cyclohexyl(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin yl)methanone (406 mg, 1.13 mmol) in methanol (10 ml) was stirred with hydroxylamine hydrochloride (395 mg, 5.66 mmol) for 4 hours. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in ethanol (3.0 mL), mixed with ammonium acetate (105 mg, 1.36 mmol), water (3 mL) and aqueous ammonia (5 mL) and refluxed with zinc powder (600 mg, 9.17 mmol) for 4 hours. The reaction mixture was allowed to cool to room temperature and filtered, and the filtrate was concentrated under reduced pressure.

The residue was purified by silica gel column chromatography (Hi Flash column amino type manufactured by Yamazen Corporation: chloroform / methanol = 20/1 (v/v)) to give the title compound as a yellow oil (390 mg, yield 79%). 40 REFERENCE SYNTHETIC EXAMPLE 8 1-Cyclohexyl{[2-(trimethylsilyl)ethoxy]methyl}-7H-imidazo[1,5-c]pyrrolo[3,2- e]pyrimidine Cyclohexyl(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin yl)methanamine (10 mg. 0.028 mmol) in N,N-dimethylformamide dimethyl acetal (0.7 45 mL) was stirred at 170°C for 30 minutes under microwave irradiation. The reaction mixture was allowed to cool to room temperature and concentrated under reduced pressure, and the resulting residue was dissolved in 1,3-dimethylimidazolidinone (1.0 mL) and stirred at 230°C for 1.5 hours under microwave irradiation. Separately, cyclohexyl(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin ylmethanamine (89 mg, 0.25 mmol) in N,N-dimethylformamide dimethyl acetal (1 mL) was stirred at 170°C for 30 minutes under microwave irradiation. The reaction mixture was allowed to cool to room temperature and concentrated under reduced pressure, and the resulting residue was dissolved in 1,3-dimethylimidazolidinone (4.5 mL) and stirred at 230°C for 1.5 hours under microwave irradiation. The reaction mixture and the previously obtained reaction mixture were combined, diluted with ethyl acetate, acidified with 1 M hydrochloric acid and washed with saturated aqueous ammonium chloride and saturated aqueous sodium chloride, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (hexane / ethyl acetate = 2/1 → 1/1 →1/2 (v/v)) to give the title compound as a pale yellow oil (31.4 mg, yield 30%).

REFERENCE SYNTHETIC EXAMPLE 9 N-Methoxy-N,2-dimethylbenzamide 2-Methylbenzoic acid (1.00 g, 7.34 mmol) and 1-(3-dimethylaminopropyl) ethylcarbodiimide hydrochloride (1.69 g, 8.81 mmol) in chloroform (10 mL) stirred with N,N-diisopropylethylamine (1.50 mL, 8.81 mmol) for 10 minutes under cooling with ice and then stirred with N,O-dimethylhydroxylamine hydrochloride (860 mg, 8.81 mmol) and N,N-diisopropylethylamine (1.50 mL, 8.81 mmol) for one day while the temperature was gradually raised to room temperature. After addition of water, the reaction mixture was extracted with chloroform, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1/1 (v/v)) to give the title compound as a pale yellow oil (658 mg, yield 50%).

REFERENCE SYNTHETIC EXAMPLE 10 (7H-Pyrrolo[2,3-d]pyrimidinyl)(o-tolyl)methanone Isopropylmagnesium chloride (2.0 M solution in tetrahydrofuran, 1.05 mL, 2.10 mmol) was gradually added dropwise to 4-iodo-7H-pyrrolo[2,3-d]pyrimidine (245 mg, 1.00 mmol) obtained in Reference Synthetic Example 1 in tetrahydrofuran (5 mL) cooled to -78°C, and the resulting reaction mixture was stirred at -78°C for 15 minutes.

The reaction mixture was warmed to room temperature and stirred with (2,6- dimethylphenyl)magnesium bromide (1.0 M solution in tetrahydrofuran, 1.1 mL, 1.1 mmol) and N-methoxy-N,2-dimethylbenzamide (180 mg, 1.00 mmol) in tetrahydrofuran (4 mL) at room temperature for one day. After addition of saturated aqueous ammonium chloride, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue 40 was purified by silica gel column chromatography (hexane/ ethyl acetate = 2/1 → 1/1 (v/v)) to give the title compound as a pale yellow solid (162 mg, yield 68%).

REFERENCE SYNTHETIC EXAMPLE 11 N-Methoxy-N-methylcyclohexanecarboxamide The reactions in Reference Synthetic Example 9 were carried out in substantially 45 the same manners except that cyclohexanecarboxylic acid was used instead of 2- methylbenzoic acid to give the title compound as a colorless oil (2.14 g, yield 46%).

REFERENCE SYNTHETIC EXAMPLE 12 Cyclohexyl(7H-pyrrolo[2,3-d]pyrimidinyl)methanone The reactions in Reference Synthetic Example 10 were carried out in substantially the same manners except that N-methoxy-N- methylcyclohexanecarboxamide was used instead of N-methoxy-N,2- dimethylbenzamide to give the title compound as a pale yellow solid (1.26 g, yield 67%).

REFERENCE SYNTHETIC EXAMPLE 13 N-Methoxy-N,2-dimethylcyclohexanecarboxamide The reactions in Reference Synthetic Example 9 were carried out in substantially the same manners except that 2-methylcyclohexanecarboxylic acid was used instead of 2-methylbenzoic acid to give the title compound as a colorless oil (623 mg, yield 48%).

REFERENCE SYNTHETIC EXAMPLE 14 (2-Methylcyclohexyl)(7H-pyrrolo[2,3-d]pyrimidinyl)methanone The reactions in Reference Synthetic Example 10 were carried out in substantially the same manners except that N-methoxy-N,2- dimethylcyclohexanecarboxamide was used instead of N-methoxy-N,2- dimethylbenzamide to give the title compound as a colorless solid (165 mg, yield 68%).

REFERENCE SYNTHETIC EXAMPLE 15 4-Iodo{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine 4-Iodo-7H-pyrrolo[2,3-d]pyrimidine (90 mg, 0.037 mmol) obtained in Reference Synthetic Example 1 in N,N-dimethylformamide (4 mL) was stirred with sodium hydride (55 wt% dispersion in mineral oil, 19.2 mg, 0.0440 mmol) and [2- (chloromethoxy)ethyl]trimethylsilane (77.9 µL, 0.0440 mmol) at room temperature for one day. After addition of saturated aqueous sodium chloride, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 10/1→ 4/1 (v/v)) to give the title compound as a colorless oil (115 mg, yield 83%).

REFERENCE SYNTHETIC EXAMPLE 16 Benzyl 3-(hydroxymethyl)piperidinecarboxylate 3-Piperidinemethanol (3.59 g, 31.2 mmol) in 1,4-dioxane (8 mL) was mixed with potassium carbonate (4.55 g, 33.0 mmol), 1 M aqueous sodium hydroxide (2 mL) and benzyl chloroformate (5.20 mL, 36.4 mmol) under cooling with ice and stirred at room temperature for one day. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous potassium hydrogen sulfate and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1/1 (v/v)) to give the title compound as a colorless oil (6.41 g, yield 83%).

REFERENCE SYNTHETIC EXAMPLE 17 40 Benzyl 3-[methoxy(methyl)carbamoyl]piperidinecarboxylate Benzyl 3-(hydroxymethyl)piperidinecarboxylate (2.0 g, 8.0 mmol) in dichloromethane (50 mL) was stirred with 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol- 3(1H)-one (5.1 g, 12 mmol) at room temperature for 2.5 hours. After addition of a mixture (1/1(v/v)) of saturated aqueous sodium hydrogen carbonate and saturated 45 aqueous sodium thiosulfate, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in t-butanol (25 mL), mixed with sodium dihydrogen phosphate (2.89 g, 24.1 mmol), water (25 mL) and 2-methyl butene (25 mL, 241 mmol), then stirred with sodium chlorite (3.62 g, 40.1 mmol) at 0°C for 1 hour and then stirred at room temperature for 1 hour. After addition of saturated aqueous sodium thiosulfate, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in N,N-dimethylformamide (60 mL) and mixed with N,O-dimethylhydroxylamine hydrochloride (1.02 g, 10.4 mmol) and O-(7-azabenzotriazolyl)-N,N,N’,N’-tetramethyluronium hexafluorophosphate (4.0 g, .4 mmol) and then stirred with triethylamine (1.5 mL, 10 mmol) at room temperature for 2.5 hours. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 3/1 → 1/1 (v/v)) to give the title compound as a pale yellow oil (1.44 mg, yield 59% (three steps)).

REFERENCE SYNTHETIC EXAMPLE 18 Benzyl 3-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine carbonyl)piperidinecarboxylate Isopropylmagnesium chloride (2.0 M solution in tetrahydrofuran, 0.4 mL, 0.80mmol) was gradually added dropwise to 4-iodo{[2-(trimethylsilyl)ethoxy]methyl}- 7H-pyrrolo[2,3-d]pyrimidine (200 mg, 0.530 mmol) obtained in Reference Synthetic Example 15 in tetrahydrofuran (3 mL) cooled to -78°C, and the resulting reaction mixture was stirred at -78°C for 15 minutes. The reaction mixture was warmed to room temperature and stirred with (2,6-dimethylphenyl)magnesium bromide (1.0 M solution in tetrahydrofuran, 0.8 mL, 0.80 mmol) and benzyl 3- [methoxy(methyl)carbamoyl]piperidinecarboxylate (245 mg, 0.800 mmol) in tetrahydrofuran (3.0 mL) at room temperature for 2.5 hours. After addition of saturated aqueous ammonium chloride, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 4/1 → 2/1 → 1/1 (v/v)) to give the title compound as a yellow oil (107 mg, yield 41%).

REFERENCE SYNTHETIC EXAMPLE 19 Benzyl 3-[amino(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin yl)methyl]piperidinecarboxylate The reactions in Reference Synthetic Example 7 were carried out in substantially the same manners except that 3-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3- d]pyrimidinecarbonyl)piperidinecarboxylate (253 mg, 0.510 mmol) was used instead of cyclohexyl(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin yl)methanone to give the title compound as a pale blue oil (183 mg, yield 72%). 40 REFERENCE SYNTHETIC EXAMPLE 20 Benzyl 3-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-imidazo[1,5-c]pyrrolo[3,2-e]pyrimidin yl)piperidinecarboxylate Benzyl 3-[amino(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin yl)methyl]piperidinecarboxylate (63 mg, 0.13 mmol) in N,N-dimethylformamide 45 dimethyl acetal (1 mL) was stirred at 170°C for 30 minutes under microwave irradiation.

The reaction mixture was allowed to cool to room temperature and concentrated under reduced pressure, and the resulting residue was dissolved in 1,3-dimethylimidazolidin- 2-one (1 mL) and stirred at 230°C for 1.5 hours under microwave irradiation. The reaction mixture was allowed to cool to room temperature, diluted with ethyl acetate and washed with saturated aqueous ammonium chloride and saturated aqueous sodium chloride, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel thin layer chromatography (hexane / ethyl acetate = 1/1 → 1/2 (v/v)) to give a brown oil containing the title compound (45.2 mg). The resulting mixture was used for the next step.

REFERENCE SYNTHETIC EXAMPLE 21 trans(Hydroxymethyl)-N-methoxy-N-methylcyclohexanecarboxamide The reactions in Reference Synthetic Example 9 were carried out in substantially the same manners except that trans(hydroxylmethyl)cyclohexanecarboxylic acid (manufactured by Tokyo Chemical Industry Co., Ltd.) was used instead of 2- methylbenzoic acid to give the title compound as a colorless oil (515 mg, yield 41%).

REFERENCE SYNTHETIC EXAMPLE 22 trans[(tert-Butyldiphenylsilyloxy)methyl]-N-methoxy-N- methylcyclohexanecarboxamide trans(Hydroxymethyl)-N-methoxy-N-methylcyclohexanecarboxamide (403 mg, 2.00 mmol) in N,N-dimethylformamide (4 mL) was mixed with tert- butylchlorodiphenylsilane (514 µL, 2.00 mmol) and 1H-imidazole (136 mg, 2.00 mmol) under cooling with ice and stirred for one day while the temperature was gradually raised to room temperature. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 8/1 (v/v)) to give the title compound as a colorless oil (536 mg, yield 61%).

REFERENCE SYNTHETIC EXAMPLE 23 {trans[(tert-Butyldiphenylsilyloxy)methyl]cyclohexyl}(7H-pyrrolo[2,3-d]pyrimidin yl)methanone The reactions in Reference Synthetic Example 10 were carried out in substantially the same manners except that trans[(tert-butyldiphenylsilyloxy)methyl]- N-methoxy-N-methylcyclohexanecarboxamide was used instead of N-methoxy-N,2- dimethylbenzamide to give the title compound as a yellow oil (111 mg, yield 59%).

REFERENCE SYNTHETIC EXAMPLE 24 1-{trans[(tert-Butyldiphenylsilyloxy)methyl]cyclohexyl}-7H-pyrrolo[3,2- e][1,2,3]triazolo[1,5-c]pyrimidine The reactions in Synthetic Example 5 were carried out in substantially the same manners except that {trans[(tert-butyldiphenylsilyloxy)methyl]cyclohexyl}(7H- 40 pyrrolo[2,3-d]pyrimidinyl)methanone obtained in Reference Synthetic Example 23 was used instead of (7H-pyrrolo[2,3-d]pyrimidinyl)(o-tolyl)methanone to give the title compound as a pale yellow solid (50.6 mg, yield 46%).

REFERENCE SYNTHETIC EXAMPLE 25 3-Methyl 1-tert-butyl 4-methylpiperidine-1,3-dicarboxylate 45 4-Methylpyridinecarboxylic acid (1.13 g, 6.48 mmol) in methanol (20 mL) was refluxed with concentrated sulfuric acid (4.0 mL) for 2 days under heating. The reaction mixture was concentrated under reduced pressure, gradually adjusted to pH 8 or above with saturated aqueous sodium hydrogen carbonate and extracted with ethyl acetate twice. The resulting organic layer was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give a red oil (0.89 g). The reactions were carried out with 4-methylpyridinecarboxylic acid (1.77 g, 10.2 mmol) to give a red oil (1.37 g).

The red oil (2.26 g) obtained above was dissolved in ethyl acetate (35 mL) was stirred with active carbon (400 mg) at room temperature for 30 minutes. The mixture was filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in acetic acid (35 mL) and stirred with platinum(IV) oxide (162 mg) under a hydrogen atmosphere at 0.5 MPa for 3 days. The reaction mixture was filetered, and the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in acetonitrile (50 mL) and water (40 mL) and stirred with sodium hydrogen carbonate (5.00 g, 59.5 mmol) and tert-butyl bicarbonate (5.10 g, 23.4 mmol) for one day. The reaction mixture was extracted with diethyl ether twice, and the organic layer was washed with 1 M hydrochloric acid and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1/1 (v/v)) to give the title compound as a colorless oil (4.33 g, yield 90% (three steps)).

REFERENCE SYNTHETIC EXAMPLE 26 tert-Butyl 3-[methoxy(methyl)carbamoyl]methylpiperidinecarboxylate Diisobutylaluminum hydride (1.0 M solution in toluene, 23.4 mL, 23.7 mmol) was added dropwise to 3-methyl 1-tert-butyl 4-methylpiperidine-1,3-dicarboxylate (2.43 g, 9.46 mmol) in tetrahydrofuran (60 mL) cooled to -78°C, and the resulting reaction mixture was stirred at -78°C for 1 hour and at room temperature for 2 hours, then stirred with methanol and Celite at room temperature for 30 minutes and filtered. The filtrate was concentrated under reduced pressure. The resulting residue was roughly purified by silica gel column chromatography (hexane / ethyl acetate = 4/1 → 2/1 → 1/1 (v/v)) to give a colorless oil (1.62 g). The crude product (1.02 g) was dissolved in dichloromethane (30 mL) and stirred with 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol- 3(1H)-one (2.83 g, 6.67 mmol) at room temperature for 1.5 hours. After addition of a mixture (1/1 (v/v)) of saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium thiosulfate, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in t-butanol (12 mL), mixed with sodium dihydrogen phosphate (1.33 g, 11.1 mmol), water (12 mL) and 2-methyl butene (12 mL, 111 mmol) and stirred with sodium chlorite (1.68 g, 18.6 mmol) under cooling with ice for 30 minutes and then at room temperature 1 hour. After addition of saturated aqueous sodium thiosulfate, the reaction mixture was extracted with ethyl 40 acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in N,N- dimethylformamide (30 mL), mixed with N,O-dimethylhydroxylamine hydrochloride (396 mg, 4.06 mmol) and O-(7-azabenzotriazolyl)-N,N,N’,N’-tetramethyluronium hexafluorophosphate (2.00 g, 5.41 mmol) and stirred with N,N-diisopropylethylamine 45 (1.50 mL, 8.45 mmol) at room temperature for one day. After addition of water, the reaction solution was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 4/1 → 2/1 (v/v)) to give the title compound as a pale yellow oil (644 mg, yield 38% (four steps)).

REFERENCE SYNTHETIC EXAMPLE 27 tert-Butyl 4-methyl(7H-pyrrolo[2,3-d]pyrimidinecarbonyl)piperidinecarboxylate The reactions in Reference Synthetic Example 10 were carried out in substantially the same manners except that tert-butyl 3-[methoxy(methyl)carbamoyl] methylpiperidinecarboxylate was used instead of N-methoxy-N,2-dimethylbenzamide to give the title compound as a pale yellow solid (53.8 mg, yield 73%).

REFERENCE SYNTHETIC EXAMPLE 28 tert-Butyl 3-[methoxy(methyl)carbamoyl]piperidinecarboxylate The reactions in Reference Synthetic Example 9 were carried out in substantially the same manners except that 1-(tert-butoxycarbonyl)piperidinecarboxylic acid was used instead of 2-methylbenzoic acid to give the title compound as a colorless oil (1.68 g, yield 57%).

REFERENCE SYNTHETIC EXAMPLE 29 tert-Butyl 3-(7H-pyrrolo[2,3-d]pyrimidinecarbonyl) piperidine carboxylate The reactions in Reference Synthetic Example 10 were carried out in substantially the same manners except that tert-butyl 3- [methoxy(methyl)carbamoyl]piperidinecarboxylate was used instead of N-methoxy- N,2-dimethylbenzamide to give the title compound as a pale yellow solid (1.19 g, yield 68%).

REFERENCE SYNTHETIC EXAMPLE 30 1-[(Benzyloxy)carbonyl]piperidinecarboxylic acid Nipecotic acid (3.93 g, 30.4 mmol) and sodium carbonate (5.10 g, 48.1 mmol) in water (40 mL) was mixed with benzyl chloroformate (5.20 mL, 36.4 mmol) under cooling with ice and stirred at room temperature for one day. After addition of water and 1 M aqueous sodium hydroxide, the reaction mixture was allowed to separate by adding diethyl ether. The aqueous layer was adjusted to pH 1 with concentrated hydrochloric acid and extracted with ethyl acetate. The resulting organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give the title compound as a pale yellow oil (5.86 g, yield 73%).

REFERENCE SYNTHETIC EXAMPLE 31 Benzyl 3-[methoxy(methyl)carbamoyl]piperidinecarboxylate 1-[(Benzyloxy)carbonyl]piperidinecarboxylic acid (5.86 g, 22.3 mmol) and N,O- dimethylhydroxylamine hydrochloride (3.55 g, 36.4 mmol) in tetrahydrofuran (60 mL) was stirred with triethylamine (5.50 mL, 39.5 mmol), 1-hydroxybenzotriazole (1.17 g, 8.66 mmol) and 1-(3-dimethylaminopropyl)ethylcarbodiimide hydrochloride (7.18 g, 37.4 mmol) at room temperature for one day. After addition of water, the reaction 40 solution was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1/1 (v/v)) to give the title compound as a colorless oil (5.95 g, yield 87%). 45 REFERENCE SYNTHETIC EXAMPLE 32 Benzyl 3-(7H-pyrrolo[2,3-d]pyrimidinecarbonyl)piperidinecarboxylate The reactions in Reference Synthetic Example 10 were carried out in substantially the same manners except that benzyl 3- [methoxy(methyl)carbamoyl]piperidinecarboxylate was used instead of N-methoxy- N,2-dimethylbenzamide to give the title compound as a pale yellow solid (3.56 g, yield 53%).

REFERENCE SYNTHETIC EXAMPLE 33 1-Benzylpiperidinecarboxylic acid Nipecotic acid (1.31 g, 10.2 mmol), benzaldehyde (1.12 g, 10.6 mmol) and 5% palladium-carbon (0.18 g) in methanol (10 mL) was stirred at room temperature for one day under a hydrogen atmosphere. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in methanol (50 mL) was stirred with benzaldehyde (4.40 g, 41.5 mmol) and 5% palladium-carbon (0.118 g) at room temperature for one day. The reaction mixture was filtered, and the filtrated was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform / methanol = 10/1 → 5/1 (v/v)) to give the title compound as a colorless oil (1.41 g, yield 63%).

REFERENCE SYNTHETIC EXAMPLE 34 1-Benzyl-N-methoxy-N-methylpiperidinecarboxamide 1-Benzylpiperidinecarboxylic acid (318 mg, 1.45 mmol) and N,O- dimethylhydroxylamine hydrochloride (287 mg, 2.94 mmol) in tetrahydrofuran (5 mL) was stirred with triethylamine (283 µL, 2.03 mmol) , 1-hydroxybenzotriazole (101 mg, 0.747 mmol) and 1-(3-dimethylaminopropyl)ethylcarbodiimide hydrochloride (560 mg, 2.92 mmol) at room temperature for one day. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residues was purified by silica gel column chromatography (hexane / ethyl acetate = 1/1 (v/v)) to give the title compound as a colorless oil (272 mg, yield 71%).

REFERENCE SYNTHETIC EXAMPLE 35 (1-Benzylpiperidinyl)(7H-pyrrolo[2,3-d]pyrimidinyl)methanone The reactions in Reference Synthetic Example 10 were carried out in substantially the same manners except that 1-benzyl-N-methoxy-N-methylpiperidine carboxamide was used instead of N-methoxy-N,2-dimethylbenzamide to give the title compound as a yellow amorphous (121 mg, yield 91%).

REFERENCE SYNTHETIC EXAMPLE 36 Phenyl 1,3,4-thiadiazolylcarbamate 1,3,4-Thiadiazolamine (253 mg, 2.50 mmol) in dimethylacetamide (3 mL) was stirred with phenyl chloroformate (392 µL, 3.13. mmol) at room temperature for one day.

After addition of water, the precipitated solid was collected by filtration, washed with water and hexane and dried under reduced pressure to give the title compound as a 40 colorless solid (418 mg, yield 76%).

REFERENCE SYNTHETIC EXAMPLE 37 Phenyl (3-methylisothiazolyl)carbamate 3-Methylisothiazolamine (156 mg, 1.04 mmol) in pyridine (1.2 mL) was mixed with phenyl chloroformate (260 µL, 2.07 mmol) under cooling with ice and stirred at 45 room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure, and after addition of water, extracted with chloroform twice, and the organic layer was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1/1 (v/v)) to give the title compound as a pale yellow solid (173 mg, yield 71%).

REFERENCE SYNTHETIC EXAMPLE 38 tert-Butyl 4-[methoxy(methyl)carbamoyl]piperidinecarboxylate The reactions in Reference Synthetic Example 9 were carried out in substantially the same manners except that 1-(tert-butoxycarbonyl)piperidine-carboxylic acid was used instead of 2-methylbenzoic acid to give the title compound as a colorless oil (763 mg, yield 64%).

REFERENCE SYNTHETIC EXAMPLE 39 tert-Butyl 4-(7H-pyrrolo[2,3-d]pyrimidinecarbonyl)piperidinecarboxylate The reactions in Reference Synthetic Example 10 were carried out in substantially the same manners except that tert-butyl 4- [methoxy(methyl)carbamoyl]piperidinecarboxylate was used instead of N-methoxy- N,2-dimethylbenzamide to give the title compound as a pale yellow amorphous (486 mg, yield 74%).

REFERENCE SYNTHETIC EXAMPLE 40 N-Methoxy-N-methylpiperidinecarboxamide hydrochloride tert-Butyl 4-[methoxy(methyl)carbamoyl]piperidinecarboxylate (1.00 g, 3,67 mmol) obtained in Reference Synthetic Example 38 in 1,4-dioxane (10 mL) was stirred with 4 M hydrogen chloride - 1,4-dioxane solution (8 mL) at room temperature for one day. The solid precipitated in the reaction mixture was collected by filtration to give the title compound as a colorless solid (650 mg, yield 85%).

REFERENCE SYNTHETIC EXAMPLE 41 N-Methoxy-N-methyl(2,2,2-trifluoroethyl)piperidinecarboxamide N-Methoxy-N-methylpiperidinecarboxamide hydrochloride (600 mg, 2.88 mmol) in water (5 mL) was adjusted to pH 10 with 1 M aqueous sodium hydroxide and extracted with 1-butanol. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a colorless solid. The resulting solid (200 mg, 1.16 mmol) was dissolved in N,N-dimethylformamide (4 mL) and stirred with potassium carbonate (481 mg, 3.48 mmol) and 2,2,2-trifluoroethyl trifluoromethanesulfonate (335 µL, 2.32 mmol) at room temperature for one day. After addition of water and saturated aqueous sodium chloride, the reaction mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (methanol / chloroform = 1/19 → 1/9 (v/v)) to give the title compound as a colorless oil (190 mg, yield 26%).

REFERENCE SYNTHETIC EXAMPLE 42 (7H-Pyrrolo[2,3-d]pyrimidinyl)[1-(2,2,2-trifluoroethyl)piperidinyl]methanone The reactions in Reference Synthetic Example 10 were carried out in 40 substantially the same manners except that N-methoxy-N-methyl(2,2,2- trifluoroethyl)piperidinecarboxamide was used instead of N-methoxy-N,2- dimethylbenzamide to give the title compound as a colorless solid (100 mg, yield 43%).

REFERENCE SYNTHETIC EXAMPLE 43 Benzyl 4-[methoxy(methyl)carbamoyl]piperidinecarboxylate 45 Benzyl chloroformate (1.64 mL, 11.6 mmol) was gradually added dropwise to piperidinecarboxylic acid (1.00 g, 7.74 mmol) and sodium carbonate (1.64 g, 15.5 mmol) in water (20 mL) under cooling with ice, and the resulting reaction mixture was stirred for 2 hours. After addition of 1 M aqueous sodium hydroxide, the reaction mixture was allowed to separate by adding ethyl acetate. The resulting aqueous layer was adjusted to pH 4 with 1 M hydrochloric acid and extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a colorless oil. The oil was dissolved in chloroform (30 mL) and stirred with N,O-dimethylhydroxylamine hydrochloride (1.50 g, 15.4 mmol), 1-(3- dimethylaminopropyl)ethylcarbodiimide hydrochloride (3.00 g, 15.4 mmol), 1- hydroxybenzotriazole (2.00 g, 15.4 mmol) and triethylamine (3.2 mL, 23.1 mmol) at room temperature for 3 days. After addition of water and saturated aqueous ammonium chloride, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1/1 (v/v)) to give the title compound as a colorless oil (1.57 g, yield 66%).

REFERENCE SYNTHETIC EXAMPLE 44 Benzyl 4-(7H-pyrrolo[2,3-d]pyrimidinecarbonyl)piperidinecarboxylate The reactions in Reference Synthetic Example 10 were carried out in substantially the same manners except that benzyl 4- [methoxy(methyl)carbamoyl]piperidinecarboxylate was used instead of N-methoxy- N,2-dimethylbenzamide to give the title compound as a yellow oil (1.40 g, yield 78%).

REFERENCE SYNTHETIC EXAMPLE 45 tert-Butyl {trans[methoxy(methyl)carbamoyl]cyclohexyl}carbamate transAminocyclohexanecarboxylic acid (500 mg, 3.49 mmol) in water (10 mL) was stirred with di-tert-butyl bicarbonate (1.50 g, 6.98 mmol) and sodium hydroxide (280 mg, 6.98 mmol) at room temperature for 2 hours. The reaction mixture was washed with ethyl acetate, and the aqueous layer was adjusted to pH 3 with 1 M hydrochloric acid and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a colorless oil. The oil was dissolved in chloroform (10 mL) and stirred with N,O-dimethylhydroxylamine hydrochloride (683 mg, 7.00 mmol), 1-(3-dimethylaminopropyl)ethylcarbodiimide hydrochloride (1.34 g, 7.00 mmol), 1-hydroxybenzotriazole (946 mg, 7.00 mmol) and triethylamine (1.50 mL, 10.5 mmol) at room temperature for one day. After addition of water and saturated aqueous sodium chloride, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 2/1 → 1/1 (v/v)) to give the title compound as a colorless solid (513 mg, yield 51%).

REFERENCE SYNTHETIC EXAMPLE 46 tert-Butyl [trans(7H-pyrrolo[2,3-d]pyrimidinecarbonyl)cyclohexyl]carbamate The reactions in Reference Synthetic Example 10 were carried out in 40 substantially the same manners except that tert-butyl {trans [methoxy(methyl)carbamoyl]cyclohexyl}carbamate was used instead of N-methoxy-N,2- dimethylbenzamide to give the title compound as a colorless solid (52.0 mg, yield 8.4%).

REFERENCE SYNTHETIC EXAMPLE 47 Benzyl {trans[methoxy(methyl)carbamoyl]cyclohexyl}carbamate 45 Benzyl chloroformate (885 µL, 6.30 mmol) was gradually added dropwise to trans- 4-aminocyclohexanecarboxylic acid (600 mg, 4.20 mmol) and sodium carbonate (891 mg, 8.40 mmol) in water (12 mL) under cooling with ice, and the reaction mixture was stirred for one day. After addition of 1 M aqueous sodium hydroxide and ethyl acetate, the insoluble solid was collected by filtration to give a colorless solid. The solid was dissolved in chloroform (10 mL) and stirred with N,O-dimethylhydroxylamine hydrochloride (416 mg, 4.27 mmol), 1-(3-dimethylaminopropyl)ethylcarbodiimide hydrochloride (819 mg, 4.27 mmol), 1-hydroxybenzotriazole (577 mg, 4.27 mmol) and triethylamine (892 µL, 6.40 mmol) at room temperature for one day. After addition of water and saturated aqueous sodium chloride, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane / ethyl acetate = 2/1 (v/v)) to give the title compound as a colorless solid (350 mg, yield 26%).

REFERENCE SYNTHETIC EXAMPLE 48 Benzyl [trans(7H-pyrrolo[2,3-d]pyrimidinecarbonyl)cyclohexyl]carbamate The reactions in Reference Synthetic Example 10 were carried out in substantially the same manners except that benzyl {trans [methoxy(methyl)carbamoyl]cyclohexyl}carbamate was used instead of N-methoxy-N,2- dimethylbenzamide to give the title compound as a colorless solid (33.0 mg, yield 9.0%).

REFERENCE SYNTHETIC EXAMPLE 49 trans-N-Methoxy(methoxymethyl)-N-methylcyclohexanecarboxamide trans(Hydroxymethyl)-N-methoxy-N-methylcyclohexanecarboxamide (200 mg, 0.994 mmol) obtained in Reference Synthetic Example 21 in N,N-dimethylformamide (2 mL) was mixed with sodium hydride (55 wt% dispersion in mineral oil, 52.0 mg, 1.19 mmol) and methyl iodide (74.0 µL, 1.19 mmol) under cooling with ice and stirred for 1 hour while the temperature was gradually raised to room temperature. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1/2 → 1/1 (v/v)) to give the title compound as a colorless oil (197 mg, yield 92%).

REFERENCE SYNTHETIC EXAMPLE 50 [trans(Methoxymethyl)cyclohexyl](7H-pyrrolo[2,3-d]pyrimidinyl)methanone The reactions in Reference Synthetic Example 10 were carried out in substantially the same manners except that trans-N-methoxy(methoxymethyl)-N- methylcyclohexanecarboxamide was used instead of N-methoxy-N,2- dimethylbenzamide to give the title compound as an ivory solid (153 mg, yield 70%).

REFERENCE SYNTHETIC EXAMPLE 51 transHydroxy-N-methoxy-N-methylcyclohexanecarboxamide The reactions in Reference Synthetic Example 9 were carried out in substantially the same manners except that transhydroxycyclohexanecarboxylic acid was used 40 instead of 2-methylbenzoic acid to give the title compound as a colorless oil (1.89 g, yield 48%).

REFERENCE SYNTHETIC EXAMPLE 52 trans-N,4-Dimethoxy-N-methylcyclohexanecarboxamide transHydroxy-N-methoxy-N-methylcyclohexanecarboxamide (536 mg, 2.86 45 mmol) in N,N-dimethylformamide (5 mL) was mixed with sodium hydride (55 wt% dispersion in mineral oil, 150 mg, 3.44 mmol) and methyl iodide (214 µL, 3.44 mmol) under cooling with ice and stirred for 3 hours while the temperature was gradually raised to room temperature. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1/2 → 1/1 (v/v)) to give the title compound as a colorless oil (556 mg, yield 97%).

REFERENCE SYNTHETIC EXAMPLE 53 (transMethoxycyclohexyl)(7H-pyrrolo[2,3-d]pyrimidinyl)methanone The reactions in Reference Synthetic Example 10 were carried out in substantially the same manners except that trans-N,4-dimethoxy-N- methylcyclohexanecarboxamide was used instead of N-methoxy-N,2- dimethylbenzamide to give the title compound as an ivory solid (178 mg, yield 69%).

REFERENCE SYNTHETIC EXAMPLES 54 To 60 The reactions in Reference Synthetic Example 9 were carried out in substantially the same manners except that 4,4-difluoroxyclohexanecarboxylic acid, bicycle[2.2.1]heptanecarboxylic acid, cycloheptanecarboxylic acid, cyclobutanecarboxylic acid, cyclopentanecarboxylic acid, trans (trifluoromethyl)cyclohexanecarboxylic acid or cis (trifluoromethyl)cyclohexanecarboxylic acid was used instead of 2-methylbenzoic acid to give the compounds of Reference Synthetic Examples 54 to 60. The names, morphologies and yields of the compounds synthesized are shown in Table 5.

TABLE 5 REFERENCE SYNTHETIC EXAMPLES 61 TO 67 The reactions in Reference Synthetic Example 10 were carried out in substantially the same manners except that the compounds obtained in Reference Synthetic Examples 54 to 60 were used instead of N-methoxy-N,2-dimethylbenzamide to give the compounds of Reference Synthetic Examples 61 to 67. The names, morphologies and yields of the compounds synthesized are shown in Table 6.

TABLE 6 REFERENCE SYNTHETIC EXAMPLE 68 [trans(tert-Butyldiphenylsilyl)oxy]-N-methoxyl-N-methylcyclohexanecarboxamide transHydroxy-N-methoxy-N-methylcyclohexanecarboxamide (1.35 g, 7.21 mmol) obtained in Reference Synthetic Example 51 in N,N-dimethylformamide (48 mL) was stirred with imidazole (598 mg, 8.65 mmol) and tert-butylchlorodiphenylsilane (2.07 mL, 7.93 mmol) for 4 hours under cooling with ice. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 15/1 → 7/1 → 3/1 (v/v)) to give the title compound as a colorless oil (1.52 g, yield 50%).

REFERENCE SYNTHETIC EXAMPLE 69 {trans[(tert-Butyldiphenylsilyl)oxy]cyclohexyl}(7H-pyrrolo[2,3-d]pyrimidin yl)methanone The reactions in Reference Synthetic Example 10 were carried out in substantially the same manners except that trans[(tert-butyldiphenylsilyl)oxy]-N- methoxy-N-methylcyclohexanecarboxamide was used instead of N-methoxy-N,2- dimethylbenzamide to give the title compound as a yellow amorphous (1.34 g, yield 78%).

REFERENCE SYNTHETIC EXAMPLE 70 1-{4-[(tert-Butyldiphenylsilyl)oxy]cyclohexyl}-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5- c]pyrimidine The reactions in Synthetic Example 5 were carried out in substantially the same manners except that {trans[(tert-butyldiphenylsilyl)oxy]cyclohexyl}(7H-pyrrolo[2,3- d]pyrimidinyl)methanone was used instead of (7H-pyrrolo[2,3-d]pyrimidinyl)(o- tolyl)methanone to give the title compound as a pale yellow solid (838 mg, yield 61%).

REFERENCE SYNTHETIC EXAMPLE 71 4-Hydroxy-N-methoxy-N-methylcyclohexanecarboxamide 4-Hydroxycyclohexanecarboxylic acid (10.0 g, 69.4 mmol) and N,O- dimethylhydroxylamine hydrochloride (8.80 g, 90.2 mmol) in dichloromethane (500 mL) was stirred with 1-(3-dimethylaminopropyl)ethylcarbodiimide hydrochloride (17.3 g, 90.2 mmol), 1-hydroxybenzotriazole (12.2 g, 90.2 mmol) and N,N-diisopropylethylamine (24.2 mL, 139 mmol) at room temperature for one day. After addition of water, the reaction mixture was extracted with chloroform, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1/1 (v/v) → ethyl acetate) to give the title compound as a yellow oil (9.07 g, yield 70%).

REFERENCE SYNTHETIC EXAMPLE 72 4-[(tert-Butyldimethylsilyl)oxy]-N-methoxy-N-methylcyclohexanecarboxamide 4-Hydroxy-N-methoxy-N-methylcyclohexanecarboxamide (7.34 g, 39.2 mmol) in N,N-dimethylformamide (200 mL) was stirred with imidazole (4.80 g, 70.6 mmol) and tert-butylchlorodimethylsilane (7.70 g, 51.0 mmol) at room temperature for one day.

After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 25/1 → 4/1 (v/v)) to give the title compound as a colorless oil (8.68 g, yield 73%).

REFERENCE SYNTHETIC EXAMPLE 73 {4-[(tert-Butyldimethylsilyl)oxy]cyclohexyl}(7H-pyrrolo[2,3-d]pyrimidinyl)methanone The reactions in Reference Synthetic Example 10 were carried out in substantially the same manners except that 4-[(tert-butyldimethylsilyl)oxy]-N-methoxy- N-methylcyclohexanecarboxamide was used instead of N-methoxy-N,2- dimethylbenzamide to give the title compound as a pale yellow solid (7.14 g, yield 69%).

REFERENCE SYNTHETIC EXAMPLE 74 1-{4-[(tert-Butyldimethylsilyl)oxy]cyclohexyl}-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5- c]pyrimidine The reactions in Synthetic Example 5 were carried out in substantially the same manners except that {4-[(tert-butyldiphenylsilyl)oxy]cyclohexyl}(7H-pyrrolo[2,3- d]pyrimidinyl)methanone was used instead of (7H-pyrrolo[2,3-d]pyrimidinyl)(o- tolyl)methanone to give the title compound as a pale yellow solid (5.20 g, yield 70%).

REFERENCE SYNTHETIC EXAMPLE 75 4-(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexanol 1-{4-[(tert-Butyldimethylsilyl)oxy]cyclohexyl}-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5- c]pyrimidine (500 mg, 1.35 mmol) in a mixture of dichloromethane (5 mL) and methanol (5 mL) was stirred with pyridinium p-toluenesulfonate (338 mg, 1.35 mmol) at 60°C for 3 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane / ethyl acetate = 4/1 → 1/1 (v/v) → ethyl acetate) to give the title compound as a colorless solid (259 mg, yield 75%).

REFERENCE SYNTHETIC EXAMPLE 76 40 Benzyl 4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine carbonyl)piperidinecarboxylate The reactions in Reference Synthetic Example 18 were carried out in substantially the same manners except that benzyl 4- [methoxy(methyl)carbamoyl]piperidinecarboxylate obtained in Reference Synthetic 45 Example 43 was used instead of benzyl 3-[methoxy(methyl)carbamoyl]piperidine carboxylate to give the title compound as a yellow oil (49.6 mg, yield 71%).

REFERENCE SYNTHETIC EXAMPLE 77 Benzyl 4-[amino(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin yl)methyl]piperidinecarboxylate The reactions in Reference Synthetic Example 7 were carried out in substantially the same manners except that benzyl 4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H- pyrrolo[2,3-d]pyrimidinecarbonyl)piperidinecarboxylate was used instead of cyclohexyl(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin yl)methanone to give the title compound as a colorless oil (33.2 mg, yield 67%).

REFERENCE SYNTHETIC EXAMPLE 78 Benzyl 4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-imidazo[1,5-c]pyrrolo[3,2-e]pyrimidin yl)piperidinecarboxylate The reactions in Reference Synthetic Example 20 were carried out in substantially the same manners except that benzyl 4-[amino(7-{[2- (trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidinyl)methyl]piperidine carboxylate was used instead of benzyl 3-[amino(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H- pyrrolo[2,3-d]pyrimidinyl)methyl]piperidinecarboxylate to give a brown oily mixture containing the title compound (16.0 mg). The resulting mixture was used for the next step without purification.

REFERENCE SYNTHETIC EXAMPLE 79 Benzyl 4-[amino(7H-pyrrolo[2,3-d]pyrimidinyl)methyl]piperidinecarboxylate Benzyl 4-(7H-pyrrolo[2,3-d]pyrimidinecarbonyl)piperidinecarboxylate (50.0 mg, 0.137 mmol) obtained in Reference Synthetic Example 44 in methanol (1 mL) was stirred with aqueous hydroxylamine (300 µL) at 75°C for 4 hours and allowed to cool to room temperature. After addition of water and saturated aqueous ammonium chloride, the reaction mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a colorless oil. The oil was dissolved in methanol (3 mL), stirred with zinc powder (45.0 mg, 0.685 mmol) and acetic acid (24.0 µL, 0.411 mmol) at 75°C for 3 hours and allowed to cool to room temperature. After addition of water and saturated aqueous sodium hydrogen carbonate, the reaction mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the title compound as a yellow oil (50.0 mg, yield 99%).

REFERENCE SYNTHETIC EXAMPLE 80 Piperidinyl(7H-pyrrolo[2,3-d]pyrimidinyl)methanone hydrochloride tert-Butyl 4-(7H-pyrrolo[2,3-d]pyrimidinecarbonyl)piperidinecarboxylate (840 mg, 2.54 mmol) obtained in Reference Synthetic Example 39 in 1,4-dioxane (3 mL) was stirred with 4 M hydrogen chloride-1,4-dioxane (3 mL) at room temperature for one day. The resulting solid was collected by filtration to give the title compound as a brown solid (677 mg, yield 99%).

REFERENCE SYNTHETIC EXAMPLE 81 40 (7H-Pyrrolo[2,3-d]pyrimidinyl){1-[4-(trifluoromethyl)benzyl]piperidinyl}methanone Piperidinyl(7H-pyrrolo[2,3-d]pyrimidinyl)methanone hydrochloride (60.0 mg, 0.224 mmol) in acetonitrile (3 mL) was stirred with 4-(trifluoromethyl)benzyl bromide (70.0 mg, 0.292 mmol) and N,N-diisopropylethylamine (144 µL, 0.784 mmol) at 60°C for 2 hours and allowed to cool to room temperature. After addition of water and saturated 45 aqueous ammonium chloride, the reaction mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1/1 (v/v)) to give the title compound as a pale yellow solid (65.0 mg, yield 75%).

REFERENCE SYNTHETIC EXAMPLE 82 (7H-Pyrrolo[2,3-d]pyrimidinyl){1-[4-(trifluoromethyl)benzyl]piperidinyl}methanamine The reactions in Reference Synthetic Example 79 were carried out in substantially the same manners except that (7H-pyrrolo[2,3-d]pyrimidinyl){1-[4- (trifluoromethyl)benzyl]piperidinyl}methanone was used instead of benzyl 4-(7H- pyrrolo[2,3-d]pyrimidinecarbonyl)piperidinecarboxylate to give the title compound as a colorless solid (65.0 mg, yield 99%).

REFERENCE SYNTHETIC EXAMPLE 83 Benzyl 3-[methoxy(methyl)carbamoyl]azetidinecarboxylate The reactions in Reference Synthetic Example 43 were carried out in substantially the same manners except that azetidinecarboxylic acid was used instead of piperidinecarboxylic acid to give the title compound as a colorless oil (1.18 g, yield 21%).

REFERENCE SYNTHETIC EXAMPLE 84 Benzyl 3-(7H-pyrrolo[2,3-d]pyrimidinecarbonyl)azetidinecarboxylate The reactions in Reference Synthetic Example 10 were carried out in substantially the same manners except that benzyl 3- [methoxy(methyl)carbamoyl]azetidinecarboxylate was used instead of N-methoxy- N,2-dimethylbenzamide to give the title compound as a yellow solid (656 mg, yield 46%).

REFERENCE SYNTHETIC EXAMPLE 85 4-(Hydroxymethyl)-N-methoxy-N-methylbenzamide 4-(Hydroxymethyl)benzoic acid (3.00 g, 19.7 mmol) and N,O- dimethylhydroxylamine hydrochloride (2.31 g, 23.7 mmol) in chloroform (30 mL) was stirred with 1-(3-dimethylaminopropyl)ethylcarbodiimide hydrochloride (4.54 g, 23.7 mmol), 1-hydroxybenzotriazole (3.20 g, 23.7 mmol) and N,N-diisopropylethylamine (8.04 mL, 47.3 mmol) at room temperature for one day. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a mixture containing the title compound as a colorless oil (4.20 g). The resulting mixture was used for the next step.

REFERENCE SYNTHETIC EXAMPLE 86 4-{[(tert-Butyldimethylsilyl)oxy]methyl}-N-methoxy-N-methylbenzamide 4-(Hydroxymethyl)-N-methoxy-N-methylbenzamide (4.20 g) obtained in Reference Synthetic Example 85 in N,N-dimethylformamide (10 mL) was stirred with imidazole (4.00 g, 59.2 mmol) and tert-butylchlorodimethylsilane (3.60 g, 23.7 mmol) at room temperature for one day. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium 40 chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate =5/1 → 3/1 (v/v)) to give the title compound as a colorless oil (5.45 g, yield 89% (two steps)).

REFERENCE SYNTHETIC EXAMPLE 87 45 (4-{[(tert-Butyldimethylsilyl)oxy]methyl}phenyl)(7H-pyrrolo[2,3-d]pyrimidin yl)methanone The reactions in Reference Synthetic Example 10 were carried out in substantially the same manners except that 4-{[(tert-butyldimethylsilyl)oxy]methyl}-N- methoxy-N-methylbenzamide was used instead of N-methoxy-N,2-dimethylbenzamide to give the title compound as a pale yellow solid (4.40 g, yield 68%).

REFERENCE SYNTHETIC EXAMPLE 88 1-(4-{[(tert-Butyldimethylsilyl)oxy]methyl}phenyl)-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5- c]pyrimidine The reactions in Synthetic Example 5 were carried out in substantially the same manners except that (4-{[(tert-butyldimethylsilyl)oxy]methyl}phenyl)(7H-pyrrolo[2,3- d]pyrimidinyl)methanone was used instead of (7H-pyrrolo[2,3-d]pyrimidinyl)(o- tolyl)methanone to give the title compound as a colorless solid (3.58 g, yield 79%).

REFERENCE SYNTHETIC EXAMPLE 89 cis(Hydroxymethyl)-N-methoxy-N-methylcyclohexanecarboxamide The reactions in Reference Synthetic Example 85 were carried out in substantially the same manners except that cis (hydroxymethyl)cyclohexanecarboxylic acid was used instead of 4- (hydroxymethyl)benzoic acid to give a mixture containing the title compound as a colorless oil (3.17 g). The resulting mixture was used for the next step.

REFERENCE SYNTHETIC EXAMPLE 90 cis{[(tert-Butyldimethylsilyl)oxy]methyl}-N-methoxy-N- methylcyclohexanecarboxamide The reactions in Reference Synthetic Example 86 were carried out in substantially the same manners except that cis(hydroxymethyl)-N-methoxy-N- methylcyclohexanecarboxamide obtained in Reference Synthetic Example 89 was used instead of 4-(hydroxymethyl)-N-methoxy-N-methylbenzamide to give the title compound as a colorless oil (5.3 g, yield 89% (two steps)).

REFERENCE SYNTHETIC EXAMPLE 91 (cis{[(tert-Butyldimethylsilyl)oxy]methyl}cyclohexyl)(7H-pyrrolo[2,3-d]pyrimidin yl)methanone The reactions in Reference Synthetic Example 10 were carried out in substantially the same manners except that cis{[(tert-butyldimethylsilyl)oxy]methyl}- N-methoxy-N-methylcyclohexanecarboxamide was used instead of N-methoxy-N,2- dimethylbenzamide to give the title compound as a pale yellow solid (4.50 g, yield 72%).

REFERENCE SYNTHETIC EXAMPLE 92 1-(trans{[(tert-Butyldimethylsilyl)oxy]methyl}cyclohexyl)-7H-pyrrolo[3,2- e][1,2,3]triazolo[1,5-c]pyrimidine The reactions in Synthetic Example 5 were carried out in substantially the same manners except that (cis{[(tert-Butyldimethylsilyl)oxy]methyl}cyclohexyl)(7H- pyrrolo[2,3-d]pyrimidinyl)methanone was used instead of (7H-pyrrolo[2,3-d]pyrimidin- 4-yl)(o-tolyl)methanone to give the title compound as a pale yellow solid (3.49 g, yield 40 75%). (although the cis-isomer was used as the starting material, only the trans- isomer of the title compound was obtained.) REFERENCE SYNTHETIC EXAMPLE 93 -(Bromomethyl)thiophenecarbonitrile -Methylthiophenecarbonitrile (500 mg, 4.06 mmol) in carbon tetrachloride (10 45 mL) was stirred with N-bromosuccinimide (867 mg, 4.87 mmol) and 2,2’- azobis(isobutyronitrile) (133 mg, 0.810 mmol) at 60°C for 4.5 hours and allowed to cool to room temperature. After addition of saturated aqueous sodium thiosulfate, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 2/1 → 1/1 (v/v)) to give the title compound as a yellow oil (186 mg, yield 23%).

REFERENCE SYNTHETIC EXAMPLE 94 4-{[4-(7H-pyrrolo[2,3-d]pyrimidinecarbonyl)piperidinyl]methyl}benzonitrile The reactions in Reference Synthetic Example 81 were carried out in substantially the same manners except that 4-(bromomethyl)benzonitrile was used instead of 4-(trifluoromethyl)benzyl bromide to give the title compound as a pale yellow solid (150.9 mg, yield 65%).

REFERENCE SYNTHETIC EXAMPLE 95 4-{[4-(7-{[2-(Trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine carbonyl)piperidinyl]methyl}benzonitrile The reactions in Reference Synthetic Example 15 were carried out in substantially the same manners except that 4-{[4-(7H-pyrrolo[2,3-d]pyrimidine carbonyl)piperidinyl]methyl}benzonitrile was used instead of 4-iodo-7H-pyrrolo[2,3- d]pyrimidine to give the title compound as a yellow oil (124.1 mg, yield 75%).

REFERENCE SYNTHETIC EXAMPLE 96 4-({4-[Amino(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin yl)methyl]piperidinyl}methyl)benzonitrile The reactions in Reference Synthetic Example 7 were carried out in substantially the same manners except that 4-({4-[amino(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H- pyrrolo[2,3-d]pyrimidinyl)methyl]piperidinyl}methyl)benzonitrile was used instead of cyclohexyl(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin yl)methanone to give the title compound as a yellow oil (42.9 mg, yield 34%).

REFERENCE SYNTHETIC EXAMPLE 97 4-{[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-imidazo[1,5-c]pyrrolo[3,2-e]pyrimidin yl)piperidinyl]methyl}benzonitrile The reactions in Reference Synthetic Example 20 were carried out in substantially the same manners except that 4-({4-[amino(7-{[2- (trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidinyl)methyl]piperidin yl}methyl)benzonitrile was used instead of benzyl 3-[amino(7-{[2- (trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidinyl)methyl]piperidine carboxylate to give a brown oil containing the title compound (37.4 mg). The resulting mixture was used for the next step.

REFERENCE SYNTHETIC EXAMPLE 98 Benzyl 3-[methoxy(methyl)carbamoyl]pyrrolidinecarboxylate Triethylamine (1.68 mL, 12.0 mmol) was added dropwise to 1- [(benzyloxy)carbonyl]pyrrolidinecarboxylic acid (1.00 g, 4.01 mmol), N,O- 40 dimethylhydroxylamine hydrochloride (782 mg, 8.02 mmol), 1-(3-dimethylaminopropyl)- 3-ethylcarbodiimide hydrochloride (1.54 g, 8.02 mmol) and 1-hydroxybenzotriazole (1.08 g, 8.02 mmol) in chloroform (20 mL), and the reaction mixture was stirred at room temperature for 16 hours. After addition of water, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and 45 concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1/1 → 3/7 (v/v)) to give the title compound as a yellow oil (1.11 g, yield 95%).

REFERENCE SYNTHETIC EXAMPLE 99 Benzyl 3-(7H-pyrrolo[2,3-d]pyrimidinecarbonyl)pyrrolidinecarboxylate The reactions in Reference Synthetic Example 10 were carried out in substantially the same manners except that benzyl 3- [methoxy(methyl)carbamoyl]pyrrolidinecarboxylate was used instead of N-methoxy- N,2-dimethylbenzamide to give a pale yellow solid containing the title compound (216 mg). The resulting mixture was used for the next step.

REFERENCE SYNTHETIC EXAMPLE 100 3-Amino(4-chlorophenyl)-1,1,1-trifluoropropanol 1-(4-Chlorophenyl)-2,2,2-trifluoroethanone (2.00 g, 9.59 mmol) in nitromethane (10 mL) was stirred with potassium carbonate (1.32 g, 9.59 mmol) at room temperature for 1 hour. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue (pale yellow amorphous, 3.3 g) was dissolved in ethanol (52 mL), then 6 M hydrochloric acid was added dropwise under cooling with ice, and zinc powder (3.13 g, 48.0 mmol) was gradually added. The reaction mixture was stirred for one day while the temperature was gradually raised to room temperature, and filtered through Celite. The filtrate was concentrated under reduced pressure. The residue was mixed with 28 wt% aqueous ammonia and extracted with chloroform, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 3/1 → 1/1 (v/v)) to give the title compound as a colorless solid (609 mg, yield 26%).

REFERENCE SYNTHETIC EXAMPLE 101 3-Amino-1,1,1-trifluorophenylpropanol The reactions in Reference Synthetic Example 100 were carried out in substantially the same manners except that 2,2,2-trifluorophenylethanone was used instead of 1-(4-chlorophenyl)-2,2,2-trifluoroethanone to give the title compound as a colorless solid (54 mg, yield 46%).

REFERENCE SYNTHETIC EXAMPLE 102 3-Amino-1,1,1-trifluoro(4-fluorophenyl)propanol n-Butyllithium (2.66 M solution in hexane, 12.4 mL, 33.0 mmol) was added dropwise to 1-bromofluorobenzene (5.25 g, 30.0 mmol) in tetrahydrofuran (50 mL) cooled to -78°C, and the reaction mixture was stirred at -78°C for 30 minutes, mixed with ethyl 2,2,2-trifluoroacetate (4.64 mL, 45 mmol) at -78°C and then stirred for another minutes while the temperature was gradually raised to room temperature. The reaction mixture was stirred with nitromethane (3.25 mL, 60 mmol) at room temperature for 30 minutes. The resulting reaction mixture was added to 1 M hydrochloric acid (50 mL) and extracted with ethyl acetate. The organic layer was dried over anhydrous 40 sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 5/1 (v/v/)) to give a colorless oil. The colorless oil was dissolved in ethanol (25 mL) and stirred with 10% palladium- carbon (1 g) at room temperature for one day under a hydrogen atmosphere. The reaction mixture was filtered through Celite, and the filtrate was concentrated under 45 reduced pressure to give the title compound as a colorless solid (4.52 g, yield 68% (three steps)).

REFERENCE SYNTHETIC EXAMPLE 103 2-[4-(Trifluoromethyl)phenyl]oxirane Trimethylsulfonium iodide (4.08 g, 20.0 mmol) in dimethyl sulfoxide (15 mL) was stirred with sodium hydride (55 wt% dispersion in mineral oil, 873 mg, 20.0 mmol) at room temperature for 1 hour and then with 4-(trifluoromethyl)styrene (2.96 g, 17.0 mmol) in dimethyl sulfoxide (10 mL) at room temperature for 2 hours. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 9/1 (v/v)) to give the title compound as a colorless oil (2.59 g, yield 81%).

REFERENCE SYNTHETIC EXAMPLE 104 1-(Piperidinyl)-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine acetate % Palladium-carbon (0.87 g) was added to benzyl 4-(7H-pyrrolo[3,2- e][1,2,3]triazolo[1,5-c]pyrimidinyl)piperidinecarboxylate (4.88 g, 13.0 mmol) obtained in Synthetic Example 26 in a mixture of acetic acid (60 mL), water (6 mL) and ethanol (10 mL), and after then the reaction system was flushed with hydrogen, the reaction mixture was stirred at room temperature for one day and then filtered. The filtrate was concentrated, and the resulting yellow solid was washed with ethanol to give the title compound as a colorless solid ( 3.30 g, yield 84%).

REFERENCE SYNTHETIC EXAMPLE 105 2-(4-Formylphenoxy)acetonitrile 4-Hydroxybenzaldehyde (244 mg, 2.00 mmol) in N,N-dimethylformamide (5 mL) was mixed with sodium hydride (60 wt% dispersion in liquid paraffin, 120 mg, 3.00 mmol) and chloroacetonitrile (189 µL, 3.00 mmol) under cooling with ice and then stirred at 50°C for 3 hours. The reaction mixture was allowed to cool to room temperature and mixed with saturated aqueous ammonium chloride and extracted with ethyl acetate.

The organic layer was washed with 1M aqueous sodium hydroxide, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the title compound as a brown oil (128 mg, yield 40%).

REFERENCE SYNTHETIC EXAMPLE 106 4-(Bromomethyl)benzamide 4-(Bromomethyl)benzoic acid (300 mg, 1.40 mmol) in ethyl acetate (5 mL) was stirred with thionyl chloride (249 µL, 3.50 mmol) at 75°C for 9 hours. The reaction mixture was allowed to cool to room temperature and concentrated under reduced pressure. The residue was dissolved in dichloromethane (5 mL) and stirred with 28% ammonia aqueous solution (380 µL, 5.60 mmol) under cooling with ice for 80 minutes.

The reaction mixture was mixed with water, and the precipitate was collected by filtration, washed with dichloromethane to give the title compound as a colorless solid (274 mg, yield 91%).

REFERENCE SYNTHETIC EXAMPLE 107 40 5-(Bromomethyl)(trifluoromethyl)benzonitrile -Methyl(trifluoromethyl)benzonitrile (200 mg, 1.08 mmol) in 1,2-dichloroethane (3 mL) was stirred with N-bromosuccinimide (192 mg, 1.08 mmol) and azobisisobutyronitrile (36.1 mg, 0.22 mmol) at 80°C for 2 hours. The reaction mixture allowed to cool to room temperature and was concentrated under reduced pressure. 45 The residue was purified by silica gel column chromatography (hexane → ethyl acetate / hexane = 1/3 (v/v)) to give the title compound as a colorless solid (140 mg, yield 49%).

REFERENCE SYNTHETIC EXAMPLE 108 4-(Bromomethyl)phthalonitrile The reactions in Reference Synthetic Example 107 were carried out in substantially the same manners except that 4-methylphthalonitrile was used instead of -methyl(trifluoromethyl)benzonitrile to give the title compound as a colorless solid (163 mg, yield 52%).

REFERENCE SYNTHETIC EXAMPLE 109 4-(Bromomethyl)(trifluoromethyl)benzonitrile The reactions in Reference Synthetic Example 107 were carried out in substantially the same manners except that 4-methyl(trifluoromethyl)benzonitrile was used instead of 5-methyl(trifluoromethyl)benzonitrile to give the title compound as a colorless solid (177 mg, yield 62%).

REFERENCE SYNTHETIC EXAMPLE 110 tert-Butyl 4-cyanophenethylcarbamate 2-(4-Bromophenyl)ethylamine (2.00 g, 10.0 mmol) in tetrahydrofuran (5 mL) was mixed with Di-tert-butyl dicarbonate (2.20 g, 10.0 mmol) under cooling with ice and then stirred at room temperature for one day. After addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue (900 mg) was dissolved in N,N-dimethylformamide (30 mL) and mixed with zinc cyanide (705 mg, 60.0 mmol) and tetrakis(triphenylphosphine)palladium(0) (347 mg, 0.300 mmol), and the reaction mixture was stirred at 150°C for 20 minutes under microwave irradiation. The resulting reaction mixture was allowed to cool to room temperature, mixed with saturated aqueous ammonium chloride and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 10/1 → 4/1 (v/v)) to give the title compound as a pale yellow solid (305 mg, yield 41%).

REFERENCE SYNTHETIC EXAMPLE 111 4-(2-Aminoethyl)benzonitrile tert-Butyl 4-cyanophenethylcarbamate (305 mg, 1.24 mmol) in dichloromethane (4 mL) was mixed with trifluoroacetic acid (3.50 mL, 47.1 mmol) under cooling with ice and then stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure, mixed with saturated aqueous potassium carbonate and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the title compound as a pale orange solid (72.5 mg, yield 40%).

REFERENCE SYNTHETIC EXAMPLE 112 tert-Butyl 3-oxoazetidinecarboxylate 40 tert-Butyl 3-hydroxyazetidinecarboxylate (4.02 g, 23.2 mmol) in dichloromethane (305 mL) was mixed with Dess-Martin Periodinane (9.55 g, 22.5 mmol) under cooling with ice and then stirred at room temperature for 3 hours. After addition of 10% aqueous sodium thiosulfate and saturated aqueous sodium hydrogen carbonate under cooling with ice, the reaction mixture was extracted with chloroform, and the 45 organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 2/1 (v/v)) to give the title compound as a colorless solid (3.39 g, yield 85%).

REFERENCE SYNTHETIC EXAMPLE 113 tert-Butyl 3-hydroxymethylazetidinecarboxylate Methylmagnesium bromide - tetrahydrofuran solution (1.12 M, 3.90 mL, 4.38 mmol) was added dropwise to tert-butyl 3-oxoazetidinecarboxylate (500 mg, 2.92 mmol) in tetrahydrofuran (5 mL) under cooling with ice and stirred for 90 minutes. After addition of saturated aqueous ammonium chloride, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 2/1 → 1/1 (v/v)) to give the title compound as a colorless solid (224 mg, yield 41%).

REFERENCE SYNTHETIC EXAMPLE 114 3-Methylazetidinol hydrochloride tert-Butyl 3-hydroxymethylazetidinecarboxylate (224 mg, 1.20 mmol) in ethyl acetate (1 mL) was mixed with 4 M hydrogen chloride - 1,4-dioxane solution (3.0 mL) under cooling with ice and then stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure to give a mixture containing the title compound (colorless oil, 162 mg). The mixture was used for the next step without further purification.

REFERENCE SYNTHETIC EXAMPLE 115 3-(Trifluoromethyl)azetidinol hydrochloride tert-Butyl 3-oxoazetidinecarboxylate (500 mg, 2.92 mmol) obtained in Reference Synthetic Example 112 and (trifluoromethyl)trimethylsilane (0.648 mL, 4.38 mmol) in tetrahydrofuran (10 mL) were mixed with tetrabutylammonium fluoride - tetrahydrofuran solution (1 M, 0.291 mL, 0.291 mmol) under cooling with ice and then stirred at room temperature for 1 hour. After addition of saturated aqueous ammonium chloride, the reaction mixture was extracted with diethyl ether, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure.

The residue was mixed with ethyl acetate (5 mL) and 1M aqueous citric acid (5 mL) and stirred at room temperature for 1 hour. After addition of water, the reaction mixture was extracted with diethyl ether. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in ethyl acetate (1.0 mL), mixed with 4 M hydrogen chloride - 1,4-dioxane solution (4 mL) under cooling with ice and then stirred at room temperature for 22 hours. The reaction mixture was concentrated under reduced pressure, and the precipitate was washed with ethyl acetate to give the title compound as a white solid (340 mg, yield 66% (2 steps)).

REFERENCE SYNTHETIC EXAMPLE 116 tert-Butyl 3-(2,2,2-trifluoroethoxy)azetidinecarboxylate 40 Sodium hydride (60 wt% dispersion in liquid paraffin, 151 mg, 3.46 mmol) in N,N- dimethylformamide (5 mL) was mixed with tert-butyl 3-hydroxyazetidinecarboxylate (500 mg, 2.89 mmol) in N,N-dimethylformamide (3 mL) under cooling with ice and stirred for 30 minutes, and the resulting reaction mixture was mixed with 2,2,2- trifluoroethyl trifluoromethanesulfonate (0.499 mL, 3.46 mmol) under cooling with ice 45 and then stirred at room temperature for 5 hours. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 3/1 → 1/1 (v/v)) to give the title compound as a colorless solid (350 mg, yield 48%).

REFERENCE SYNTHETIC EXAMPLE 117 3-(2,2,2-Trifluoroethoxy)azetidine hydrochloride tert-Butyl 3-(2,2,2-trifluoroethoxy)azetidinecarboxylate (350 mg, 1.37 mmol) in ethyl acetate (1.0 mL) was mixed with 4 M hydrogen chloride - 1,4-dioxane solution (3.0 mL) under cooling with ice and then stirred at room temperature for 2 hours. The reaction mixture was concentrated to give a mixture containing the title compound as a colorless oil (224 mg). The mixture was used for next step without further purification.

REFERENCE SYNTHETIC EXAMPLE 118 3-Amino-1,1,1-trifluoro(pyridinyl)propanol Isopropylmagnesium chloride-lithium chloride complex - tetrahydrofuran solution (1.3 M, 20.7 mL, 27.0 mmol) was added dropwise to 5-bromochloropyridine (5.20 g, 27.0 mmol) in tetrahydrofuran (40 mL) under cooling with ice, and the reaction mixture was stirred for 30 minutes and then mixed with ethyl 2,2,2-trifluoroacetate (11.5 g, 81.0 mmol) under cooling with ice and stirred at room temperature for 10 minutes. After addition of 1M hydrochloric acid, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a yellow oil. The yellow oil was dissolved in nitromethane (30 mL) and stirred with potassium carbonate (3.73 g, 27.0 mmol) at room temperature for minutes. The reaction mixture was added to 1M hydrochloric acid and extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 3/1 (v/v)) to give a yellow oil. The yellow oil was dissolved in tetrahydrofuran (20 mL), mixed with 10% palladium-carbon (600 mg) and triethylamine (2.60 mL, 18.7 mmol) and then stirred at room temperature for one day under a hydrogen atmosphere. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate → ethyl acetate / methanol / triethylamine = 9/1/1 (v/v/v)) to give the title compound as a colorless solid (913 mg, yield 31%(4 steps)).

REFERENCE SYNTHETIC EXAMPLE 119 3-Amino-1,1,1-trifluoro[4-(methylthio)phenyl]propanol The reactions in Reference Synthetic Example 102 were carried out in substantially the same manners except that (4-bromophenyl)(methyl)sulfane was used instead of 1-bromofluorobenzene to give the title compound as a colorless solid (2.61 g, yield 64%).

REFERENCE SYNTHETIC EXAMPLE 120 40 3-Amino-1,1,1-trifluoro(6-methoxypyridinyl)propanol The reactions in Reference Synthetic Example 102 were carried out in substantially the same manners except that 5-bromomethoxypyridine was used instead of 1-bromofluorobenzene to give the title compound as a colorless solid (1.52 g, yield 76%). 45 REFERENCE SYNTHETIC EXAMPLE 121 3-Amino-1,1,1-trifluoro(4-methoxyphenyl)propanol The reactions in Reference Synthetic Example 100 were carried out in substantially the same manners except that 2,2,2-trifluoro(4-methoxyphenyl)etanone was used instead of 1-(4-Chlorophenyl)-2,2,2-trifluoroethanone to give the title compound as a colorless solid (823 mg, yield 36%).

REFERENCE SYNTHETIC EXAMPLE 122 3-Amino(3,4-dimethoxyphenyl)-1,1,1-trifluoropropanol The reactions in Synthetic Example 100 were carried out in substantially the same manners except that 1-(3,4-dimethoxyphenyl)-2,2,2-trifluoroetanone was used instead of 1-(4-Chlorophenyl)-2,2,2-trifluoroethanone to give the title compound as a colorless solid (532 mg, yield 39%).

REFERENCE SYNTHETIC EXAMPLE 123 Ethyl (E)(4-fluorophenyl)acrylate 4-Fluorobenzaldehyde (9.61 g, 80.0 mmol) in tetrahydrofuran (120 mL) was mixed with ethyl 2-(diethoxyphosphoryl)acetate (17.9 g, 80.0 mmol) under cooling with ice, and then sodium ethoxide - ethanol solution (21 wt%, 44.8 mL, 120 mmol) was added dropwise to the reaction mixture under cooling with ice, and the resulting reaction mixture was stirred at room temperature for 2 hours. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 20/1 → 10/1 (v/v)) to give the title compound as a colorless oil (14.1 g, yield 91%).

REFERENCE SYNTHETIC EXAMPLE 124 trans-Ethyl 2-(4-fluorophenyl)cyclopropanecarboxylate Trimethylsulfoxonium iodide (7.92 g, 36.0 mmol) in dimethyl sulfoxide (40 mL) was mixed with sodium hydride (55 wt% dispersion in mineral oil, 1.57 g, 36.0 mmol) under cooling with ice, stirred at room temperature for 1 hour and then stirred with (E)-ethyl 3- (4-fluorophenyl)acrylate (5.83 g, 30.0 mmol) for 18 hours. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 10/1) to give the title compound as a colorless oil (793 mg, yield 13%).

REFERENCE SYNTHETIC EXAMPLE 125 2-{[trans(4-Fluorophenyl)cyclopropyl]methyl}isoindoline-1,3-dione trans-Ethyl 2-(4-Fluorophenyl)cyclopropanecarboxylate (793 mg, 4.57 mmol) in tetrahydrofuran (7 mL) was stirred with lithium aluminium hydride (173 mg, 4.57 mmol) under cooling with ice for 10 minutes. After addition of 1 M aqueous sodium hydroxide, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in tetrahydrofuran (10 mL), mixed with triphenylphosphine (999 mg, 3.81 mmol), isoindoline-1,3-dione (560 mg, 3.81 mmol) 40 and azodicarboxylic acid diisopropyl ester - toluene solution (1.9 M, 2.00 mL, 3.81 mmol) under cooling with ice, and the reaction mixture was stirred at room temperature for 1 hour and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 5/1 (v/v)) to give the title compound as a colorless solid (975 mg, yield 87%(2 steps)). 45 REFERENCE SYNTHETIC EXAMPLE 126 [trans(4-Fluorophenyl)cyclopropyl]methanamine 2-{[trans(4-Fluorophenyl)cyclopropyl]methyl}isoindoline-1,3-dione (974 mg, 3.30 mmol) in ethanol (50 mL) was stirred with hydrazine monohydrate (825 mg, 16.5 mmol) at 100°C for 30 minutes. The reaction mixture was concentrated to give the title compound as a colorless oil (360 mg, yield 66%).

REFERENCE SYNTHETIC EXAMPLE 127 4-Aminoadamantanol Concentrated sulfuric acid (35 mL) was mixed with concentrated nitric acid (4.5 mL) and 2-adamanthylamine (5.10 g, 4.57 mmol) under cooling with ice, and the reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was added to ice water and adjusted to pH 10 with 7.5 M aqueous sodium hydroxide.

After addition of water, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give the title compound as a yellow solid (2.79 g, yield 61%).

REFERENCE SYNTHETIC EXAMPLE 128 128a: Benzyl [(1R,2s,3S,5s,7s)hydroxyadamantanyl]carbamate 128b: Benzyl [(1R,2r,3S,5s,7s)hydroxyadamantanyl]carbamate 4-Aminoadamantanol (2.57 g, 15.4 mmol) in tetrahydrofuran (25 mL) was mixed with benzyl chloroformate (2.30 mL, 16.1 mmol) and 1 M aqueous sodium hydroxide (16.0 mL, 16.0 mmol) under cooling with ice and then stirred at room temperature for one day. After addition of 10% aqueous potassium hydrogen sulfate, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1/2 (v/v)) to give benzyl [(1R,2s3S,5s,7s) hydroxyadamantanyl]carbamate (Reference Synthetic Example 128a; yellow oil, 1.72 g, yield 37%) in a more polar fraction and benzyl [(1R,2r,3S,5s,7s) hydroxyadamantanyl]carbamate (Reference Synthetic Example 128b; yellow oil, 2.24 g, yield 48%) in a less polar fraction.

REFERENCE SYNTHETIC EXAMPLE 129 (1s,3R,4s,5S,7s)Aminoadamantanol Benzyl [(1R,2s,3S,5s,7s)hydroxyadamantanyl]carbamate (318 mg, 1.05 mmol) obtained in Reference Synthetic Example 128a and 5% palladium-carbon (63 mg) in methanol (2 mL) were stirred at room temperature for one day under a hydrogen atmosphere. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give the title compound as a colorless solid (144 mg, yield 82%).

REFERENCE SYNTHETIC EXAMPLE 130 (1s,3R,4r,5S,7s)Aminoadamantanol Benzyl [(1R,2r,3S,5s,7s)hydroxyadamantanyl]carbamate (2.24 g, 7.46 mmol) obtained in Reference Synthetic Example 128b and 5% palladium-carbon (700 mg) in methanol (30 mL) were stirred at room temperature for one day under a hydrogen 40 atmosphere. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give the title compound as a colorless solid (1.29 g, quantitative yield).

REFERENCE SYNTHETIC EXAMPLE 131 2-Bromo-2,2-difluoroethanamine hydrochloride 45 Borane tetrahydrofuran complex - tetrahydrofuran solution (1.06 M, 12.0 mL, 12.6 mmol) was added dropwise to 2-bromo-2,2-difluoroacetamide (2.00 g, 11.5 mmol) in tetrahydrofuran (20 mL) under cooling with ice, and the resulting reaction mixture was stirred at room temperature for 5 hours. After addition of ethanol (10 mL) and concentrated hydrochloric acid (7 mL), the reaction mixture was concentrated under reduced pressure. The precipitate was collected by filtration to give the title compound as a colorless solid (1.60 g, yield 71%).

REFERENCE SYNTHETIC EXAMPLE 132 4-Cyanophenethyl 4-methylbenzenesulfonate 4-(2-Hydroxyethyl)benzonitrile (200 mg, 1.35 mmol) in tetrahydrofuran (4 mL) was mixed with 4-methylbenzenesulfonyl chloride (389 mg, 2.04 mmol) and triethylamine (569 µL, 4.08 mmol) and stirred at room temperature for 1 day. After addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 9/1 → 3/1 → 1/1 (v/v)) to give the title compound as a colorless solid (174 mg, yield 43%).

REFERENCE SYNTHETIC EXAMPLE 133 4-{[(tert-Butyldimethylsilyl)oxy]methyl}-N-methoxy-N-methylcyclohexanecarboxamide 4-(Hydroxymethyl)cyclohexanecarboxic acid (25.0 g, 158 mmol) and N,O- dimethylhydroxylamine hydrochloride (23.1 g, 237 mmol) in chloroform (100 mL) were mixed with 1-(3-Dimethylaminopropyl)ethylcarbodiimide hydrochloride (36.4 g, 190 mmol), 1-hydroxybenzotriazole (5.00 g, 37.0 mmol) and N,N-diisopropylethylamine (41.3 mL, 237 mmol) and stirred at room temperature for 1 day. After addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was dissolved in N,N-dimethylformamide (100 mL) and mixed with imidazole (21.5 g, 316 mmol) and tert-butylchlorodimethylsilane (26.2 g, 174 mmol). The reaction mixture was stirred at room temperature for 1 day.

After addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 5/1 → 3/1 (v/v)) to give the title compound as a colorless oil (32.4 g, yield 65%).

REFERENCE SYNTHETIC EXAMPLE 134 (4-{[(tert-Butyldimethylsilyl)oxy]methyl}cyclohexyl)(7H-pyrrolo[2,3-d]pyrimidin yl)methanone Isopropylmagnesium chloride-lithium chloride complex - tetrahydrofuran solution (1.3 M, 39.2 mL, 51.0 mmol) was added dropwise to 4-iodo-7H-pyrrolo[2,3-d]pyrimidine (5.00 g, 20.4 mmol) obtained in Reference Synthetic Example 1 in tetrahydrofuran (50 mL) at -50°C, and stirred at -50°C for 1 hour. The reaction mixture was mixed with 4- {[(tert-butyldimethylsilyl)oxy]methyl}-N-methoxy-N-methylcyclohexanecarboxamide (6.44 g, 20.4 mmol) in tetrahydrofuran (30 mL) at -50°C and then stirred at room 40 temperature for 23 hours. After addition of saturated aqueous ammonium chloride, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 3/1 (v/v)) to give the title compound as a colorless oil (5.14 g, 45 yield 67%).

REFERENCE SYNTHETIC EXAMPLE 135 135a: 1-(cis{[(tert-Butyldimethylsilyl)oxy]methyl}cyclohexyl)-7H-pyrrolo[3,2- e][1,2,3]triazolo[1,5-c]pyrimidine 135b: 1-(trans{[(tert-Butyldimethylsilyl)oxy]methyl}cyclohexyl)-7H-pyrrolo[3,2- e][1,2,3]triazolo[1,5-c]pyrimidine (4-{[(tert-Butyldimethylsilyl)oxy]methyl}cyclohexyl)(7H-pyrrolo[2,3-d]pyrimidin yl)methanone (9.23 g, 24.7 mmol) in methanol (200 mL) was mixed with hydrazine monohydrate (38.0 mL, 618 mmol) and then stirred at 80°C for 3 hours. The reaction mixture was allowed to cool to room temperature and mixed with ethyl acetate, washed with water and saturated sodium chloride. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was dissolved in chloroform (240 mL) and mixed with manganese(IV) oxide (10.7 g, 124 mmol). The reaction mixture was stirred at 70°C for 1 day. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane / ethyl acetate = 3/1 (v/v)) to give 1-(cis{[(tert- butyldimethylsilyl)oxy]methyl}cyclohexyl)-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5- c]pyrimidine (Reference Synthetic Example 135a; pale yellow solid, 670 mg, yield 7%) in a less polar fraction and 1-(trans{[(tert-butyldimethylsilyl)oxy]methyl}cyclohexyl)- 7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine (Reference Synthetic Example 135b; pale yellow solid, 5.02 g, yield 52%) in a more polar fraction.

REFERENCE SYNTHETIC EXAMPLE 136 Cyclopropylamine hydrochloride Cyclopropylamine (0.600 mL, 8.76 mmol) was mixed with 1 M hydrogen chloride - diethylether solution (10 mL) under cooling with ice and stirred for 2 hours. The reaction mixture was concentrated under reduced pressure, and the precipitate was washed with diethyl ether to give the title compound as a colorless solid (686 mg, yield 84%).

REFERENCE SYNTHETIC EXAMPLE 137 tert-Butyl 3-(dimethylamino)azetidinecarboxylate tert-Butyl 3-oxoazetidinecarboxylate (300 mg, 1.75 mmol) obtained in Reference Synthetic Example 112 in methanol (15 mL) was mixed with acetic acid (1.0 mL), dimethylamine - tetrahydrofuran solution (2.0M, 1.31 mL, 2.63 mmol) and 2- picoline borane (280 mg, 2.63 mmol). The reaction mixture was stirred at room temperature for 1 day. After addition of 1M aqueous hydrogen chloride, the reaction mixture was extracted with ethyl acetate. The aqueous layer was adjusted to pH 10 with 1 M aqueous sodium hydroxide and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the title compound as a colorless solid (134 mg, yield 90%).

REFERENCE SYNTHETIC EXAMPLE 138 tert-Butyl 3-[ethyl(methyl)amino]azetidinecarboxylate The reactions in Reference Synthetic Example 137 were carried out in 40 substantially the same manners except that N-methylethanamine hydrochloride was used instead of dimethylamine - tetrahydrofuran solution to give the title compound as a pale yellow oil (121 mg, yield 46%).

REFERENCE SYNTHETIC EXAMPLE 139 tert-Butyl 3-(cyanomethylene)azetidinecarboxylate 45 Potassium tert-butoxide (2.03 g, 21.1 mmol) in tetrahydrofuran (20 mL) was mixed with diethyl cyanomethylphosphonate (3.54 g, 20.0 mmol) in tetrahydrofuran (20 mL) under cooling with ice and stirred for 30 minutes. The reaction mixture was mixed with tert-butyl 3-oxoazetidinecarboxylate (2.96 g, 17.3 mmol) obtained in Reference Synthetic Example 112 in tetrahydrofuran (20 mL) under cooling with ice and then stirred at room temperature for 1 day. After addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 3/1 (v/v)) to give the title compound as a colorless solid (1.93 g, yield 58%).

REFERENCE SYNTHETIC EXAMPLE 140 3-Hydroxy-N-methoxy-N-methyladamantanecarboxamide 3-Hydroxyadamantanecarboxylic acid (500 mg, 2.55 mmol) in dichloromethane (15 mL) was mixed with 1-(3-dimethylaminopropyl)ethylcarbodiimide hydrochloride (587 mg, 3.06 mmol), 1-hydroxybenzotriazole (103 mg, 0.765 mmol), N,O- dimethylhydroxylamine hydrochloride (298 mg, 3.06 mmol) and N,N- diisopropylethylamine (1.06 mL, 6.12 mmol) and then stirred at 40°C for 1 hours. The reaction mixture was stirred with 4-dimethylaminopyridine (779 mg, 6.38 mmol) at 40°C for 2 hours. After addition of saturated aqueous ammonium chloride, the reaction mixture was extracted with chloroform. The organic layer was washed with 1M hydrochloric acid and saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the title compound as a yellow oil (248 mg, yield 41%).

REFERENCE SYNTHETIC EXAMPLE 141 3-Hydroxyadamantanyl)(7H-pyrrolo[2,3-d]pyrimidinyl)methanone Isopropylmagnesium chloride - tetrahydrofuran solution (2.0 M, 0.518 mL, 1.035 mmol) was gradually added dropwise to 4-iodo-7H-pyrrolo[2,3-d]pyrimidine (56.4 mg, 0.230 mmol) in tetrahydrofuran (1 mL) cooled to -78°C, and the resulting reaction mixture was stirred at -78°C for 15 minutes. The reaction mixture was mixed with (2,6- dimethylphenyl)magnesium bromide - tetrahydrofuran solution (1.0 M, 0.575 mL, 0.575 mmol) and 3-hydroxy-N-methoxy-N-methyladamantanecarboxamide (55.1 mg, 0.23 mmol) in tetrahydrofuran (1 mL) and then stirred at room temperature for 1 day. After addition of saturated aqueous ammonium chloride, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (ethyl acetate) to give the title compound as a pale yellow solid (22.5 mg, yield 33%).

SYNTHETIC EXAMPLE 1 1-Cyclohexylmethyl-7H-imidazo[1,5-c]pyrrolo[3,2-e]pyrimidine Cyclohexyl[7-(triisopropylsilyl)-7H-pyrrolo[2,3-d]pyrimidinyl]methanone (48.2 mg, 0.120 mmol) obtained in Reference Synthetic Example 4 in acetic acid (1.2 mL) was 40 stirred with ammonium acetate (46.2 mg, 0.600 mmol) and acetaldehyde (purity 90%, µl, 0.24 mmol) at 110°C for 2.5 hours, and the reaction mixture was allowed to cool to room temperature, basified with saturated aqueous sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica 45 gel thin layer chromatography (NH-PLC05 plate manufactured by Fuji Silysia Chemical Ltd.: ethyl acetate) and further purified under the same conditions to give the title compound as a brown solid (12.4 mg, yield 41%).

SYNTHETIC EXAMPLE 2 1-Cyclohexyl-7H-imidazo[1,5-c]pyrrolo[3,2-e]pyrimidine Cyclohexyl[7-(triisopropylsilyl)-7H-pyrrolo[2,3-d]pyrimidinyl]methanone (52.5 mg, 0.136 mmol) obtained in Reference Synthetic Example 4 in formamide (2 mL) was stirred with formic acid (0.4 mL) at 170°C for 2 hours. The reaction mixture was allowed to cool to room temperature, and after dropwise addition of water, basified with M aqueous sodium hydroxide and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure.

The residue was stirred with phosphorus oxychloride (2 mL) at 110°C for 4 hours. The reaction mixture was allowed to cool to room temperature, and after dropwise addition of water, basified with 10 M aqueous sodium hydroxide and extracted with ethyl acetate.

The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Hi Flash column amino type manufactured by Yamazen Corporation: chloroform / methanol = 7/1 (v/v)) and further purified by silica gel thin layer chromatography (NH- PLC05 plate manufactured by Fuji Silysia Chemical Ltd.: ethyl acetate) to give the title compound as a brown solid (2.29 mg. yield 7%).

SYNTHETIC EXAMPLE 3 Benzyl 3-(7H-imidazo[1,5-c]pyrrolo[3,2-e]pyrimidinyl)piperidinecarboxylate Benzyl 3-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-imidazo[1,5-c]pyrrolo[3,2- e]pyrimidinyl)piperidinecarboxylate obtained in Reference Synthetic Example 20 in dichloromethane (1 mL) was stirred with trifluoroacetic acid (0.5 mL) at room temperature for 1.5 hours. The reaction mixture was concentrated under reduced pressure and azeotropically distilled with toluene. The resulting residue was dissolved in a mixture of dichloromethane (1 mL) and methanol (0.5 mL) and stirred with ethylenediamine (50 µL, 0.75 mmol) and 1 M aqueous sodium hydroxide (0.5 mL, 0.5 mmol) at room temperature for one day. The reaction mixture was diluted with ethyl acetate and washed with saturated aqueous ammonium chloride and saturated aqueous sodium chloride, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Hi Flash column amino type manufactured by Yamazen Corporation: chloroform / methanol = 10/1 → 5/1 (v/v)) to give the title compound as a pale yellow oil (17.3 mg, yield 52%).

SYNTHETIC EXAMPLE 4 3-[3-(7H-Imidazo[1,5-c]pyrrolo[3,2-e]pyrimidinyl)piperidinyl]oxopropanenitrile Benzyl 3-(7H-imidazo[1,5-c]pyrrolo[3,2-e]pyrimidinyl)piperidinecarboxylate (13.3 mg, 0.0354 mmol) and 10% palladium hydroxide-carbon (small amount) in ethanol (1.5 mL) was stirred at room temperature for 2.5 hours under a hydrogen atmosphere.

The reaction mixture was filtered, and the filtrate was concentrated under reduced 40 pressure. The resulting residue was dissolved in N,N-dimethylformamide (1 mL) and stirred with 2-cyanoacetic acid (5.0 mg, 0.054 mmol), O-(7-azabenzotriazolyl)- N,N,N’,N’-tetramethyluronium hexafluorophosphate (27.5 mg, 0.0722 mmol) and N,N- diisopropylethylamine (19.0 µL, 0.11 mmol) at room temperature for one day. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic 45 layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (NH-PLC05 plate manufactured by Fuji Silysia Chemical Ltd.: chloroform / methanol =15/1 (v/v)) to give the title compound as a pale yellow oil (1.02 mg, yield 11%).

SYNTHETIC EXAMPLE 5 1-o-Tolyl-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine (7H-Pyrrolo[2,3-d]pyrimidinyl)(o-tolyl)methanone (50.0 mg, 0.211 mmol) obtained in Reference Synthetic Example 10 in methanol (1 ml) was stirred with hydrazine monohydrate (295 µL, 9.48 mmol) at 75°C for 7 hours. After addition of water and 1 M aqueous sodium hydroxide, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue (pale yellow amorphous, 60.3 mg) was dissolved in chloroform (4 mL) and stirred with manganese dioxide (91.6 mg, 1.05 mmol) at 75°C for 6 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 4/1 → 1/1 (v/v)) to give the title compound as a white solid (21.5 mg, yield 41%).

SYNTHETIC EXAMPLE 6 1-Cyclohexyl-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine The reactions in Synthetic Example 5 were carried out in substantially the same manners except that cyclohexyl(7H-pyrrolo[2,3-d]pyrimidinyl)methanone obtained in Reference Synthetic Example 12 was used instead of (7H-pyrrolo[2,3-d]pyrimidin yl)(o-tolyl)methanone to give the title compound as a pale yellow solid (76.6 mg, yield 73%).

SYNTHETIC EXAMPLE 7 1-(2-Methylcyclohexyl)-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine The reactions in Synthetic Example 5 were carried out in substantially the same manners except that (2-methylcyclohexyl)(7H-pyrrolo[2,3-d]pyrimidinyl)methanone obtained in Reference Synthetic Example 14 was used instead of (7H-pyrrolo[2,3- d]pyrimidinyl)(o-tolyl)methanone to give the title compound as a pale yellow amorphous (16.9 mg, yield 32%).

SYNTHETIC EXAMPLE 8 1-Cyclohexyl-2H-imidazo[1,5-c]pyrrolo[3,2-e]pyrimidine-3(7H)-thione Cyclohexyl(7H-pyrrolo[2,3-d]pyrimidinyl)methanone (50 mg, 0.22 mmol) obtained in Reference Synthetic Example 12 in methanol (1 mL) was stirred with hydroxylamine (50 wt% aq., 735 µL, 12.0 mmol) at 75°C for 6 hours. After addition of water and 1 M aqueous sodium hydroxide, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue (colorless oil, 53.0 mg) was dissolved in methanol (3 mL) and stirred with zinc (128 mg, 1.96 mmol) and acetic acid (37.5 µL, 0.654 mmol) at 75°C for 7 hours, and the reaction mixture was filtered.

Chloroform and saturated aqueous sodium hydrogen carbonate were added to the 40 filtrate, and the precipitate was separated by filtration. The filtrate was extracted with chloroform, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue (pale yellow oil, 23.7 mg) was dissolved in methanol (1 mL) and stirred with carbon disulfide (62.0 µL, 1.03 mmol) and triethylamine (43.0 µL, 0.309 mmol) at 75°C for 2 hours. The reaction mixture was 45 concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (Hi Flash column amino type manufactured by Yamazen Corporation: chloroform / methanol = 10/1 (v/v)) to give the title compound as a yellow solid (22.6 mg, yield 38%).

SYNTHETIC EXAMPLE 9 1-Cyclohexyl-2H-imidazo[1,5-c]pyrrolo[3,2-e]pyrimidin-3(7H)-one Cyclohexyl(7H-pyrrolo[2,3-d]pyrimidinyl)methanone (100 mg, 0.436 mmol) obtained in Reference Synthetic Example 12 in methanol (2 mL) was stirred with hydroxylamine (50 wt% aq., 1.34 mL, 21.8 mmol) at 75°C for 5 hours. After addition of water and 1 M aqueous sodium hydroxide, the reaction mixture was extracted with chloroform. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure.

The resulting residue (colorless oil, 110 mg) was dissolved in methanol (3 mL) and stirred with zinc (258 mg, 3.93 mmol) and acetic acid (75.0 µL, 1.31 mmol) at 70°C for 7.5 hours, and the reaction mixture was filtered. Chloroform and saturated aqueous sodium hydrogen carbonate were added to the filtrate, and the precipitate was separated by filtration. The filtrate was extracted with dichloromethane, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue (pale yellow amorphous, 57.5 mg) was dissolved in chloroform (1 mL) and stirred with triphosgene (29.6 mg, 0.0999 mmol) at room temperature for 3 hours. After addition of methanol, the reaction mixture was purified by silica gel column chromatography (Hi Flash column amino type manufactured by Yamazen Corporation: chloroform / methanol = 10/1 (v/v)) to give the title compound as a yellow solid (6.0 mg, yield 5.4%).

SYNTHETIC EXAMPLE 10 [trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]methanol 1-{trans[(tert-Butyldiphenylsilyloxy)methyl]cyclohexyl}-7H-pyrrolo[3,2- e][1,2,3]triazolo[1,5-c]pyrimidine (48.0 mg, 0.0942 mmol) obtained in Reference Synthetic Example 24 in tetrahydrofuran (3 mL) was cooled with ice and stirred with tetrabutylammonium fluoride (1.0 M solution in tetrahydrofuran, 104 µL, 0.104 mmol) for 4 hours while the temperature was gradually raised to room temperature. After addition of water, the reaction solution was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform / methanol = 10/1 (v/v)) to give the title compound as a pale yellow solid (25.3 mg, yield 99%).

SYNTHETIC EXAMPLE 11 tert-Butyl 4-methyl(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)piperidine carboxylate The reactions in Synthetic Example 5 were carried out in substantially the same manners except that tert-butyl 4-methyl(7H-pyrrolo[2,3-d]pyrimidine carbonyl)piperidinecarboxylate obtained in Reference Synthetic Example 27 was 40 used instead of (7H- pyrrolo[2,3-d]pyrimidinyl)(o-tolyl)methanone to give the title compound as a pale yellow solid (1.0 mg, yield 1.3%).

SYNTHETIC EXAMPLE 12 3-[4-Methyl(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)piperidinyl] oxopropanenitrile 45 tert-Butyl 4-methyl(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)piperidinecarboxylate (5.6 mg, 0.016 mmol) in 4 M hydrogen chloride - 1,4-dioxane solution (1.0 mL) was stirred under cooling with ice for 1 hour and concentrated under reduced pressure. The residue was dissolved in N,N-dimethylformamide (1 mL) and mixed with 2-cyanoacetic acid (2.7 mg, 0.0314 mmol) and O-(7-azabenzotriazolyl)- N,N,N’,N’-tetramethyluronium hexafluorophosphate (11.9 mg, 0.0314 mmol) and then with N,N-diisopylethylamine (0.0082 mL, 0.0471 mmol) and stirred at room temperature for 2 hours. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (NH-PLC05 plate manufactured by Fuji Silysia Chemical Ltd.: chloroform / methanol =15/1 (v/v)) and further purified by silica gel thin layer chromatography (ethyl acetate) to give the title compound as a pale yellow solid (0.62 mg, yield 12%).

SYNTHETIC EXAMPLE 13 tert-Butyl 3-(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)piperidinecarboxylate The reactions in Synthetic Example 5 were carried out in substantially the same manners except that tert-butyl 3-(7H-pyrrolo[2,3-d]pyrimidinecarbonyl)piperidine carboxylate obtained in Reference Synthetic Example 29 was used instead of (7H- pyrrolo[2,3-d]pyrimidinyl)(o-tolyl)methanone to give the title compound as a pale yellow oil (48.2 mg, yield 47%).

SYNTHETIC EXAMPLE 14 Benzyl 3-(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)piperidinecarboxylate The reactions in Synthetic Example 5 were carried out in substantially the same manners except that benzyl 3-(7H-pyrrolo[2,3-d]pyrimidinecarbonyl)piperidine carboxylate obtained in Reference Synthetic Example 32 was used instead of (7H- pyrrolo[2,3-d]pyrimidinyl)(o-tolyl)methanone to give the title compound as a pale yellow solid (185 mg, yield 85%).

SYNTHETIC EXAMPLE 15 1-(Piperidinyl)-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine Benzyl 3-(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)piperidine carboxylate (25.0 mg, 0.0664 mmol) in ethanol was stirred with 5% palladium-carbon (10 mg) under a hydrogen atmosphere at 50°C for 2.5 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give the title compound as a light brown solid (16.1 mg, yield quantitative).

SYNTHETIC EXAMPLE 16 1-(1-Benzylpiperidinyl)-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine The reactions in Synthetic Example 5 were carried out in substantially the same manners except that (1-benzylpiperidinyl)(7H-pyrrolo[2,3-d]pyrimidinyl)methanone obtained in Reference Synthetic Example 35 was used instead of (7H-pyrrolo[2,3- d]pyrimidinyl)(o-tolyl)methanone to give the title compound as a pale yellow solid (2.6 mg, yield 2.5%). 40 SYNTHETIC EXAMPLE 17 1-[3-(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)piperidinyl]-3,3,3- trifluoropropanone 1-(Piperidinyl)-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine (20.0 mg., 0.0825 mmol) obtained in Synthetic Example 15 in N,N-dimethylformamide (1.5 mL) 45 was mixed with 3,3,3-trifluoropropanoic acid (8.6 µL, 0.099 mmol) and O-(7- azabenzotriazolyl)-N,N,N’,N’-tetramethyluronium hexafluorophosphate (62.7 mg, 0.165 mmol) and then with N,N-diisopropylethylamine (0.0431 ml, 0.248 mmol) and stirred at room temperature for one day. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1/1 → 1/2 (v/v) → ethyl acetate) to give the title compound as a colorless solid (7.3 mg, yield 25%).

SYNTHETIC EXAMPLE 18 1-[1-(Pyridinylmethyl)piperidinyl]-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine 1-(Piperidinyl)-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine (21.9 mg, 0.0903 mmol) obtained in Synthetic Example 15 in methanol (1.5 mL) was stirred with 3- pyridinecarboxyaldehyde (12.7 µL, 0.135 mmol) at 50°C for 1.5 hours, then with a small amount of acetic acid at room temperature for 2 hours and with sodium triacetoxyborohydride (28.6 mg, 0.135 mmol) at room temperature for one day. After addition of water, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Hi Flash column amino type manufactured by Yamazen Corporation: chloroform / methanol = /1 (v/v)) and then by silica gel thin layer chromatography (NH-PLC05 plate manufactured by Fuji Silysia Chemical Ltd.: ethyl acetate) to give the title compound as a colorless solid (5.8 mg, yield 19%).

SYNTHETIC EXAMPLE 19 -{[3-(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)-piperidinyl]methyl}thiazole The reactions in Synthetic Example 18 were carried out in substantially the same manners except that thiazolecarbaldehyde was used instead of 3- pyridinecarboxyaldehyde to give the title compound as a colorless solid (3.4 mg, yield 12%).

SYNTHETIC EXAMPLE 20 3-(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)-N-(1,3,4-thiadiazol yl)piperidinecarboxamide 1-(Piperidinyl)-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine (22.1 mg, 0.0912 mmol) obtained in Synthetic Example 15 in tetrahydrofuran (1.5 mL) was stirred with phenyl 1,3,4-thiadiazolylcarbamate (24.1 mg, 0.109 mmol) obtained in Reference Synthetic Example 36 and triethylamine (0.0191 mg, 0.137 mmol) at 60°C for 1.5 hours and then stirred at room temperature for one day. The precipitate in the reaction mixture was washed with ethyl acetate, methanol and tetrahydrofuran, and the solid was dried under reduced pressure to give the title compound as a light brown solid (2.4 mg, yield 7%).

SYNTHETIC EXAMPLE 21 N-(3-Methylisothiazolyl)(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)piperidinecarboxamide 40 1-(Piperidinyl)-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine (23.2 mg., 0.0957 mmol) obtained in Synthetic Example 15 in tetrahydrofuran (1.5 mL) was stirred with phenyl (3-methylisothiazolyl)carbamate (26.9 mg, 0.115 mmol) obtained in Reference Synthetic Example 37 and triethylamine (0.0201 mL, 0.144 mmol) at 60°C for 1.5 hours. After addition of water, the reaction mixture was extracted with ethyl 45 acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Hi Flash column amino type manufactured by Yamazen Corporation: chloroform / methanol = 7/1 (v/v)), and the resulting solid was washed with ethyl acetate, methanol and tetrahydrofuran to give the title compound as a light brown solid (3.0 mg, yield 8.3%).

SYNTHETIC EXAMPLE 22 4-{[3-(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)piperidin yl]methyl}benzonitrile 1-(Piperidinyl)-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine (29.4 mg., 0.121 mmol) obtained in Synthetic Example 15 in acetonitrile (1.5 mL) was stirred with 4- (bromomethyl)benzonitrile (31.0 mg, 0.168 mmol) and N,N-diisopropylethylamine (0.0317 mL, 0.182 mmol) at 60°C for 2 hours. The reaction mixture was purified by silica gel column chromatography (Hi Flash column amino type manufactured by Yamazen Corporation: hexane / ethyl acetate = 1/1 (v/v) → ethyl acetate) to give the title compound as a colorless solid (24.9 mg, yield 58%).

SYNTHETIC EXAMPLE 23 1-{1-[4-(Trifluoromethyl)benzyl]piperidinyl}-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5- c]pyrimidine The reactions in Synthetic Example 22 were carried out in substantially the same manners except that 1-(bromomethyl)(trifluoromethyl)benzene was used instead of 4- (bromomethyl)benzonitrile to give the title compound as a light brown solid (30.9 mg, yield 68%).

SYNTHETIC EXAMPLE 24 tert-Butyl 4-(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)piperidinecarboxylate The reactions in Synthetic Example 5 were carried out in substantially the same manners except that tert-butyl 4-(7H-pyrrolo[2,3-d]pyrimidincarbonyl)piperidine carboxylate obtained in Reference Synthetic Example 39 was used instead of (7H- pyrrolo[2,3-d]pyrimidinyl)(o-tolyl)methanone to give the title compound as a pale yellow solid (157 mg, yield 69%).

SYNTHETIC EXAMPLE 25 1-[1-(2,2,2-Trifluoroethyl)piperidinyl]-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine The reactions in Synthetic Example 5 were carried out in substantially the same manners except that (7H-pyrrolo[2,3-d]pyrimidinyl)[1-(2,2,2-trifluoroethyl)piperidin yl]methanone obtained in Reference Synthetic Example 42 was used instead of (7H- pyrrolo[2,3-d]pyrimidinyl)(o-tolyl)methanone to give the title compound as a pale yellow solid (6.6 mg, yield 12%).

SYNTHETIC EXAMPLE 26 Benzyl 4-(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)piperidinecarboxylate The reactions in Synthetic Example 5 were carried out in substantially the same manners except that benzyl 4-(7H-pyrrolo[2,3-d]pyrimidinecarbonyl)piperidine carboxylate obtained in Reference Synthetic Example 44 was used instead of (7H- 40 pyrrolo[2,3-d]pyrimidinyl)(o-tolyl)methanone to give the title compound as a colorless solid (49.6 mg, yield 34%).

SYNTHETIC EXAMPLE 27 1-(Piperidinyl)-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine % Palladium-carbon (10.0 mg) was added to benzyl 4-(7H-pyrrolo[3,2- 45 e][1,2,3]triazolo[1,5-c]pyrimidinyl)piperidinecarboxylate (30.0 mg, 0.0800 mmol) in methanol (2 mL) under an argon atmosphere, and after the reaction system was flushed with hydrogen, the reaction mixture was stirred at room temperature for 6 hours and then filtered. The filtrate was concentrated under reduced pressure. The resulting yellow solid was washed with methanol and collected by filtration to give the title compound as a pale yellow solid (5.0 mg, yield 26%).

SYNTHETIC EXAMPLE 28 1-[1-(Pyridinylmethyl)piperidinyl]-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine 1-(Piperidinyl)-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine (11.0 mg, 0.0450 mmol) in a mixture of methanol (1 mL) and tetrahydrofuran (1 mL) was stirred with 3- pyridinecarboxyaldehyde (5.0 µL, 0.054 mmol), acetic acid (33 µL) and sodium cyanoborohydride (4.3 mg, 0.068 mmol) at room temperature for one day. The reaction mixture was stirred with sodium triacetoxyborohydride (10.0 mg, 0.047 mmol) for another 2 hours. The resulting reaction mixture was purified by silica gel thin layer chromatography (methanol / chloroform = 1/9 (v/v)) twice to give the title compound as a colorless solid (1.4 mg, yield 9.3%).

SYNTHETIC EXAMPLE 29 1-[4-(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)piperidinyl]-3,3,3- trifluoropropanone 1-(Piperidinyl)-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine acetate (30.0 mg, 0.0992 mmol) obtained in Reference Synthetic Example 104 in N,N-dimethylformamide (1 mL) was stirred with 3,3,3-trifluoropropionic acid (14.0 µL, 0.161 mmol), 1-(3- dimethylaminopropyl)ethylcarbodiimide hydrochloride (48.0 mg, 0.248 mmol), 1- hydroxybenzotriazole (34.0 mg, 0.248 mmol) and triethylamine (43.0 µL, 0.310 mmol) at room temperature for 3 hours and then with water (1 mL) for another 1 day. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 2/1 (v/v)) to give the title compound as a colorless solid (11.7 mg, yield 34%).

SYNTHETIC EXAMPLE 30 4-(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)-N-(1,3,4-thiadiazol yl)piperidinecarboxamide 1-(Piperidinyl)-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine acetate (25.0 mg, 0.0827 mmol) obtained in Reference Synthetic Example 104 in tetrahydrofuran (1 mL) was stirred with phenyl 1,3,4-thiadiazolylcarbamate (27.0 mg, 0.124 mmol) obtained in Reference Synthetic Example 36 and triethylamine (22.0 µL, 0.155 mmol) at room temperature for 2 hours. Water and ethyl acetate were added to the reaction mixture, and the insolubles were collected by filtration. The resulting solid was washed with methanol, chloroform, acetonitrile and ethanol to give the title compound as a colorless solid (19.3 mg, yield 63%).

SYNTHETIC EXAMPLE 31 40 N-(3-Methylisothiazolyl)(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)piperidinecarboxamide The reactions Synthetic Example 30 were carried out in substantially the same manners except that phenyl (3-methylisothiazolyl)carbamate obtained in Reference Synthetic Example 37 was used instead of phenyl 1,3,4-thiadiazolylcarbamate to 45 give the title compound as a pale yellow solid (17.6 mg, yield 56%).

SYNTHETIC EXAMPLE 32 1-(1-Benzylpiperidinyl)-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine 1-(Piperidinyl)-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine acetate (20.0 mg, 0.0662 mmol) obtained in Reference Synthetic Example 104 in acetonitrile (1 mL) was stirred with benzyl bromide (15.0 µL, 0.124 mmol) and N,N-diisopropylethylamine (28.0 µL, 0.166 mmol) at 60°C for 2 hours. The reaction mixture was purified by silica gel column chromatography (methanol / chloroform = 1/30 → 1/25 (v/v)), and the resulting solid was washed with isopropyl ether to give the title compound as a colorless solid (2.92 mg, yield 13%).

SYNTHETIC EXAMPLES 33 TO 43 The reactions in Synthetic Example 32 were carried out in substantially the same manners except that 4-(trifluoromethyl)benzyl bromide, 4-cyanobenzyl bromide, 3- cyanobenzyl bromide, 4-(chloromethyl)-3,5-dimethylisoxazole, 4- (trifluoromethoxy)benzyl bromide, 4-(trifluoromethylthio)benzyl bromide, 3- (trifluoromethyl)benzyl bromide, 4-(bromomethyl)fluorobenzonitrile, 1-bromo (bromomethyl)benzene, 1-(2-bromoethyl)(trifluoromethyl)benzene or 4-fluorobenzyl bromide was used instead of benzyl bromide to give the compounds of Synthetic Examples 33 to 43. The names, morphologies and yields of the synthesized compounds are shown in Table 7.

TABLE 7 SYNTHETIC EXAMPLE 44 -{[4-(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)piperidinyl]methyl}thiazole 1-(Piperidinyl)-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine acetate (20.0 mg, 0.0662 mmol) obtained in Reference Synthetic Example 104 in methanol (1 mL) was stirred with thiazolecarbaldehyde (11.0 µL, 0.124 mmol), acetic acid (100 µL) and 2- picoline borane (13.0 mg, 0.124 mmol) at room temperature for one day. The reaction mixture was purified by silica gel column chromatography (methanol / chloroform = 1/30 → 1/25 → 1/20 (v/v)). The resulting solid was washed with isopropyl ether to give the title compound as a colorless solid (9.05 mg, yield 40%).

SYNTHETIC EXAMPLES 45 TO 55 The reactions in Synthetic Example 44 were carried out in substantially the same manners except that 3-phenylpropionaldehyde, 3-fluoromethoxybenzaldehyde, 3,5- bis(trifluoromethyl)benzaldehyde, 2-formylthiazole, 5-chlorothiophenecarboxaldehyde, cyclohexanecarboxaldehyde, cyclopentanone, 6-(trifluoromethyl) pyridinecarboxaldehyde, 3,5-difluoroformylbenzonitrile, 4-chlorobenzaldehyde or 3- fluorobenzaldehyde was used instead of thiazolecarbaldehyde to give the compounds of Synthetic Examples 45 to 55. The names, morphologies and yields of the compounds synthesized are shown in Table 8.

TABLE 8 SYNTHETIC EXAMPLE 56 1-{1-[4-(Trifluoromethyl)cyclohexyl]piperidinyl}-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5- c]pyrimidine The reactions in Synthetic Example 44 were carried out in substantially the same manners except that 4-(trifluoromethyl)cyclohexanone was used instead of thiazole carbaldehyde to give an isomer mixture as a pale yellow solid. The isomer mixture was purified by silica gel thin layer chromatography (methanol / chloroform = 1/9 (v/v)) to give the two isomers of the title compound in a less polar fraction (Synthetic Example 56a; pale yellow solid, 5.6 mg, yield 22%) and in a more polar fraction (Synthetic Example 56b; pale yellow solid, 4.9 mg, yield 19%).

SYNTHETIC EXAMPLE 57 4-(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)-N-[3- (trifluoromethyl)phenyl]piperidinecarboxamide 1-(Piperidinyl)-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine acetate (20.0 mg, 0.0662 mmol) obtained in Reference Synthetic Example 104 in tetrahydrofuran (1 mL) was stirred with 3-(trifluoromethyl)phenyl isocyanate (14.0 µL, 0.0990 mmol) and triethylamine (14.0 µL, 0.0990 mmol) at room temperature for 3 days. The reaction mixture was purified by silica gel thin layer chromatography (methanol / chloroform = 1/9 (v/v)) to give the title compound as a light gray solid (7.5 mg, yield 27%).

SYNTHETIC EXAMPLE 58 [4-(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)piperidinyl][4- (trifluoromethyl)phenyl]methanone 1-(Piperidinyl)-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine acetate (20.0 mg, 0.0662 mmol) obtained in Reference Synthetic Example 104 in N,N-dimethylformamide (1 mL) was stirred with 4-(trifluoromethyl)benzoyl chloride (14.8 µL, 0.100 mmol) and triethylamine (13.9 µL, 0.100 mmol) under cooling with ice for 80 minutes. After addition of water, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (methanol / chloroform = 1/19 (v/v)) to give the title compound as a colorless oil (16.3 mg, yield 59%).

SYNTHETIC EXAMPLE 59 tert-Butyl [trans(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexyl]carbamate The reactions in Synthetic Example 5 were carried out in substantially the same manners except that tert-butyl [trans(7H-pyrrolo[2,3-d]pyrimidine carbonyl)cyclohexyl]carbamate obtained in Reference Synthetic Example 46 was used instead of (7H-pyrrolo[2,3-d]pyrimidinyl)(o-tolyl)methanone to give the title compound as a colorless solid (4.7 mg, yield 15%).

SYNTHETIC EXAMPLE 60 Benzyl [trans(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexyl]carbamate The reactions in Synthetic Example 5 were carried out in substantially the same manners except that benzyl [trans(7H-pyrrolo[2,3-d]pyrimidine carbonyl)cyclohexyl]carbamate obtained in Reference Synthetic Example 48 was used instead of (7H-pyrrolo[2,3-d]pyrimidinyl)(o-tolyl)methanone to give the title compound as a colorless solid (10.0 mg, yield 29%).

SYNTHETIC EXAMPLE 61 trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexanamine % Palladium-carbon (5.00 mg) was added to benzyl [trans(7H-pyrrolo[3,2- 40 e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]carbamate (7.00 mg, 0.0180 mmol) in a mixture of ethanol (1 mL) and chloroform (1 mL) under an argon atmosphere, and after the reaction system was flushed with hydrogen, the reaction mixture was stirred at room temperature for one day and then filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel thin layer chromatography 45 (NH-PLC05 plate manufactured by Fuji Silysia Chemical Ltd.:methanol /chloroform = 1/19 (v/v)) to give the title compound as a colorless solid (0.35 mg, yield 8.0%).

SYNTHETIC EXAMPLE 62 1-[trans(Methoxymethyl)cyclohexyl]-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine The reactions in Synthetic Example 5 were carried out in substantially the same manners except that [trans(methoxymethyl)cyclohexyl](7H-pyrrolo[2,3-d]pyrimidin yl)methanone obtained in Reference Synthetic Example 50 was used instead of (7H- pyrrolo[2,3-d]pyrimidinyl)(o-tolyl)methanone to give the title compound as a colorless solid (52.4 mg, yield 63%).

SYNTHETIC EXAMPLE 63 1-[transMethoxycyclohexyl]-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine The reactions in Synthetic Example 5 were carried out in substantially the same manners except that (transmethoxycyclohexyl)(7H-pyrrolo[2,3-d]pyrimidin yl)methanone obtained in Reference Synthetic Example 53 was used instead of (7H- pyrrolo[2,3-d]pyrimidinyl)(o-tolyl)methanone to give the title compound as a pale yellow solid (7.80 mg, yield 7.6%).

SYNTHETIC EXAMPLES 64 TO 69 The reactions in Synthetic Example 5 were carried out in substantially the same manners except that the compounds obtained in Reference Synthetic Examples 61 to 66 were used instead of (7H-pyrrolo[2,3-d]pyrimidinyl)(o-tolyl)methanone to give the title compounds of Synthetic Examples 64 to 69. The names, morphologies and yields of the compounds synthesized are shown in Table 9.

TABLE 9 SYNTHETIC EXAMPLE 70 1-[trans(Trifluoromethyl)cyclohexyl]-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine The reactions in Synthetic Example 5 were carried out in substantially the same manners except that (7H-pyrrolo[2,3-d]pyrimidinyl)[cis (trifluoromethyl)cyclohexyl]methanone obtained in Reference Synthetic Example 67 was used instead of (7H-pyrrolo[2,3-d]pyrimidinyl)(o-tolyl)methanone to give the title compound as a colorless solid (12.0 mg, yield 23%). (although the cis-isomer was used as the starting material, only the trans-isomer of the title compound was obtained.) SYNTHETIC EXAMPLE 71 S-{[trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]methyl} ethanethioate Triphenylphosphine (58.0 mg, 0.221 mmol) in tetrahydrofuran (1 mL) was mixed with diisopropyl azodicarboxylate (116 µL, 0.428 mmol) and [trans(7H-pyrrolo[3,2- e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]methanol (30.0 mg, 0.111 mmol) obtained in Synthetic Example 10 and thioacetic acid (16.0 µL, 0.225 mmol) under cooling with ice, and stirred for 30 minutes while the temperature was gradually raised to room temperature. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1/10 → 1/3 (v/v)) to give the title compound as a colorless solid (22.4 mg, yield 62%).

SYNTHETIC EXAMPLE 72 [trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]methyl acetate The reactions in Synthetic Example 71 were carried out in substantially the same manners except that acetic acid was used instead of thioacetic acid to give the title compound as a colorless solid (18.3 mg, yield 53%).

SYNTHETIC EXAMPLE 73 1-[trans(Fluoromethyl)cyclohexyl]-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine [trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]methanol (30.0 mg, 0.111 mmol) obtained in Synthetic Example 10 suspended in dichloromethane (3 mL) was mixed with N,N-diethylaminosulfur trifluoride (16.1 µL, 0.122 mmol) under cooling with ice and stirred for 30 minutes while the temperature was gradually raised to room temperature. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate /hexane =1/5 → 1/3 (v/v)) to give the title compound as a colorless solid (6.7 mg, yield 22%).

SYNTHETIC EXAMPLE 74 1-[trans(Bromomethyl)cyclohexyl]-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine [trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]methanol (50.0 mg, 0.184 mmol) obtained in Synthetic Example 10 in dichloromethane (3 mL) was mixed with triphenylphosphine (58.0 mg, 0.221 mmol) and N-bromosuccinimide (39.0 mg, 0.221 mmol) under cooling with ice and stirred for 19 hours while the temperature was gradually raised to room temperature. The reaction mixture was purified by silica gel column chromatography (ethyl acetate/ hexane = 1/1 (v/v)) to give the title compound as a colorless solid (27.4 mg, yield 44%).

SYNTHETIC EXAMPLE 75 1-[trans(Chloromethyl)cyclohexyl]-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine The reactions in Synthetic Example 74 were carried out in substantially the same 40 manners except that N-chlorosuccinimide was used instead of N-bromosuccinimide to give the title compound as a colorless solid (1.25 mg, yield 2%).

SYNTHETIC EXAMPLE 76 [trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]methanethiol S-{[trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]methyl} 45 ethanethioate (30.0 mg, 0.0911 mmol) obtained in Synthetic Example 71 in methanol (2 mL) was stirred with sodium methoxide (28 wt% solution in methanol, 10 µL) at room temperature for 30 minutes. The solid precipitated in the reaction solution was removed by filtration and washed with methanol. The filtrate and the washings were mixed with water, and the precipitated solid was collected by filtration and dried under reduced pressure to give the title compound as a colorless solid (12.9 mg, yield 49%).

SYNTHETIC EXAMPLE 77 1-{trans[(Methylsulfonyl)methyl]cyclohexyl}-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5- c]pyrimidine 1-[trans(Bromomethyl)cyclohexyl]-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5- c]pyrimidine (27.3 mg, 0.0817 mmol) obtained in Synthetic Example 74 in N,N- dimethylformamide (2 mL) was stirred with sodium methanesulfinate (10.8 mg, 0.106 mmol) at room temperature for 30 minutes and then at 65°C for 1.5 hours. The reaction mixture was allowed to cool to room temperature and stirred with sodium methanesulfinate (21.7 mg, 0.212 mmol) at 65°C for 7.5 hours. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residues was purified by silica gel column chromatography (ethyl acetate / hexane = 1/1 (v/v)) to give the title compound as a colorless solid (5.3 mg, yield 25%).

SYNTHETIC EXAMPLE 78 trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexanecarbaldehyde [trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]methanol (50.0 mg, 0.184 mmol) obtained in Synthetic Example 10 in a mixture of toluene (1 mL) and dimethyl sulfoxide (200 µL) was stirred with 2-iodoxybenzoic acid (62.0 mg, 0.221 mmol) at room temperature for 30 minutes and at 50°C for 3 hours. After addition of saturated aqueous sodium hydrogen carbonate, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure.

The residues was purified by silica gel column chromatography (ethyl acetate / hexane = 1/1 (v/v)) to give the title compound as a colorless solid (38.0 mg, yield 77%).

SYNTHETIC EXAMPLE 79 1-[trans(Difluoromethyl)cyclohexyl]-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine The reactions in Synthetic Example 73 were carried out in substantially the same manners except that trans(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexanecarbaldehyde was used instead of [trans(7H-pyrrolo[3,2- e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]methanol to give the title compound as a colorless solid (21.1 mg, yield 65%).

SYNTHETIC EXAMPLE 80 trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexanecarboxylic acid trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexanecarbaldehyde (25.8 mg, 0.0958 mmol) obtained in Synthetic Example 40 78 in t-butanol (0.31 mL) was mixed with sodium dihydrogen phosphate (34.4 mg, 0.287 mmol), water (0.31 mL) and 2-methylbutene (0.31 mL, 2.87 mmol) and then with sodium chlorite (43.3 mg, 0.479 mmol) and stirred at room temperature for 2 hours.

After addition of saturated aqueous sodium thiosulfate, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium 45 sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform / methanol = 10/1 → 4/1 → 2/1 (v/v)) to give the title compound as a colorless solid (14.7 mg, yield 54%).

SYNTHETIC EXAMPLE 81 trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexanol 1-{4-[(tert-Butyldiphenylsilyl)oxy]cyclohexyl}-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5- c]pyrimidine (400 mg, 0.807 mmol) obtained in Reference Synthetic Example 70 in tetrahydrofuran (8 mL) was mixed with tetrabutylammonium fluoride (1 M solution in tetrahydrofuran, 0.97 mL, 0.986 mmol) under cooling with ice and stirred at room temperature for 2 hours and then at 40°C for 1.5 hours. The reaction solution was stirred with tetrabutylammonium fluoride (1 M solution in tetrahydrofuran, 0.458 mL, 0.484 mmol) at 40°C for 1 hour. After addition of water, the reaction solution was extracted with chloroform, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate → chloroform / methanol = 10/1 (v/v)) to give the title compound as a colorless solid (78.1 mg, yield 37%).

SYNTHETIC EXAMPLE 82 4-(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexanone The reactions in Synthetic Example 78 were carried out in substantially the same manners except that trans(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexanol was used instead of [trans(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5- c]pyrimidinyl)cyclohexyl]methanol to give the title compound as a pale yellow solid (27.1 mg, yield 35%).

SYNTHETIC EXAMPLE 83 cis(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexanol 1-{4-[(tert-Butyldimethylsilyl)oxy]cyclohexyl}-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5- c]pyrimidine (1.18 g, 3.16 mmol) obtained in Reference Synthetic Example 74 in tetrahydrofuran (10 mL) was stirred with tetrabutylammonium fluoride (1 M solution in tetrahydrofuran, 3.8 mL, 3.79 mmol) at room temperature for 15 hours and then with tetrabutylammonium fluoride (1 M solution in tetrahydrofuran, 7.6 mL, 7.58 mmol) at 60°C for 8 hours and then allowed to cool to room temperature. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1/1 (v/v) → ethyl acetate) to give a less polar fraction (colorless solid, 237 mg) and a more polar fraction (colorless solid, 438 mg).

The less polar fraction was stirred with tetrabutylammonium fluoride (1 M solution in tetrahydrofuran, 440 µL) at room temperature for 4 days. After addition of water, the reaction solution was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate was purified by silica gel 40 column chromatography (hexane/ ethyl acetate = 1/1 (v/v) → ethyl acetate) to give the title compound as a colorless solid (66.4 mg, yield 14%).

SYNTHETIC EXAMPLE 84 Benzyl 4-(7H-imidazo[1,5-c]pyrrolo[3,2-e]pyrimidinyl)piperidinecarboxylate The reactions in Synthetic Example 3 were carried out in substantially the same 45 manners except that benzyl 4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-imidazo[1,5- c]pyrrolo[3,2-e]pyrimidinyl)piperidinecarboxylate obtained in Reference Synthetic Example 78 was used instead of benzyl 3-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H- imidazo[1,5-c]pyrrolo[3,2-e]pyrimidinyl)piperidinecarboxylate to give the title compound as a yellow solid (4.6 mg, yield 2%).

SYNTHETIC EXAMPLE 85 Benzyl 4-(3-thioxo-3,7-dihydro-2H-imidazo[1,5-c]pyrrolo[3,2-e]pyrimidinyl)piperidine- 1-carboxylate Benzyl 4-[amino(7H-pyrrolo[2,3-d]pyrimidinyl)methyl]piperidinecarboxylate (50.0 mg, 0.137 mmol) obtained in Reference Synthetic Example 79 in methanol (1 mL) was stirred with carbon disulfide (81.0 µL, 1.35 mmol) and triethylamine (56.0 µL, 0.405 mmol) at 75°C for 1.5 hours. The reaction mixture was allowed to cool to room temperature, and the precipitated solid was collected by filtration and washed with methanol to give the title compound as a yellow solid (28.0 mg, yield 51%).

SYNTHETIC EXAMPLE 86 1-{1-[4-(Trifluoromethyl)benzyl]piperidinyl}-2H-imidazo[1,5-c]pyrrolo[3,2-e]pyrimidine- 3-(7H)-thione The reactions in Synthetic Example 85 were carried out in substantially the same manners except that (7H-pyrrolo[2,3-d]pyrimidinyl){1-[4- (trifluoromethyl)benzyl]piperidinyl}methanamine obtained in Reference Synthetic Example 82 was used instead of benzyl 4-[amino(7H-pyrrolo[2,3-d]pyrimidin yl)methyl]piperidinecarboxylate to give the title compound as a yellow solid (2.6 mg, yield 4%).

SYNTHETIC EXAMPLE 87 Benzyl 3-(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)azetidinecarboxylate The reactions in Synthetic Example 5 were carried out in substantially the same manners except that benzyl 3-(7H-pyrrolo[2,3-d]pyrimidinecarbonyl)azetidine carboxylate obtained in Reference Synthetic Example 84 was used instead of (7H- pyrrolo[2,3-d]pyrimidinyl)(o-tolyl)methanone to give the title compound as a yellow solid (186 mg, yield 60%).

SYNTHETIC EXAMPLE 88 4-{[trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexyl]methyl}thiomorpholine 1,1-dioxide trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexanecarbaldehyde (30.0 mg, 0.111 mmol) obtained in Synthetic Example 78 in a mixture of methanol (2 mL) and acetic acid (200 µL) was stirred with thiomorpholine 1,1-dioxide (22.6 mg, 0.167 mmol) at room temperature for 1 hour, and then with 2- picoline borane (17.9 mg, 0.167 mmol) at room temperature for another 3 hours. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. A mixture of ethyl acetate (1 mL), hexane (1 mL) and chloroform (100 µL) was added to the residue, and 40 the precipitated solid was collected by filtration to give the title compound as a colorless solid (28.3 mg, yield 65%).

SYNTHETIC EXAMPLES 89 TO 120 The reactions in Synthetic Example 88 were carried out in substantially the same manners except that piperidincarbonitrile, 3-aminopropanenitrile, morpholine, 4- 45 aminobenzonitrile, 4-(aminomethyl)benzonitrile hydrochloride, (S)fluoropyrrolidine, (R)fluoropyrrolidine, 3,3-dimethylazetidine hydrochloride, 4,4-difluoropiperidine hydrochloride, [4-(trifluoromethyl)phenyl]methanamine, 4-(trifluoromethyl)aniline, 4- fluoroaniline, (4-fluorophenyl)methanamine, 4-fluoro-N-methylaniline, 4-amino methylbenzonitrile, 2-methyl(trifluoromethoxy)aniline, 4-amino (trifluoromethyl)benzonitrile, (5-methylthiophenyl)methanamine hydrochloride, 2- fluoroethanamine hydrochloride, 4-(methylamino)benzonitrile, 1-(3,4- difluorophenyl)ethanamine, [4-(trifluoromethoxy)phenyl]methanamine, 2-(4- fluorophenyl)ethanamine, [4-fluoro(trifluoromethyl)phenyl]methanamine, [4- (methylsulfonyl)phenyl]methanamine, 4-(trifluoromethoxy)aniline, 2-chloro (triluforomethoxy)aniline, 2-aminofluorobenzonitrile, 4-fluoro(trifluoromethyl)aniline, 4-morpholinoaniline, (S)-pyrrolidinol hydrochloride or (S)-(tetrahydrofuran yl)methanamine was used instead of thiomorpholine 1,1-dioxide to give the compounds of Synthetic Examples 89 to 120. The names, morphologies and yields of the compounds synthesized are shown in Tables 10 to 12.

TABLE 10 TABLE 11 TABLE 12 SYNTHETIC EXAMPLE 121 4-{[4-(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]amino}benzonitrile 4-(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexanone (21.5 mg, 0.0842 mmol) obtained in Synthetic Example 82 in a mixture of methanol (1 mL) and acetic acid (0.1 mL) was stirred with 4-aminobenzonitrile (15.0 mg, 0.126 mmol) and 2- picoline borane (13.5 mg, 0.126 mmol) at room temperature for one day. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel thin layer chromatography (NH-PLC05 plate manufactured by Fuji Silysia Chemical Ltd.: ethyl acetate) to give cis/trans mixture of the title compound as a pale yellow solid (17.1 mg, yield 57%).

SYNTHETIC EXAMPLES 122 TO 133 The reactions in Synthetic Example 121 were carried out in substantially the same manners except that 2-(pyridinyl)ethanamine, 2-phenylethanamine, morpholine, 2-[3-(trifluoromethyl)phenyl]ethanamine, 2-morpholinoethanamine, piperidine carbonitrile, 4-(trifluoromethyl)aniline, 4-aminofluorobenzonitrile, 4-fluoro-N- methylaniline, 4-fluoroaniline, 4-aminomethylbenzonitrile or 2-methyl (trifluoromethoxy)aniline was used instead of 4-aminobenzonitrile to give the compounds of Synthetic Examples 122 to 133. The names, morphologies and yields of the compounds synthesized are shown in Table 13.

TABLE 13 SYNTHETIC EXAMPLE 134 134a: 4-{[cis(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexyl]amino}benzonitrile 134b: 4-{[trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexyl]amino}benzonitrile 4-{[4-(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexyl]amino}benzonitrile (16.5 mg, 0.462 mmol) obtained in Synthetic Example 121 was resolved by silica gel thin layer chromatography (hexane / ethyl acetate =1/2 (v/v)) into 4-{[cis(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexyl]amino}benzonitrile (Synthetic Example 134a; pale yellow solid, 7.3 mg, yield 44%) in a less polar fraction and into 4-{[trans(7H-Pyrrolo[3,2- e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]amino}benzonitrile (Synthetic Example 134b; pale yellow solid, 3.0 mg, yield 18%) in a more polar fraction.

SYNTHETIC EXAMPLE 135 135a: cis-N-Phenethyl(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexanamine 135b: trans-N-Phenethyl(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexanamine The reactions in Synthetic Example 134 were carried out in substantially the same manners except that N-phenethyl(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5- c]pyrimidinyl)cyclohexanamine obtained in Synthetic Example 123 was used instead of 4-{[4-(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexyl]amino}benzonitrile to give cis-N-phenethyl(7H-pyrrolo[3,2- e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexanamine (Synthetic Example 135a; colorless solid, 3.22 mg, yield 16%) in a less polar fraction and trans-N-phenethyl (7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexanamine (Synthetic Example 135b; colorless solid, 2.52 mg, yield 11%) in a more polar fraction.

SYNTHETIC EXAMPLE 136 136a: cis-N-(3-Phenylpropyl)(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexanamine 136b: trans-N-(3-Phenylpropyl)(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexanamine 4-(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexanone (30.0 mg, 0.118 mmol) obtained in Synthetic Example 82 in a mixture of methanol (1.5 ml) and acetic acid (0.15 mL) was mixed with 3-phenylpropanamine (25.0 µL, 0.176 mmol) at room temperature and stirred at 40°C for 30 minutes. The reaction mixture was allowed to cool to room temperature and stirred with 2-picoline borane (19.0 mg, 0.176 mmol) at room temperature for one day. After addition of 1 M hydrochloric acid and ethyl acetate, the aqueous layer was separated, and after addition of 1 M aqueous sodium hydroxide, extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel chromatography (Hi Flash amino silica gel column manufactured by Yamazen Corporation: ethyl acetate / hexane = 1/1 (v/v) → ethyl acetate) to give cis-N-(3-phenylpropyl)(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5- c]pyrimidinyl)cyclohexanamine (Synthetic Example 136a; colorless oil, 6.00 mg, yield 13%) in a less polar fraction and trans-N-(3-phenylpropyl)(7H-pyrrolo[3,2- e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexanamine (Synthetic Example 136b; colorless solid, 2.52 mg, yield 5.7%) in a more polar fraction.

SYNTHETIC EXAMPLES 137 TO 139 The reactions in Synthetic Example 136 were carried out in substantially the same manners except that 4-(aminomethyl)benzonitrile, [4- 40 (trifluoromethyl)phenyl]methanamine or morpholinamine was used instead of 3- phenylpropanamine to give the compounds of Synthetic Examples 137a to 139a in less polar fractions and the compounds of Synthetic Examples 137b to 139b in more polar fractions. The names, morphologies and yields of the compounds synthesized are shown in Table 14.

TABLE 14 SYNTHETIC EXAMPLE 140 [4-(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)phenyl]methanol 1-(4-{[(tert-Butyldimethylsilyl)oxy]methyl}phenyl)-7H-pyrrolo[3,2- e][1,2,3]triazolo[1,5-c]pyrimidine (3.58 g, 9.43 mmol) obtained in Reference Synthetic Example 88 in a mixture of dichloromethane (20 mL) and methanol (50 mL) was stirred with pyridinium p-toluenesulfonate (1.18 g, 4.72 mmol) at 60°C for 8 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1/1 (v/v) → ethyl acetate → ethyl acetate / methanol = 1/1 (v/v)) to give the title compound as an ivory solid (831 mg, yield 33%).

SYNTHETIC EXAMPLE 141 [trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]methanol The reactions in Synthetic Example 140 were carried out in substantially the same manners except that 1-(trans{[(tert-butyldimethylsilyl)oxy]methyl}cyclohexyl)- 7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine obtained in Reference Synthetic Example 92 was used instead of 1-(4-{[(tert-butyldimethylsilyl)oxy]methyl}phenyl)-7H- pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine to give the title compound as a pale yellow solid (2.05 g, yield 78%). (alternative to Synthetic Example 10).

SYNTHETIC EXAMPLES 142 TO 144 The reactions in Synthetic Example 32 were carried out in substantially the same manners except that 1-(bromomethyl)fluorobenzene, 2-(bromomethyl) (trifluoromethyl)furan or 5-(bromomethyl)thiophenecarbonitrile (Reference Synthetic Example 93) was used instead of benzyl bromide to give the compounds of Synthetic Examples 142 to 144. The names, morphologies and yields of the compounds synthesized are shown in Table 15.

TABLE 15 SYNTHETIC EXAMPLES 145 TO 171 The reactions in Synthetic Example 44 were carried out in substantially the same manners except that 6-fluoronicotinaldehyde, furancarbaldehyde, 5-iodofuran carbaldehyde, thiophenecarbaldehyde, 5-bromofurancarbaldehyde, 2- chlorothiazolecarbaldehyde, 1H-pyrazolecarbaldehyde, 1,2,3-thiadiazole carbaldehyde, 2-bromothiazolecarbaldehyde, 4-fluoro (trifluoromethyl)benzaldehyde, 4-chloro(trifluoromethyl)benzaldehyde, 4- (methylsulfonyl)benzaldehyde, 2-fluoro(trifluoromethyl)benzaldehyde, 4-chloro fluorobenzaldehyde, 4-chlorofluorobenzaldehyde, 2-chloroisonicotinaldehyde, 3- fluoroisonicotinaldehyde, 5-fluoropyridinecarbaldehyde, 3-chloroisonicotinaldehyde, 2,4-difluorobenzaldehyde, 2-chlorofluorobenzaldehyde, 3,4-difluorobenzaldehyde, 3- fluoro(trifluoromethyl)benzaldehyde, 4-(2-hydroxyethoxy)benzaldehyde, 4-(1,1,2,2- tetrafluoroethoxy)benzaldehyde, 6-methoxynicotinaldehyde or tert-butyl (2- oxoethyl)carbamate was used instead of thiazolecarbaldehyde to give the compounds of Synthetic Examples 145 to 171. The names, morphologies and yields of the compounds synthesized are shown in Tables 16 and 17.

TABLE 16 TABLE 17 SYNTHETIC EXAMPLES 172 TO 193 The reactions in Synthetic Example 88 were carried out in substantially the same manners except that 3-amino-1,1,1-trifluorophenylpropanol (Reference Synthetic Example 101), 4-[(trifluoromethyl)sulfonyl]aniline, 2-phenylethanamine, 2- (trifluoromethyl)-1H-benzo[d]imidazolamine, 4-chloroaniline, (4- chlorophenyl)methanamine, 2-(4-chlorophenyl)ethanamine, 5-fluoroindoline, 3,3’- azanediyldipropanenitrile, (S)-N,N-dimethylpyrrolidinamine, (5-methylfuran yl)methanamine, (5-methylpyrazinyl)methanamine, (S)aminopropanol, (R) aminopropanol, 2-aminophenylethanol, (S)-pyrrolidinecarbonitrile hydrochloride, 2,2,2-trifluoroethanamine, 5-(methylsulfonyl)indoline, N,N-dimethylindoline sulfonamide, 1-(2-aminoethyl)imidazolidinon, 2-(1H-imidazolyl)ethanamine dihydrochloride or phenylmethanamine was used instead of thiomorpholine 1,1-dioxide to give the compounds of Synthetic Examples 172 to 193. The names, morphologies and yields of the compounds synthesized are shown in Tables 18 and 19.

TABLE 18 TABLE 19 SYNTHETIC EXAMPLES 194 TO 197 The reactions in Synthetic Example 136 were carried out in substantially the same manners except that phenylmethanamine, (4-fluorophenyl)methanamine, 3- amino-1,1,1-trifluorophenylpropanol (Reference Synthetic Example 101) or (4- chlorophenyl)methanamine was used instead of 3-phenylpropanamine to give the compounds of Synthetic Examples 194a to 197a in less polar fractions and the compounds of Synthetic Examples 194b to 197b in more polar fractions. The names, morphologies and yields of the compounds synthesized are shown in Table 20.

TABLE 20 SYNTHETIC EXAMPLES 198 TO 204 The reactions in Synthetic Example 136 were carried out in substantially the same manners except that 2-(4-chlorophenyl)ethanamine, 3-amino(4-chlorophenyl)- 1,1,1-trifluoropropanol (Reference Synthetic Example 100), 3-amino-1,1,1-trifluoro- 2-(4-fluorophenyl)propanol (Reference Synthetic Example 102), 2-(4- fluorophenyl)ethanamine, 2-aminophenylethanol, (S)aminophenylethanol or (R)aminophenylethanol was used instead of 3-phenylpropanamine to give the compounds of Synthetic Examples 198b to 204b in more polar fractions. The names, morphologies and yields of the compounds synthesized are shown in Table 21.

TABLE 21 SYNTHETIC EXAMPLE 205 N-[4-(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]chloroaniline The reactions in Synthetic Example 121 were carried out in substantially the same manners except that 4-chloroaniline was used instead of 4-aminobenzonitrile to give the title compound as a colorless solid (10.2 mg, yield 28%).

SYNTHETIC EXAMPLE 206 trans-N-(4-Fluorophenyl)(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexanecarboxamide trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexanecarboxylic acid (19.5 mg, 0.0683 mmol) obtained in Synthetic Example 80 in N,N- dimethylformamide (1.5 mL) was mixed with 4-fluoroaniline (0.0977 mL, 0.102 mmol) and O-(7-azabenzotriazolyl)-N,N,N’,N’-tetramethyluronium hexafluorophosphate (38.8 mg, 0.102 mmol) and then with N,N-diisopropylethylamine (0.0238 mL, 0.137 mmol) and stirred at room temperature for 3 hours. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (NH-PLC05 plate manufactured by Fuji Silysia Chemical Ltd.: ethyl acetate). The resulting solid was washed with methanol to give the title compound as a colorless solid (6.45 mg, yield 25%).

SYNTHETIC EXAMPLES 207 TO 209 The reactions in Synthetic Example 206 were carried out in substantially the same manners except that (4-fluorophenyl)methanamine, 2-(4-fluorophenyl)ethanamine or (S)fluoropyrrolidine was used instead of 4-fluoroaniline to give the compounds of Synthetic Examples 207 to 209. The names, morphologies and yields of the compounds synthesized are shown in Table 22.

TABLE 22 SYNTHETIC EXAMPLE 210 4-{[4-(7H-Imidazo[1,5-c]pyrrolo[3,2-e]pyrimidinyl)piperidinyl]methyl}benzonitrile The reactions in Synthetic Example 3 were carried out in substantially the same manners except that 4-{[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-imidazo[1,5- c]pyrrolo[3,2-e]pyrimidinyl)piperidinyl]methyl}benzonitrile obtained in Reference Synthetic Example 97 was used instead of benzyl 3-(7-{[2- (trimethylsilyl)ethoxy]methyl}-7H-imidazo[1,5-c]pyrrolo[3,2-e]pyrimidinyl)piperidine carboxylate to give the title compound as a brown solid (1.3 mg, yield 4%).

SYNTHETIC EXAMPLE 211 Benzyl 3-(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)pyrrolidinecarboxylate The reactions in Synthetic Example 5 were carried out in substantially the same manners except that benzyl 3-(7H-pyrrolo[2,3-d]pyrimidinecarbonyl)pyrrolidine carboxylate obtained in Reference Synthetic Example 99 was used instead of (7H- pyrrolo[2,3-d]pyrimidinyl)(o-tolyl)methanone to give the title compound as a colorless solid (27.4 mg, yield 2%).

SYNTHETIC EXAMPLE 212 2-[4-(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)piperidinyl][4- (trifluoromethyl)phenyl]ethanol 1-(Piperidinyl)-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine acetate (33.1 mg, 0.110 mmol) obtained in Reference Synthetic Example 104 in ethanol (3 mL) was stirred with water (0.5 mL), triethylamine (0.1 mL), ytterbium (III) trifluoromethanesulfonate (12.7 mg, 0.0237 mmol) and 2-[4- (trifluoromethyl)phenyl]oxirane (47.0 mg, 0.250 mmol) obtained in Reference Synthetic Example 103 at 80°C for 3 hours. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methanol / chloroform, = 1/20 (v/v)). The resulting solid was washed with hexane / ethyl acetate to give the title compound as a red solid (19.7 mg, yield 42%).

SYNTHETIC EXAMPLES 213 TO 226 The reactions in Synthetic Example 44 were carried out in substantially the same manners except that 2-(4-formylphenoxy)acetonitrile (Reference Synthetic Example 105), 6-chloronicotinaldehyde, (E)(furanyl)acrylaldehyde, 1-methyl-1H-pyrrole carbaldehyde, 3-chloro-1H-indazolecarbaldehyde, quinoxalinecarbaldehyde, oxazolecarbaldehyde, 4-(difluoromethoxy) benzaldehyde, 4-(1H-imidazoleyl) benzaldehyde, 2-fluoroformylbenzonitrile, 2-fluoroformylbenzonitrile, 2,6-difluoro- 4-(trifluoromethyl)benzaldehyde, 3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine carbaldehyde or 4-[(2-cyanoethyl)methylamino]benzaldehyde was used instead of thiazolecarbaldehyde to give the compounds of Synthetic Examples 213 to 226.

The names, morphologies and yields of the synthesized compounds are shown in Table 23.

TABLE 23 Ex Compound Name Morphology Yield 2-(4-{[4-(7H-pyrrolo[3,2-e][1,2,3]tri 213 azolo[1,5-c]pyrimidinyl)piperidin- colorless solid 15% 1-yl]methyl}phenoxy)acetonitrile 1-{1-[(6-chloropyridinyl)methyl]pi 214 peridinyl}-7H-pyrrolo[3,2-e][1,2,3 colorless solid 8% ]triazolo[1,5-c]pyrimidine (E){1-[3-(furanyl)allyl]piperid 215 inyl}-7H-pyrrolo[3,2-e][1,2,3]tria colorless solid 33% zolo[1,5-c]pyrimidine 1-(1-methylpiperidinyl)-7H-pyrrolo 216 [3,2-e][1,2,3]triazolo[1,5-c]pyrimidi yellow solid 27% 1-{1-[(3-chloro-1H-indazolyl)methy 217 l]piperidinyl}-7H-pyrrolo[3,2-e][1 colorless solid 4.0% ,2,3]triazolo[1,5-c]pyrimidine 1-[1-(quinoxalinylmethyl)piperidin 218 yl]-7H-pyrrolo[3,2-e][1,2,3]triazo colorless solid 42% lo[1,5-c]pyrimidine 4-{[4-(7H-pyrrolo[3,2-e][1,2,3]triazo 219 lo[1,5-c]pyrimidinyl)piperidiny colorless solid 23% l]methyl}oxazole 1-{1-[4-(difluoromethoxy)benzyl]piper 220 idinyl}-7H-pyrrolo[3,2-e][1,2,3]tr colorless solid 21% iazolo[1,5-c]pyrimidine 1-{1-[4-(1H-imidazolyl)benzyl]pipe 221 ridinyl}-7H-pyrrolo[3,2-e][1,2,3]t yellow solid 64% riazolo[1,5-c]pyrimidine 4-{[4-(7H-pyrrolo[3,2-e][1,2,3]triazo 222 lo[1,5-c]pyrimidinyl)piperidiny colorless solid 44% l]methyl}fluorobenzonitrile -{[4-(7H-pyrrolo[3,2-e][1,2,3]triazo 223 lo[1,5-c]pyrimidinyl)piperidiny colorless solid 61% l]methyl}fluorobenzonitrile 1-{1-[2,6-difluoro(trifluoromethyl 224 )benzyl]piperidinyl}-7H-pyrrolo[3, colorless solid 26% 2-e][1,2,3]triazolo[1,5-c]pyrimidine 6-{[4-(7H-pyrrolo[3,2-e][1,2,3]triazo lo[1,5-c]pyrimidinyl)piperidiny 225 colorless solid 12% l]methyl}-2H-benzo[b][1,4]oxazin-3(4H )-one 3-[(4-{[4-(7H-pyrrolo[3,2-e][1,2,3]tr iazolo[1,5-c]pyrimidinyl)piperidin 226 colorless solid 5.0% yl]methyl}phenyl)(methyl)amino]pro panenitrile SYNTHETIC EXAMPLE 227 1-{1-[(2,2-Difluorobenzo[d][1,3]dioxolyl)methyl]piperidinyl}-7H-pyrrolo[3,2- e][1,2,3]triazolo[1,5-c]pyrimidine 1-(Piperidinyl)-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine acetate (20.0 mg, 0.0660 mmol) obtained in Reference Synthetic Example 104 in methanol (1 mL) was mixed with 2,2-difluorobenzo[d][1,3]dioxolecarbaldehyde (20.0 µL, 0.0990 mmol), nicotinic acid (12.3 mg, 0.0990 mmol), and 2-picoline borane (10.7 mg, 0.0990 mmol) and stirred at room temperature for 1 day. After addition of 1M aqueous sodium hydroxide, the reaction mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (methanol / chloroform = 1/10 (v/v)) to give the title compound as a colorless solid (13.1 mg, yield 48%).

SYNTHETIC EXAMPLES 228 TO 239 The reactions in Synthetic Example 227 were carried out in substantially the same manners except that 5-chlorofurancarbaldehyde, 2,2- difluorobenzo[d][1,3]dioxolcarbaldehyde, 3-oxophenylpropanenitrile, 2,6- dichloronicotinaldehyde, benzo[d]thiazolecarbaldehyde, 4,5-dibromothiophene carbaldehyde, 2-morpholinothiazolecarbaldehyde, 2-(4-chlorophenyl) oxopropanenitrile, 5-methylthiophenecarbaldehyde, 4-bromothiophene carbaldehyde, 5-bromothiophenecarbaldehyde or isonicotinaldehyde was used instead of 2,2-difluorobenzo[d][1,3]dioxolecarbaldehyde to give the compounds of Synthetic Examples 228 to 239. The names, morphologies and yields of the synthesized compounds are shown in Table 24.

TABLE 24 Ex Compound Name Morphology Yield 1-{1-[(5-chlorofuranyl)methyl]pipe 228 ridinyl}-7H-pyrrolo[3,2-e][1,2,3]t colorless solid 41% riazolo[1,5-c]pyrimidine 1-{1-[(2,2-difluorobenzo[d][1,3]dioxo lyl)methyl]piperidinyl}-7H-pyrr 229 colorless solid 26% olo[3,2-e][1,2,3]triazolo[1,5-c]pyrim idine (Z)[4-(7H-pyrrolo[3,2-e][1,2,3]tri 230 azolo[1,5-c]pyrimidinyl)piperidin- colorless solid 22% 1-yl]phenylacrylonitrile 1-{1-[(2,6-dichloropyridinyl)methy 231 l]piperidinyl}-7H-pyrrolo[3,2-e][1 colorless solid 29% ,2,3]triazolo[1,5-c]pyrimidine 2-{[4-(7H-pyrrolo[3,2-e][1,2,3]triazo 232 lo[1,5-c]pyrimidinyl)piperidiny colorless solid 13% l]methyl}benzo[d]thiazole 1-{1-[(4,5-dibromothiophenyl)methy 233 l]piperidinyl}-7H-pyrrolo[3,2-e][1 colorless solid 40% ,2,3]triazolo[1,5-c]pyrimidine 4-(5-{[4-(7H-pyrrolo[3,2-e][1,2,3]tri 234 azolo[1,5-c]pyrimidinyl)piperidin- colorless solid 13% 1-yl]methyl}thiazolyl)morpholine (Z)[4-(7H-pyrrolo[3,2-e][1,2,3]tri pale purple 235 azolo[1,5-c]pyrimidinyl)piperidin- 5.0% solid 1-yl](4-chlorophenyl)acrylonitrile 1-{1-[(5-methylthiophenyl)methyl]p pale orange 236 iperidinyl}-7H-pyrrolo[3,2-e][1,2, 27% solid 3]triazolo[1,5-c]pyrimidine 1-{1-[(4-bromothiophenyl)methyl]pi 237 colorless solid 8.0% peridinyl}-7H-pyrrolo[3,2-e][1,2,3 ]triazolo[1,5-c]pyrimidine 1-{1-[(5-bromothiophenyl)methyl]pi 238 peridinyl}-7H-pyrrolo[3,2-e][1,2,3 colorless solid 41% ]triazolo[1,5-c]pyrimidine 1-[1-(pyridinylmethyl)piperidin 239 yl]-7H-pyrrolo[3,2-e][1,2,3]triazolo[ colorless solid 39% 1,5-c]pyrimidine SYNTHETIC EXAMPLES 240 TO 246 The reactions in Synthetic Example 32 were carried out in substantially the same manners except that 4-(chloromethyl)thiazole hydrochloride, 4- (bromomethyl)benzamide (Reference Synthetic Example 106), 4- (bromomethyl)phthalonitrile (Reference Synthetic Example 108), 5-(bromomethyl) (trifluoromethyl)benzonitrile (Reference Synthetic Example 107), 4-(bromomethyl) (trifluoromethyl)benzonitrile (Reference Synthetic Example 109), (1- bromoethyl)benzene or 2-chloroacetonitrile was used instead of benzylbromide to give the compounds of Synthetic Examples 240 to 246. The names, morphologies and yields of the synthesized compounds are shown in Table 25.

TABLE 25 Ex Compound Name Morphology Yield 4-{[4-(7H-pyrrolo[3,2-e][1,2,3]triazo 240 lo[1,5-c]pyrimidinyl)piperidiny colorless solid 21% l]methyl}thiazole 4-{[4-(7H-pyrrolo[3,2-e][1,2,3]triazo 241 lo[1,5-c]pyrimidinyl)piperidiny colorless solid 24% l]methyl}benzamide 4-{[4-(7H-pyrrolo[3,2-e][1,2,3]triazo 242 lo[1,5-c]pyrimidinyl)piperidiny colorless solid 71% l]methyl}phthalonitrile -{[4-(7H-pyrrolo[3,2-e][1,2,3]triazo lo[1,5-c]pyrimidinyl)piperidiny 243 colorless solid 77% l]methyl}(trifluoromethyl)benzonit rile 4-{[4-(7H-pyrrolo[3,2-e][1,2,3]triazo lo[1,5-c]pyrimidinyl)piperidiny 244 colorless solid 68% l]methyl}(trifluoromethyl)benzonit rile 1-[1-(1-phenylethyl)piperidinyl]-7 pale purple 245 H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c 6.0% solid ]pyrimidine 2-[4-(7H-pyrrolo[3,2-e][1,2,3]triazol pale purple 246 o[1,5-c]pyrimidinyl)piperidinyl 35% solid ]acetonitrile SYNTHETIC EXAMPLES 247 TO 345 The reactions in Synthetic Example 88 were carried out in substantially the same manners except that 4-aminochlorobenzonitrile, 4-aminonaphthonitrile, 3,4- difluoroaniline, 3,4,5-trifluoroaniline, 4-fluoro(trifluoromethyl)aniline, 5-amino fluorobenzonitrile, 3-aminodihydrothiophen-2(3H)-one hydrochloride, thiazolidine, 2,2- difluoroethaneamine, 3,3,3-trifluoropropaneamine, 3-hydroxyazetidine hydrochloride, 4-(trifluoromethyl)piperidine hydrochloride, 2-aminoacetonitrile hydrochloride, piperazin- 2-one, piperidinecarboxamide, 4-aminophthalonitrile, 5-aminochlorobenzonitrile, 2- (4-aminophenyl)acetonitrile, (R)-pyrrolidineyl methanol, (S)-pyrrolidineyl methanol, (R)-pyrrolidinol, 2-(benzylamino)ethanol, 2-bromo-2,2-difluoroethaneamine hydrochloride (Reference Synthetic Example 131), (4-methoxyphenyl)methanamine, piperidinol, 2-aminoethanol, 7-amino-2H-benzo[b][1,4]oxazine-3(4H)-one, 6-amino- 2H-benzo[b][1,4]oxazine-3(4H)-one, 2,2-difluorobenzo[d][1,3]dioxolamine, (R) aminophenylethanol, (S)aminophenylethanol, azetidinecarboxylic acid, 3- aminodihydrofuran-2(3H)-one hydrobromide, cyclopropylamine, azetidinecarbonitrile hydrochloride, 4-(2-aminoethyl)benzonitrile (Reference Synthetic Example 111), cyclobutanamine, cyclopentanamine, cyclopropylmethanamine, azetidine hydrochloride, pyrrolidine, (R)- 4-aminoisoxazolidinone, (R)-(tetrahydrofuranyl)methanamine, 2,2- dimethylcyclopropanamine hydrochloride, 2-methylcyclopropanamine, 1- (trifluoromethyl)cyclopropanamine, 1-(methoxymethyl)cyclopropanamine hydrochloride, oxetanamine, 1-methylcyclopropanamine hydrochloride, dimethylamine hydrochloride, 2-(methylamino)ethanol, 2,2'-azanediyl diethanol, (R)-tert-butyl pyrrolidin- 3-ylcarbamate, 3-(phenylamino)propanenitrile, (R)-pyrrolidinecarbonitrile hydrochloride, 3-(methylamino)propanenitrile, (1s,3R,4r,5S,7s)aminoadamantanol (Reference Synthetic Example 129), (1s,3R,4s,5S,7s)aminoadamantanol (Reference Synthetic Example 130), transaminocyclohexanol, 2- (cyclohexylamino)ethanol, tert-butyl (S)-pyrrolidinylcarbamate, 3-(4- chlorophenyl)oxetanamine hydrochloride, 4-[4-chloro (trifluoromethyl)phenyl]piperidinol, 4-phenylpiperidinecarbonitrile hydrochloride, 2- (piperidinyl)propanol, cis(aminomethyl)cyclohexanol hydrochloride, 1- (aminomethyl)cyclohexanol hydrochloride, 3-(piperazinyl)propanenitrile, 2-(piperazin- 1-yl)ethanol, bicyclo[1.1.1]pentanamine hydrochloride, 1,1,1,3,3,3-hexafluoropropan- 2-amine, (R)-N-(pyrrolidinyl)acetamide, (S)-N-(pyrrolidinyl)acetamide, (R)-2,2,2- trifluoro-N-(pyrrolidinyl)acetamide hydrochloride, (S)-2,2,2-trifluoro-N-(pyrrolidin yl)acetamide hydrochloride, 3-(4-fluorophenyl)oxetanamine hydrochloride, 1-(4- fluorophenyl)cyclopropanamine hydrochloride, 1-(4-fluorophenyl)cyclobutanamine hydrochloride, 2-methoxy-N-methylethanamine, bis(2-methoxyethyl)amine, (1- aminocyclopropyl)methanol hydrochloride, 3,3-difluoropyrrolidine hydrochloride, methanamine hydrochloride, ethanamine hydrochloride, propanamine, 2- methylpropanamine, propynamine, 4-(piperidinyl)morpholine, tert-butyl 4- (aminomethyl)piperidinecarboxylate, tert-butyl (piperidinylmethyl)carbamate, tert- butyl (S)aminopyrrolidinecarboxylate, 3-fluoroazetidine hydrochloride, 3,3- difluoroazetidine hydrochloride, (R)-N,N-dimethylpyrrolidinamine, 2-amino-N-(2,2,2- trifluoroethyl)acetamide hydrochloride, 2,2,3,3,3-pentafluoropropanamine, 3-amino- 1,1,1-trifluoropropanol, thietanamine hydrobromide or 1-(ethylsulfonyl)piperazine was used instead of thiomorpholine 1,1-dioxide to give the compounds of Synthetic Examples 247 to 345. The names, morphologies and yields of the synthesized compounds are shown in Tables 26 to 33.

TABLE 26 Ex Compound Name Morphology Yield 4-({[trans(7H-pyrrolo[3,2-e][1,2,3 ]triazolo[1,5-c]pyrimidinyl)cycloh 247 colorless solid 79% exyl]methyl}amino)chlorobenzonitri 4-({[trans(7H-pyrrolo[3,2-e][1,2,3 248 ]triazolo[1,5-c]pyrimidinyl)cycloh pale pink solid 56% exyl]methyl}amino)naphthonitrile N-{[trans(7H-pyrrolo[3,2-e][1,2,3] 249 triazolo[1,5-c]pyrimidinyl)cyclohe colorless solid 47% xyl]methyl}-3,4-difluoroaniline N-{[trans(7H-pyrrolo[3,2-e][1,2,3] 250 triazolo[1,5-c]pyrimidinyl)cyclohe colorless solid 65% xyl]methyl}-3,4,5-trifluoroaniline N-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 251 colorless solid 47% xyl]methyl}fluoro(trifluorometh yl)aniline -({[trans(7H-pyrrolo[3,2-e][1,2,3 ]triazolo[1,5-c]pyrimidinyl)cycloh 252 colorless solid 69% exyl]methyl}amino)fluorobenzonitri 3-({[trans(7H-pyrrolo[3,2-e][1,2,3 ]triazolo[1,5-c]pyrimidinyl)cycloh 253 colorless solid 73% exyl]methyl}amino)dihydrothiophen-2(3 H)-one 3-{[trans(7H-pyrrolo[3,2-e][1,2,3] 254 triazolo[1,5-c]pyrimidinyl)cyclohe pale pink solid 21% xyl]methyl}thiazolidine N-{[trans(7H-pyrrolo[3,2-e][1,2,3] pale purple 255 triazolo[1,5-c]pyrimidinyl)cyclohe 62％ solid xyl]methyl}-2,2-difluoroethanamine N-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 256 colorless solid 66% xyl]methyl}-3,3,3-trifluoropropana mine 1-{[trans(7H-pyrrolo[3,2-e][1,2,3] 257 triazolo[1,5-c]pyrimidinyl)cyclohe colorless solid 37% xyl]methyl}azetidinol 1-(trans{[4-(trifluoromethyl)piper idinyl]methyl}cyclohexyl)-7H-pyrro 258 colorless solid 94% lo[3,2-e][1,2,3]triazolo[1,5-c]pyrimi dine 2-({[trans(7H-pyrrolo[3,2-e][1,2,3 259 ]triazolo[1,5-c]pyrimidinyl)cycloh colorless solid 27% exyl]methyl}amino)acetonitrile 4-{[trans(7H-pyrrolo[3,2-e][1,2,3] 260 triazolo[1,5-c]pyrimidinyl)cyclohe colorless solid 52% xyl]methyl}piperazinone TABLE 27 Ex Compound Name Morphology Yield 1-{[trans(7H-pyrrolo[3,2-e][1,2,3] 261 triazolo[1,5-c]pyrimidinyl)cyclohe colorless solid 8.0% xyl]methyl}piperidinecarboxamide 4-({[trans(7H-pyrrolo[3,2-e][1,2,3 262 colorless solid 54% ]triazolo[1,5-c]pyrimidinyl)cycloh exyl]methyl}amino)phthalonitrile -({[trans(7H-pyrrolo[3,2-e][1,2,3 ]triazolo[1,5-c]pyrimidinyl)cycloh 263 colorless solid 75% exyl]methyl}amino)chlorobenzonitri 2-[4-({[trans(7H-pyrrolo[3,2-e][1, 2,3]triazolo[1,5-c]pyrimidinyl)cyc 264 colorless solid 54% lohexyl]methyl}amino)phenyl]acetonitr ((R){[trans(7H-pyrrolo[3,2-e][1 ,2,3]triazolo[1,5-c]pyrimidinyl)cy 265 colorless solid 71% clohexyl]methyl}pyrrolidinyl)metha ((S){[trans(7H-pyrrolo[3,2-e][1 ,2,3]triazolo[1,5-c]pyrimidinyl)cy 266 colorless solid 87% clohexyl]methyl}pyrrolidinyl)metha (R){[trans(7H-pyrrolo[3,2-e][1, 267 2,3]triazolo[1,5-c]pyrimidinyl)cyc colorless solid 68% lohexyl]methyl}pyrrolidinol 2-({[trans(7H-pyrrolo[3,2-e][1,2,3 268 ]triazolo[1,5-c]pyrimidinyl)cycloh colorless solid 62% exyl]methyl}(benzyl)amino)ethanol N-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 269 colorless solid 42% xyl]methyl}bromo-2,2-difluoroethan amine 1-[trans(7H-pyrrolo[3,2-e][1,2,3]t 270 riazolo[1,5-c]pyrimidinyl)cyclohex colorless solid 30% yl]-N-(4-methoxybenzyl)methanamine 1-{[trans(7H-pyrrolo[3,2-e][1,2,3] 271 triazolo[1,5-c]pyrimidinyl)cyclohe colorless solid 54% xyl]methyl}piperidinol 2-({[trans(7H-pyrrolo[3,2-e][1,2,3 272 ]triazolo[1,5-c]pyrimidinyl)cycloh colorless solid 34% exyl]methyl}amino)ethanol 7-({[trans(7H-pyrrolo[3,2-e][1,2,3 ]triazolo[1,5-c]pyrimidinyl)cycloh 273 colorless solid 80% exyl]methyl}amino)-2H-benzo[b][1,4]ox azin-3(4H)-one TABLE 28 Ex Compound Name Morphology Yield 6-({[trans(7H-pyrrolo[3,2-e][1,2,3 ]triazolo[1,5-c]pyrimidinyl)cycloh 274 pale pink solid 98% exyl]methyl}amino)-2H-benzo[b][1,4]ox azin-3(4H)-one N-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 275 colorless solid 63% xyl]methyl}-2,2-difluorobenzo[d][1,3] dioxolamine (R)({[trans(7H-pyrrolo[3,2-e][1 ,2,3]triazolo[1,5-c]pyrimidinyl)cy 276 colorless solid 50% clohexyl]methyl}amino)phenylethano (S)({[trans(7H-pyrrolo[3,2-e][1 ,2,3]triazolo[1,5-c]pyrimidinyl)cy 277 colorless solid 73% clohexyl]methyl}amino)phenylethano 1-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 278 colorless solid 90% xyl]methyl}azetidinecarboxylic acid 3-({[trans(7H-pyrrolo[3,2-e][1,2,3 ]triazolo[1,5-c]pyrimidinyl)cycloh 279 colorless solid quant. exyl]methyl}amino)dihydrofuran-2(3H)- N-{[trans(7H-pyrrolo[3,2-e][1,2,3] 280 triazolo[1,5-c]pyrimidinyl)cyclohe colorless solid 34% xyl]methyl}cyclopropanamine 1-{[trans(7H-pyrrolo[3,2-e][1,2,3] 281 triazolo[1,5-c]pyrimidinyl)cyclohe colorless solid 46% xyl]methyl}azetidinecarbonitrile 4-[2-({[trans(7H-pyrrolo[3,2-e][1, 2,3]triazolo[1,5-c]pyrimidinyl)cyc 282 colorless solid 54% lohexyl]methyl}amino)ethyl]benzonitri N-{[trans(7H-pyrrolo[3,2-e][1,2,3] 283 triazolo[1,5-c]pyrimidinyl)cyclohe colorless solid 70% xyl]methyl}cyclobutanamine N-{[trans(7H-pyrrolo[3,2-e][1,2,3] 284 triazolo[1,5-c]pyrimidinyl)cyclohe colorless solid 63% xyl]methyl}cyclopentanamine 1-[trans(7H-pyrrolo[3,2-e][1,2,3]t 285 riazolo[1,5-c]pyrimidinyl)cyclohex colorless solid 53% yl]-N-(cyclopropylmethyl)methanamine 1-[trans(azetidinylmethyl)cyclo 286 hexyl]-7H-pyrrolo[3,2-e][1,2,3]triazo colorless solid 60% lo[1,5-c]pyrimidine TABLE 29 Ex Compound Name Morphology Yield 1-[trans(pyrrolidinylmethyl)cyc 287 colorless solid 64% lohexyl]-7H-pyrrolo[3,2-e][1,2,3]tria zolo[1,5-c]pyrimidine (R)({[trans(7H-pyrrolo[3,2-e][1 ,2,3]triazolo[1,5-c]pyrimidinyl)cy 288 colorless solid 78% clohexyl]methyl}amino)isoxazolidin 1-[trans(7H-pyrrolo[3,2-e][1,2,3]t riazolo[1,5-c]pyrimidinyl)cyclohex 289 colorless solid 46% yl]-N-{[(R)-tetrahydrofuranyl]meth yl}methanamine N-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 290 colorless solid 44% xyl]methyl}-2,2-dimethylcyclopropanam N-{[trans(7H-pyrrolo[3,2-e][1,2,3] 291 triazolo[1,5-c]pyrimidinyl)cyclohe colorless solid 53% xyl]methyl}methylcyclopropanamine N-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 292 colorless solid 60% xyl]methyl}(trifluoromethyl)cyclop ropanamine N-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 293 colorless solid 52% xyl]methyl}(methoxymethyl)cyclopro panamine N-{[trans(7H-pyrrolo[3,2-e][1,2,3] 294 triazolo[1,5-c]pyrimidinyl)cyclohe colorless solid 40% xyl]methyl}oxetanamine N-{[trans(7H-pyrrolo[3,2-e][1,2,3] 295 triazolo[1,5-c]pyrimidinyl)cyclohe colorless solid 25% xyl]methyl}methylcyclopropanamine 1-[trans(7H-pyrrolo[3,2-e][1,2,3]t 296 riazolo[1,5-c]pyrimidinyl)cyclohex colorless solid 43% yl]-N,N-dimethylmethanamine 2-({[trans(7H-pyrrolo[3,2-e][1,2,3 297 ]triazolo[1,5-c]pyrimidinyl)cycloh colorless solid 57% exyl]methyl}(methyl)amino)ethanol 2,2'-({[trans(7H-pyrrolo[3,2-e][1, 298 2,3]triazolo[1,5-c]pyrimidinyl)cyc colorless solid 43% lohexyl]methyl}azanediyl)diethanol tert-butyl ((R){[trans(7H-pyrrolo[3,2-e][1 299 ,2,3]triazolo[1,5-c]pyrimidinyl)cy colorless solid 64% clohexyl]methyl}pyrrolidinyl)carba mate TABLE 30 Ex Compound Name Morphology Yield 3-({[trans(7H-pyrrolo[3,2-e][1,2,3 ]triazolo[1,5-c]pyrimidinyl)cycloh 300 colorless solid 72% exyl]methyl}(phenyl)amino)propanenitr (R){[trans(7H-pyrrolo[3,2-e][1, 2,3]triazolo[1,5-c]pyrimidinyl)cyc 301 colorless solid 58% lohexyl]methyl}pyrrolidinecarbonit rile 3-({[trans(7H-pyrrolo[3,2-e][1,2,3 ]triazolo[1,5-c]pyrimidinyl)cycloh 302 colorless solid 42% exyl]methyl}(methyl)amino)propanenitr (1S,3R,4r,5S,7S)({[trans(7H-pyr rolo[3,2-e][1,2,3]triazolo[1,5-c]pyri 303 colorless solid 61% midinyl)cyclohexyl]methyl}amino)ad amantanol (1S,3R,4s,5S,7S)({[trans(7H-pyr rolo[3,2-e][1,2,3]triazolo[1,5-c]pyri 304 colorless solid 53% midinyl)cyclohexyl]methyl}amino)ad amantanol trans({[trans(7H-pyrrolo[3,2-e] 305 [1,2,3]triazolo[1,5-c]pyrimidinyl) colorless solid 35% cyclohexyl]methyl}amino)cyclohexanol 2-({[trans(7H-pyrrolo[3,2-e][1,2,3 306 ]triazolo[1,5-c]pyrimidinyl)cycloh colorless solid 40% exyl]methyl}(cyclohexyl)amino)ethanol tert-butyl ((S){[trans(7H-pyrrolo[3,2-e][1 307 ,2,3]triazolo[1,5-c]pyrimidinyl)cy colorless solid 69% clohexyl]methyl}pyrrolidinyl)carba mate N-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 308 colorless solid 72% xyl]methyl}(4-chlorophenyl)oxetan- 3-amine 1-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 309 colorless solid 54% xyl]methyl}[4-chloro(trifluorom ethyl)phenyl]piperidinol 1-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 310 colorless solid 56% xyl]methyl}phenylpiperidinecarb onitrile 2-(1-{[trans(7H-pyrrolo[3,2-e][1,2 ,3]triazolo[1,5-c]pyrimidinyl)cycl 311 colorless solid 59% ohexyl]methyl}piperidinyl)propan-2 TABLE 31.

Ex Compound Name Morphology Yield cis[({[trans(7H-pyrrolo[3,2-e][ 1,2,3]triazolo[1,5-c]pyrimidinyl)c 312 colorless solid 14% yclohexyl]methyl}amino)methyl]cyclohe xanol 1-[({[trans(7H-pyrrolo[3,2-e][1,2, 3]triazolo[1,5-c]pyrimidinyl)cyclo 313 colorless solid 47% hexyl]methyl}amino)methyl]cyclohexano 3-(4-{[trans(7H-pyrrolo[3,2-e][1,2 ,3]triazolo[1,5-c]pyrimidinyl)cycl 314 colorless solid 35% ohexyl]methyl}piperazinyl)propanen itrile 2-(4-{[trans(7H-pyrrolo[3,2-e][1,2 315 ,3]triazolo[1,5-c]pyrimidinyl)cycl colorless solid 35% ohexyl]methyl}piperazinyl)ethanol N-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 316 colorless solid 44% xyl]methyl}bicyclo[1.1.1]pentanami N-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 317 colorless solid 77% xyl]methyl}-1,1,1,3,3,3-hexafluoropro panamine N-((R){[trans(7H-pyrrolo[3,2-e] [1,2,3]triazolo[1,5-c]pyrimidinyl) 318 colorless solid 48% cyclohexyl]methyl}pyrrolidinyl)ace tamide N-((S){[trans(7H-pyrrolo[3,2-e] [1,2,3]triazolo[1,5-c]pyrimidinyl) 319 colorless solid 29% cyclohexyl]methyl}pyrrolidinyl)ace tamide N-((R){[trans(7H-pyrrolo[3,2-e] [1,2,3]triazolo[1,5-c]pyrimidinyl) 320 colorless solid 49% cyclohexyl]methyl}pyrrolidinyl)-2, 2,2-trifluoroacetamide N-((S){[trans(7H-pyrrolo[3,2-e] [1,2,3]triazolo[1,5-c]pyrimidinyl) 321 colorless solid 48% cyclohexyl]methyl}pyrrolidinyl)-2, 2,2-trifluoroacetamide N-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 322 colorless solid 52% xyl]methyl}(4-fluorophenyl)oxetan- 3-amine N-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 323 colorless solid 39% xyl]methyl}(4-fluorophenyl)cyclopr opanamine TABLE 32 Ex Compound Name Morphology Yield N-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 324 colorless solid 39% xyl]methyl}(4-fluorophenyl)cyclobu tanamine N-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 325 colorless solid 71% xyl]methyl}methoxy-N-methylethanam N-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 326 colorless solid 76% xyl]methyl}methoxy-N-(2-methoxyeth yl)ethanamine [1-({[trans(7H-pyrrolo[3,2-e][1,2, 3]triazolo[1,5-c]pyrimidinyl)cyclo 327 colorless solid 58% hexyl]methyl}amino)cyclopropyl]methan 1-{trans[(3,3-difluoropyrrolidin-1 328 colorless solid 26% -yl)methyl]cyclohexyl}-7H-pyrrolo[3,2 -e][1,2,3]triazolo[1,5-c]pyrimidine 1-[trans(7H-pyrrolo[3,2-e][1,2,3]t 329 riazolo[1,5-c]pyrimidinyl)cyclohex colorless solid 26% yl]-N-methylmethanamine N-{[trans(7H-pyrrolo[3,2-e][1,2,3] 330 colorless solid 58% triazolo[1,5-c]pyrimidinyl)cyclohe xyl]methyl}ethanamine N-{[trans(7H-pyrrolo[3,2-e][1,2,3] 331 triazolo[1,5-c]pyrimidinyl)cyclohe colorless solid 55% xyl]methyl}propanamine N-{[trans(7H-pyrrolo[3,2-e][1,2,3] 332 triazolo[1,5-c]pyrimidinyl)cyclohe colorless solid 34% xyl]methyl}methylpropanamine N-{[trans(7H-pyrrolo[3,2-e][1,2,3] 333 triazolo[1,5-c]pyrimidinyl)cyclohe colorless solid 62% xyl]methyl}propynamine 4-(1-{[trans(7H-pyrrolo[3,2-e][1,2 ,3]triazolo[1,5-c]pyrimidinyl)cycl 334 colorless solid 44% ohexyl]methyl}piperidinyl)morpholi tert-butyl 4-[({[trans(7H-pyrrolo[3,2-e][1,2, 335 3]triazolo[1,5-c]pyrimidinyl)cyclo colorless solid 17% hexyl]methyl}amino)methyl]piperidine- 1-carboxylate tert-butyl [(1-{[trans(7H-pyrrolo[3,2-e][1,2, 336 3]triazolo[1,5-c]pyrimidinyl)cyclo colorless solid 3.0% hexyl]methyl}piperidinyl)methyl]ca rbamate TABLE 33 Ex Compound Name Morphology Yield (S)-tert-butyl 3-({[trans(7H-pyrrolo[3,2-e][1,2,3 337 ]triazolo[1,5-c]pyrimidinyl)cycloh colorless solid 10% exyl]methyl}amino)pyrrolidinecarbo xylate 1-{trans[(3-fluoroazetidinyl)me 338 thyl]cyclohexyl}-7H-pyrrolo[3,2-e][1, colorless solid 33% 2,3]triazolo[1,5-c]pyrimidine 1-{trans[(3,3-difluoroazetidiny 339 l)methyl]cyclohexyl}-7H-pyrrolo[3,2-e colorless solid 35% ][1,2,3]triazolo[1,5-c]pyrimidine (R){[trans(7H-pyrrolo[3,2-e][1, 2,3]triazolo[1,5-c]pyrimidinyl)cyc 340 colorless solid 87% lohexyl]methyl}-N,N-dimethylpyrrolidi namine 2-({[trans(7H-pyrrolo[3,2-e][1,2,3 ]triazolo[1,5-c]pyrimidinyl)cycloh 341 colorless solid 63% exyl]methyl}amino)-N-(2,2,2-trifluoro ethyl)acetamide N-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 342 colorless solid 74% xyl]methyl}-2,2,3,3,3-pentafluoroprop anamine 3-({[trans(7H-pyrrolo[3,2-e][1,2,3 ]triazolo[1,5-c]pyrimidinyl)cycloh 343 colorless solid 66% exyl]methyl}amino)-1,1,1-trifluoropro panol N-{[trans(7H-pyrrolo[3,2-e][1,2,3] 344 triazolo[1,5-c]pyrimidinyl)cyclohe colorless solid 58% xyl]methyl}thietanamine 1-(trans{[4-(ethylsulfonyl)piperaz inyl]methyl}cyclohexyl)-7H-pyrrolo 345 colorless solid 71% [3,2-e][1,2,3]triazolo[1,5-c]pyrimidi SYNTHETIC EXAMPLE 346 trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)-N-(3,3,3-trifluoro hydroxyphenylpropyl)cyclohexanecarboxamide trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexanecarboxylic acid (10.0 mg, 0.0350 mmol) obtained in Synthetic Example 80 in N,N- dimethylformamide (1 mL) was mixed with 1-(3-dimethylaminopropyl) ethylcarbodiimide hydrochloride (8.10 mg, 0.0420 mmol), 1-hydroxybenzotriazole (4.70 mg, 0.0350 mmol) and 3-amino-1,1,1-trifluorophenylpropanol (7.20 mg, 0.0350 mmol) obtained in Reference Synthetic Example 101 and stirred at room temperature for one day. After addition of saturated aqueous ammonium chloride, the reaction mixture was extracted with ethyl acetate, The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (ethyl acetate / hexane = 1/1(v/v)) to give the title compound as a colorless solid (5.80 mg, yield 35%).

SYNTHETIC EXAMPLE 347 trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)-N-[3,3,3-trifluoro(4- fluorophenyl)hydroxypropyl]cyclohexanecarboxamide The reactions in Synthetic Example 346 were carried out in substantially the same manners except that 3-amino-1,1,1-trifluoro(4-fluorophenyl)propanol obtained in Reference Synthetic Example 102 was used instead of 3-amino-1,1,1- trifluorophenylpropanol to give the title compound as a colorless solid (7.37 mg, yield 43%).

SYNTHETIC EXAMPLE 348 TO 363 The reactions in Synthetic Example 206 were carried out in substantially the same manners except that ammonium chloride, 5-methylfurfurylamine, 4- (aminomethyl)benzonitrile hydrochloride, 2-phenylglycinonitrile hydrochloride, 2-(4- chlorophenyl)ethylamine, (S)aminophenylethanol, 2,2,2-trifluoroethylamine hydrochloride, 2-aminoacetonitrile hydrochloride, 3-aminopropionitrile, (S)-pyrrolidine carbonitrile, (S)-pyrrolidineol, cyclopropylamine, 2-aminoethanol, 3-hydroxyazetidine hydrochloride, 4-(2-aminoethyl)benzonitrile or azetidinecarbonitrile hydrochloride was used instead of 4-fluoroaniline to give the compounds of Synthetic Examples 348 to 363. The names, morphologies and yields of the synthesized compounds are shown in Tables 34 to 35.

TABLE 34 Ex Compound Name Morphology Yield trans(7H-pyrrolo[3,2-e][1,2,3]tria 348 zolo[1,5-c]pyrimidinyl)cyclohexane colorless solid 87% carboxamide trans-N-[(5-methylfuranyl)methyl]- 4-(7H-pyrrolo[3,2-e][1,2,3]triazolo[1 349 colorless solid 69% ,5-c]pyrimidinyl)cyclohexanecarbox amide trans-N-(4-cyanobenzyl)(7H-pyrrolo 350 [3,2-e][1,2,3]triazolo[1,5-c]pyrimidi colorless solid 57% nyl)cyclohexanecarboxamide trans-N-[cyano(phenyl)methyl](7H-p 351 yrrolo[3,2-e][1,2,3]triazolo[1,5-c]py colorless solid 58% rimidinyl)cyclohexanecarboxamide trans-N-(4-chlorophenethyl)(7H-pyr pale yellow 352 rolo[3,2-e][1,2,3]triazolo[1,5-c]pyri 68% solid midinyl)cyclohexanecarboxamide trans-N-[(S)hydroxyphenylethyl] (7H-pyrrolo[3,2-e][1,2,3]triazolo[ 353 colorless solid 40% 1,5-c]pyrimidinyl)cyclohexanecarbo xamide TABLE 35 Ex Compound Name Morphology Yield trans(7H-pyrrolo[3,2-e][1,2,3]tria 354 zolo[1,5-c]pyrimidinyl)-N-(2,2,2-t colorless solid 54% rifluoroethyl)cyclohexanecarboxamide trans-N-(cyanomethyl)(7H-pyrrolo[3 355 ,2-e][1,2,3]triazolo[1,5-c]pyrimidin- pale brown solid 27% 1-yl)cyclohexanecarboxamide trans-N-(2-cyanoethyl)(7H-pyrrolo[ 356 3,2-e][1,2,3]triazolo[1,5-c]pyrimidin colorless solid 29% yl)cyclohexanecarboxamide (S)[trans(7H-pyrrolo[3,2-e][1,2 ,3]triazolo[1,5-c]pyrimidinyl)cycl 357 colorless solid 17% ohexanecarbonyl]pyrrolidinecarboni trile [trans(7H-pyrrolo[3,2-e][1,2,3]tri azolo[1,5-c]pyrimidinyl)cyclohexyl 358 colorless solid 18% ][(S)hydroxypyrrolidinyl]methan trans-N-cyclopropyl(7H-pyrrolo[3,2 pale yellow 359 -e][1,2,3]triazolo[1,5-c]pyrimidin 33% solid yl)cyclohexanecarboxamide trans-N-(2-hydroxyethyl)(7H-pyrrol 360 o[3,2-e][1,2,3]triazolo[1,5-c]pyrimid pale brown solid 15% inyl)cyclohexanecarboxamide [trans(7H-pyrrolo[3,2-e][1,2,3]tri 361 azolo[1,5-c]pyrimidinyl)cyclohexyl colorless solid 87% ](3-hydroxyazetidinyl)methanone trans-N-(4-cyanophenethyl)(7H-pyrr 362 olo[3,2-e][1,2,3]triazolo[1,5-c]pyrim colorless solid 12% idinyl)cyclohexanecarboxamide 1-[trans(7H-pyrrolo[3,2-e][1,2,3]t 363 riazolo[1,5-c]pyrimidinyl)cyclohex colorless solid 20% anecarbonyl]azetidinecarbonitrile SYNTHETIC EXAMPLES 364 TO 366 The reactions in Synthetic Example 77 were carried out in substantially the same manners except that sodium benzene sulfinate, sodium 4-fluorobenzenesulfinate or sodium cyclopropanesulfinate was used instead of sodium methanesulfinate to give the compounds of Synthetic Examples 364 to 366. The names, morphologies and yields of the synthesized compounds are shown in Table 36.

TABLE 36 Ex Compound Name Morphology Yield 1-{trans[(phenylsulfonyl)methyl]cy 364 clohexyl}-7H-pyrrolo[3,2-e][1,2,3]tri colorless solid 30% azolo[1,5-c]pyrimidine 1-(trans{[(4-fluorophenyl)sulfonyl 365 colorless solid 36% ]methyl}cyclohexyl)-7H-pyrrolo[3,2-e] [1,2,3]triazolo[1,5-c]pyrimidine 1-{trans[(cyclopropylsulfonyl)meth 366 yl]cyclohexyl}-7H-pyrrolo[3,2-e][1,2, colorless solid 30% 3]triazolo[1,5-c]pyrimidine SYNTHETIC EXAMPLE 367 1-[trans(Iodomethyl)cyclohexyl]-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine 2,3-Dichloro-5,6-dicyano-p-benzoquinone (50.0 mg, 0.221 mmol) and triphenylphosphine (58.0 mg, 0.221 mmol) in dichloromethane (3 mL) were mixed with tetrabutylammonium iodide (81.7 mg, 0.221mmol) and [trans(7H-pyrrolo[3,2- e][1,2,3]triazolo[1,5-c]pyirimidinyl)cyclohexyl]methanol (50.0 mg, 0.184 mmol) obtained in Synthetic Example 10 and then was stirred at 40°C for 8 hours. After addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1/1 → 3/2 (v/v)) to give the title compound as a colorless solid (51.9 mg, yield 74%).

SYNTHETIC EXAMPLE 368 1-(trans{[(Trifluoromethyl)sulfonyl]methyl}cyclohexyl)-7H-pyrrolo[3,2- e][1,2,3]triazolo[1,5-c]pyrimidine 1-[trans(Iodomethyl)cyclohexyl]-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine (50.0 mg, 0.131 mmol) and sodium trifluoromethylsulfinate (205 mg, 1.31 mmol) in N,N- dimethylformamide(3 mL) were stirred at 100°C for 26 hours. After addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer washed with saturated aqueous sodium hydrogen carbonate, saturated aqueous ammonium chloride and saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 3/2 → 1/1(v/v)) and preparative HPLC (Waters XBridge Prep C18µm ODS, 19×100mm, acetonitrile / 0.1% aqueous formic acid solution = 20/80 → 80/20(v/v)) to give the title compound as a colorless solid (6.30 mg, yield 12%).

SYNTHETIC EXAMPLE 369 1-[trans(Azidomethyl)cyclohexyl]-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine 1-[trans(Bromomethyl)cyclohexyl]-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5- c]pyrimidine (50.0 mg, 0.150 mmol) obtained in Synthetic Example 74 in tetrahydrofurane (2 mL) was mixed with trimethylsilylazide (39.0 µL, 0.299 mmol) and tetrabutylammonium fluoride - tetrahydrofuran solution (1 M, 299 µL, 0.299 mmol) and then stirred at 50°C for 3 hours. After addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was washed with ethyl acetate / hexane (1/5 (v/v)) to give the title compound as a colorless solid (30.6 mg, yield 69%).

SYNTHETIC EXAMPLE 370 2-(1-{[trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]methyl}- 1H-1,2,3-triazolyl)propanol 1-[trans(Azidomethyl)cyclohexyl]-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5- c]pyrimidine (30.0 mg, 0.101 mmol) and 2-methylbutynol (12.0 µL, 0.122 mmol) in dichloromethane (3 mL) were mixed with copper(II) sulfate (24.0 mg, 0.152 mmol) and sodium ascorbate (60.0 mg, 0.304 mmol) and then stirred at 80°C for 2 hours. After addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 4/1 → 0/1 →ethyl acetate / methanol=20/1 (v/v)) to give the title compound as a colorless solid (13.2 mg, yield 34%).

SYNTHETIC EXAMPLE 371 [trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]methanamine 1-[trans(Azidomethyl)cyclohexyl]-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5- c]pyrimidine (127 mg, 0.427 mmol) obtained in Synthetic Example 369 and 5% palladium-carbon (12.7 mg) in methanol (3 mL) and dichloromethane (3 mL) were stirred at room temperature for 4 hours under a hydrogen atmosphere. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / methanol=1/0 → 10/1 (v/v/) to give the title compound as a colorless solid (95.0 mg, yield 82%).

SYNTHETIC EXAMPLE 372 N-{[trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]methyl} cyanoacetamide [trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexyl]methanamine (40.0 mg, 0.148 mmol), 2-cyanoacetic acid (15.0 mg, 0.178 mmol) and O-(7-azabenzotriazolyl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (68.0 mg, 0.178 mmol) in N,N-dimethylformamide (2 mL) were mixed with N,N-diisopropylethylamine (57.0 µL, 0.326 mmol) and stirred at room temperature for 16 hours. After addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / acetone = 1/1 → 2/3 (v/v)) to give the title compound as a colorless solid (11.4 mg, yield 23%).

SYNTHETIC EXAMPLE 373 40 N-{[trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]methyl}- 3,3,3-trifluoropropanamide The reactions in Synthetic Example 372 were carried out in substantially the same manners except that 3,3,3-trifluoropropanoic acid was used instead of 2- cyanoacetic acid to give the title compound as a colorless solid (5.00 mg, yield 12%). 45 SYNTHETIC EXAMPLE 374 1-{1-[(3-Chloromethyl(2,2,2-trifluoroethyl)-1H-pyrazolyl)methyl]piperidinyl}- 7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine 3-Chloromethyl-1H-pyrazolecarbaldehyde (100 mg, 0.692 mmol) in N,N- dimethylformamide (2 mL) was mixed with potassium carbonate (287 mg, 2.08 mmol) and 2,2,2-trifluoroethyl trifluoromethanesulfonate (200 µL, 1.38 mmol) and stirred at room temperature for 1 day. After addition of saturated aqueous ammonium chloride, the reaction mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue and 1-(piperidinyl)-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine acetate (20.0 mg, 0.0660 mmol) obtained in Reference Synthetic Example 104 were dissolved in methanol (1 mL) and mixed with nicotinic acid (12.3 mg, 0.0990 mmol) and 2-picoline borane (10.7 mg, 0.0990 mmol). The reaction mixture was stirred at room temperature for 1 day. After addition of 1 M aqueous sodium hydroxide, the reaction mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (methanol / chloroform = 1/10 (v/v)) to give the title compound as a colorless solid (2.35 mg, yield 8%).

SYNTHETIC EXAMPLE 375 4-{2-[4-(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)piperidin yl]ethyl}benzonitrile The reactions in Synthetic Example 32 were carried out in substantially the same manners except that 4-cyanophenethyl 4-methylbenzenesulfonate (Reference Synthetic Example 132) was used instead of benzyl bromide to give the title compound as a colorless solid (7.03mg, yield 29%).

SYNTHETIC EXAMPLE 376 4-[4-(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)piperidinyl]benzonitrile 1-(Piperidinyl)-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine acetate (30.0 mg, 0.0992 mmol) obtained in Reference Synthetic Example 104 in N,N-dimethylformamide (1 mL) was mixed with 4-fluorobenzonitrile (18.0 mg, 0.149 mmol) and potassium carbonate (27.4 mg, 0.198 mmol) and then stirred at 80°C for 31 hours. After addition of water, the reaction mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (methanol / chloroform = 1/19 (v/v)) to give the title compound as a colorless solid (0.520mg, yield 2%).

SYNTHETIC EXAMPLE 377 4-{[4-(9-Chloro-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)piperidin yl]methyl}benzonitrile 4-{[4-(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)piperidin yl]methyl}benzonitrile (20.0 mg, 0.0660 mmol) obtained in Synthetic Example 34 in N,N-dimethylformamide (1 mL) was mixed with N-chlorosuccinimide (10.7 mg, 0.0990 mmol) and stirred at room temperature for 1 day. After addition of 1M aqueous sodium 40 hydroxide, the reaction mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (methanol / chloroform = 1/10 (v/v)) to give the title compound as a colorless solid (13.1 mg, yield 48%).

SYNTHETIC EXAMPLES 378 TO 380 45 The reactions in Synthetic Example 121 were carried out in substantially the same manners except that (1R,2S)amino-2,3-dihydro-1H-indenol, (1S,2R) amino-2,3-dihydro-1H-indenol or 3,3'-azanediyldipropanenitrile was used instead of 4-aminobenzonitrile to give cis/trans mixture of the compounds of Synthetic Examples 378 to 380. The names, morphologies and yields of the compounds synthesized are shown in Table 37.

TABLE 37 SYNTHETIC EXAMPLES 381 TO 384 The reactions in Synthetic Example 136 were carried out in substantially the same manners except that 4-fluoroaniline, 2-bromo-2,2-difluoroethanamine hydrochloride (Reference Synthetic Example 131), 2,2,3,3,3-pentafluoropropylamine or 2-amino-N-(2,2,2-trifluoroethyl)acetamide was used instead of 3-phenylpropanamine to give the compounds of Synthetic Examples 381a to 384a in less polar fractions and the compounds of Synthetic Examples 381b to 384b in more polar fractions. The names, morphologies and yields of the compounds synthesized are shown in Table 38.

TABLE 38 Ex Compound Name Morphology Yield N-[cis(7H-pyrrolo[3,2-e][1,2,3]tri pale yellow 381a azolo[1,5-c]pyrimidinyl)cyclohexyl 11% solid ]fluoroaniline N-[trans(7H-pyrrolo[3,2-e][1,2,3]t pale yellow 381b 13% riazolo[1,5-c]pyrimidinyl)cyclohex solid yl]fluoroaniline cis-N-(2-bromo-2,2-difluoroethyl)( 382a 7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5- colorless solid 1.0% c]pyrimidinyl)cyclohexanamine trans-N-(2-bromo-2,2-difluoroethyl)-4 382b -(7H-pyrrolo[3,2-e][1,2,3]triazolo[1, colorless solid 4.0% -c]pyrimidinyl)cyclohexanamine cis-N-(2,2,3,3,3-pentafluoropropyl)-4 383a -(7H-pyrrolo[3,2-e][1,2,3]triazolo[1, colorless solid 12% -c]pyrimidinyl)cyclohexanamine trans-N-(2,2,3,3,3-pentafluoropropyl) 383b (7H-pyrrolo[3,2-e][1,2,3]triazolo[ colorless solid 29% 1,5-c]pyrimidinyl)cyclohexanamine 2-{[cis(7H-pyrrolo[3,2-e][1,2,3]tr iazolo[1,5-c]pyrimidinyl)cyclohexy 384a colorless solid 11% l]amino}-N-(2,2,2-trifluoroethyl)acet amide 2-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 384b colorless solid 27% xyl]amino}-N-(2,2,2-trifluoroethyl)ac etamide SYNTHETIC EXAMPLES 385 TO 400 The reactions in Synthetic Example 136 were carried out in substantially the same manners except that 3-amino-1,1,1-trifluoro(pyridinyl)propanol, 3-amino- 1,1,1-trifluoro[4-(methylthio)phenyl]propanol, 3-amino-1,1,1-trifluoro(6- methoxypyridinyl)propanol, 3-amino-1,1,1-trifluoro(4-methoxyphenyl)propan ol, [trans(4-fluorophenyl)cyclopropyl]methanamine, 3-amino(3,4- dimethoxyphenyl)-1,1,1-trifluoropropanol, 4-(2-aminoethyl)benzonitrile, cyclopropylamine, 2-aminoacetonitrile hydrochloride, 3-aminopropanenitrile, 2,2,2- trifluoroethanamine hydrochloride, cyclopropylmethanamine, dimethylamine (2M solution in tetrahydrofuran), methanamine (2M solution in methanol), 2,2- difluoroethanamine or 1,1,1,3,3,3,-hexafluoropropanamine was used instead of 3- phenylpropanamine to give the compounds of Synthetic Examples 385b to 400b in more polar fractions. The names, morphologies and yields of the compounds synthesized are shown in Tables 39 to 40.

TABLE 39 Ex Compound Name Morphology Yield 3-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 385b colorless solid 30% xyl]amino}-1,1,1-trifluoro(pyridin yl)propanol 3-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 386b colorless solid 31% xyl]amino}-1,1,1-trifluoro[4-(meth ylthio)phenyl]propanol 3-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 387b colorless solid 26% xyl]amino}-1,1,1-trifluoro(6-metho xypyridinyl)propanol 3-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 388b colorless solid 38% xyl]amino}-1,1,1-trifluoro(4-metho xyphenyl)propanol trans-N-{[trans(4-fluorophenyl)cyc lopropyl]methyl}(7H-pyrrolo[3,2-e] 389b colorless solid 16% [1,2,3]triazolo[1,5-c]pyrimidinyl) cyclohexanamine 3-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 390b colorless solid 12% xyl]amino}(3,4-dimethoxyphenyl)-1, 1,1-trifluoropropanol 4-(2-{[trans(7H-pyrrolo[3,2-e][1,2 391b ,3]triazolo[1,5-c]pyrimidinyl)cycl colorless solid 12% ohexyl]amino}ethyl)benzonitrile trans-N-cyclopropyl(7H-pyrrolo[3,2 392b -e][1,2,3]triazolo[1,5-c]pyrimidin colorless solid 26% yl)cyclohexanamine 2-{[trans(7H-pyrrolo[3,2-e][1,2,3] pale yellow 393b triazolo[1,5-c]pyrimidinyl)cyclohe 15% solid xyl]amino}acetonitrile 3-{[trans(7H-pyrrolo[3,2-e][1,2,3] pale yellow 394b triazolo[1,5-c]pyrimidinyl)cyclohe 8.0% solid xyl]amino}propanenitrile trans(7H-pyrrolo[3,2-e][1,2,3]tria 395b zolo[1,5-c]pyrimidinyl)-N-(2,2,2-t colorless solid 15% rifluoroethyl)cyclohexanamine trans-N-(cyclopropylmethyl)(7H-pyr 396b rolo[3,2-e][1,2,3]triazolo[1,5-c]pyri pale brown solid 40% midinyl)cyclohexanamine trans-N,N-dimethyl(7H-pyrrolo[3,2- pale yellow 397b e][1,2,3]triazolo[1,5-c]pyrimidiny 27% solid l)cyclohexanamine TABLE 40 Ex Compound Name Morphology Yield trans-N-methyl(7H-pyrrolo[3,2-e][1 398b ,2,3]triazolo[1,5-c]pyrimidinyl)cy colorless solid 19% clohexanamine trans-N-(2,2-difluoroethyl)(7H-pyr pale yellow 399b rolo[3,2-e][1,2,3]triazolo[1,5-c]pyri 20% solid midinyl)cyclohexanamine trans-N-(1,1,1,3,3,3-hexafluoropropan yl)(7H-pyrrolo[3,2-e][1,2,3]tri 400b colorless solid 7.0% azolo[1,5-c]pyrimidinyl)cyclohexan amine SYNTHETIC EXAMPLE 401 [cis(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]methanol The reactions in Synthetic Example 141 were carried out in substantially the same manners except that 1-(cis{[(tert-butyldimethylsilyl)oxy]methyl}cyclohexyl)-7H- pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine (Reference Synthetic Example 135a) was used instead of 1-(trans{[(tert-butyldimethylsilyl)oxy]methyl}cyclohexyl)-7H- pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine to give the title compound as a pale pink solid (297 mg, yield 57%).

SYNTHETIC EXAMPLE 402 cis(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexanecarbaldehyde The reactions in Synthetic Example 78 were carried out in substantially the same manners except that [cis(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexyl]methanol was used instead of [trans(7H-pyrrolo[3,2- e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]methanol to give the title compound as a colorless solid (192 mg, yield 88%).

SYNTHETIC EXAMPLE 403 1-{[cis(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]methyl}azetidin- 3-ol cis(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexanecarbaldehyde (30.0 mg, 0.111 mmol) in methanol (2 mL), tetrahydrofuran (1 mL) and acetic acid (100 µL) was mixed with 3-hydroxyazetidine hydrochloride (41.3 mg, 0.334 mmol) and stirred at room temperature for 1 hour. The reaction mixture was mixed with 2-picoline borane (23.8 mg, 0.334 mmol) and stirred at room temperature for 14 hours. After addition of water, the reaction mixture was extracted with ethyl acetate.

The aqueous layer was adjusted to pH 10 with 1 M aqueous sodium hydroxide, and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was washed with hexane / ethyl acetate (5/1 (v/v)) to give the title compound as a colorless solid (7.40 mg, yield 31%).

SYNTHETIC EXAMPLES 404 TO 406 The reactions in Synthetic Example 403 were carried out in substantially the same manners except that (S)-pyrrolidinol hydrochloride, (R)-pyrrolidinol hydrochloride or cyclopropylamine hydrochloride (Reference Synthetic Example 136) was used instead of 3-hydroxyazetidine hydrochloride to give the compounds of Synthetic Examples 404 to 406. The names, morphologies and yields of the compounds synthesized are shown in Table 41.

TABLE 41 Ex Compound Name Morphology Yield (S){[cis(7H-pyrrolo[3,2-e][1,2, 404 3]triazolo[1,5-c]pyrimidinyl)cyclo colorless solid 96% hexyl]methyl}pyrrolidinol (R){[cis(7H-pyrrolo[3,2-e][1,2, 405 3]triazolo[1,5-c]pyrimidinyl)cyclo colorless solid 55% hexyl]methyl}pyrrolidinol N-{[cis(7H-pyrrolo[3,2-e][1,2,3]tr 406 iazolo[1,5-c]pyrimidinyl)cyclohexy colorless solid 16% l]methyl}cyclopropanamine SYNTHETIC EXAMPLE 407 N-{[trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]methyl} cyano-N-(2,2,2-trifluoroethyl)acetamide N-{[trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexyl]methyl}-2,2,2-trifluoroethanamine (20.0 mg, 0.0567 mmol) obtained in Synthetic Example 188 in N,N-dimethylformamide (1 mL) was mixed with 2- cyanoacetic acid (9.60 mg, 0.113 mmol) and O-(7-azabenzotriazolyl)-N,N,N',N'- tetramethyluronium hexafluorophosphate (45.0 mg, 0.113 mmol) and stirred with N,N- diisopropylethylamine (0.0346 mL, 0.198 mmol) at room temperature for 2 hours. After addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1/1 → 6/1 (v/v)) to give the title compound as a colorless solid (23.6 mg, yield 99%).

SYNTHETIC EXAMPLES 408 TO 410 The reactions in Synthetic Example 407 were carried out in substantially the same manners except that 2-({[trans(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin- 1-yl)cyclohexyl]methyl}amino)acetonitrile (Synthetic Example 259), N-{[trans(7H- pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]methyl}cyclopropanamine (Synthetic Example 280) or 1-[trans(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin- 1-yl)cyclohexyl]-N-[(5-methylfuranyl)methyl]methanamine (Synthetic Example 182) was used instead of N-{[trans(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexyl]methyl}-2,2,2-trifluoroethanamine to give the compounds of Synthetic Examples 408 to 410. The names, morphologies and yields of the compounds synthesized are shown in Table 42.

TABLE 42 Ex Compound Name Morphology Yield N-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 408 colorless solid 53% xyl]methyl}cyano-N-(cyanomethyl)ac etamide N-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 409 colorless solid 93% xyl]methyl}cyano-N-cyclopropylacet amide N-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 410 gray solid 83% xyl]methyl}cyano-N-[(5-methylfuran yl)methyl]acetamide SYNTHETIC EXAMPLE 411 N-{[trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]methyl}- 3,3,3-trifluoro-N-(2,2,2-trifluoroethyl)propanamide The reactions in Synthetic Example 407 were carried out in substantially the same manners except that 3,3,3-trifluoropropionic acid was used instead of 2- cyanoacetic acid to give the title compound as a colorless solid (8.80 mg, yield 33%).

SYNTHETIC EXAMPLE 412 N-{[trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]methyl}-N- (cyanomethyl)-3,3,3-trifluoropropanamide The reactions in Synthetic Example 411 were carried out in substantially the same manners except that 2-({[trans(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin- 1-yl)cyclohexyl]methyl}amino)acetonitrile (Synthetic Example 259) was used instead of N-{[trans(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]methyl}- 2,2,2-trifluoroethanamine to give the title compound as a colorless solid (6.40 mg, yield 64%).

SYNTHETIC EXAMPLE 413 trans-N-(Cyclopropylmethyl)(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)-N- (2,2,2-trifluoroethyl)cyclohexanamine trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)-N-(2,2,2- trifluoroethyl)cyclohexanamine (5.00 mg, 0.0148 mmol) obtained in Synthetic Example 395 in methanol (1 mL) and acetic acid (0.1 mL) was mixed with cyclopropanecarbaldehyde (1.60 µL, 0.0222 mmol) and 2-picoline borane (2.30 mg, 0.0222 mmol) and stirred at room temperature for 1 day. After addition of 1 M aqueous sodium hydroxide, the reaction mixture was extracted with ethyl acetate. The orgnic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1/3 → 1/1 (v/v)) to give the title compound as a colorless solid (4.00 mg, yield 70%).

SYNTHETIC EXAMPLES 414 AND 415 The reactions in Synthetic Example 413 were carried out in substantially the same manners except that 2-({[trans(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin- 1-yl)cyclohexyl]methyl}amino)acetonitrile (Synthetic Example 259) or N-{[trans(7H- pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]methyl}-2,2,2- trifluoroethanamine (Synthetic Example 188) was used instead of trans(7H- pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)-N-(2,2,2-trifluoroethyl)cyclohexanamine to give the compounds of Synthetic Examples 414 and 415. The names, morphologies and yields of the compounds synthesized are shown in Table 43.

TABLE 43 Ex Compound Name Morphology Yield 2-({[trans(7H-pyrrolo[3,2-e][1,2,3 ]triazolo[1,5-c]pyrimidinyl)cycloh 414 colorless solid 73% exyl]methyl}(cyclopropylmethyl)amino) acetonitrile N-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 415 colorless solid 78% xyl]methyl}-N-(cyclopropylmethyl)-2,2 ,2-trifluoroethanamine SYNTHETIC EXAMPLE 416 [trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]methanesulfonic acid S-[trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]methyl ethanethioate (127 mg, 0.390 mmol) obtained in Synthetic Example 71 in methanol (4 mL) was mixed with ammonium molybdate tetrahydrate (145 mg, 0.117 mmol) and hydrogen peroxide solution (0.63 mL, 7.80 mmol) and stirred at room temperature for 1day. The reaction mixture was mixed with saturated aqueous sodium thiosulfate, concentrated under reduced pressure and purified by silica gel column chromatography (ethyl acetate / methanol = 4/1 → 1/1 (v/v)). The resulting solid was mixed with water and extracted with n-butanol. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the title compound as a pale yellow solid (39.8 mg, yield 28%).

SYNTHETIC EXAMPLE 417 1-[trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]-N- cyclopropylmethanesulfonamide [trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexyl]methanesulfonic acid (17.8 mg, 0.0530 mmol) in dichloromethane (1.5 mL) and N,N-dimethylformamide (1.8 mL) was stirred with thionyl chloride (0.00770 mL, 0.106 mmol) at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in dichloromethane (1.0 mL) and mixed with N,N-diisopropylethylamine (0.0923 mL, 0.530 mmol) and cyclopropylamine (0.0148 mL, 0.212 mmol) under cooling with ice and then stirred at room temperature for 1 day. After addition of water, the reaction mixture was extracted with ethyl acetate.

The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl hexane / acetate = 4/1 → 1/1 → 1/3 (v/v)) to give the title compound as a brown solid (1.50 mg, yield 7.5%).

SYNTHETIC EXAMPLES 418 TO 420 The reactions in Synthetic Example 417 were carried out in substantially the same manners except that dimethylamine hydrochloride, 2-aminoacetonitrile hydrochloride or 2,2,2-trifluoroethanamine hydrochloride was used instead of cyclopropylamine to give the compounds of Synthetic Examples 418 to 420. The names, morphologies and yields of the compounds synthesized are shown in Table 44.

TABLE 44 Ex Compound Name Morphology Yield 1-[trans(7H-pyrrolo[3,2-e][1,2,3]t 418 riazolo[1,5-c]pyrimidinyl)cyclohex colorless solid 15% yl]-N,N-dimethylmethanesulfonamide 1-[trans(7H-pyrrolo[3,2-e][1,2,3]t 419 riazolo[1,5-c]pyrimidinyl)cyclohex yellow solid 12% yl]-N-(cyanomethyl)methanesulfonamide 1-[trans(7H-pyrrolo[3,2-e][1,2,3]t riazolo[1,5-c]pyrimidinyl)cyclohex pale yellow 420 5.0% yl]-N-(2,2,2-trifluoroethyl)methanesu solid lfonamide SYNTHETIC EXAMPLE 421 1-(trans{[3-(2,2,2-Trifluoroethoxy)azetidinyl]methyl}cyclohexyl)-7H-pyrrolo[3,2- e][1,2,3]triazolo[1,5-c]pyrimidine tert-Butyl 3-(2,2,2-trifluoroethoxy)azetidinecarboxylate (350 mg, 1.37 mmol) obtained in Reference Synthetic Example 116 in ethyl acetate (1 mL) was mixed with 4 M hydrogen chloride - 1,4-dioxane solution (3 mL) under cooling with ice and then stirred at room temperature for 2 hours. The reaction mixture was concentrated to give a colorless oil (224 mg). The resulting colorless oil (64.0 mg) was dissolved in methanol (2 mL), tetrahydrofuran (1 mL) and acetic acid (100 µL) and stirred with trans- 4-(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexanecarbaldehyde (30.0 mg, 0.111 mmol) obtained in Synthetic Example 78 at room temperature for 1 hour.

The reaction mixture was mixed with 2-picoline borane (23.8 mg, 0.334 mmol) and stirred at room temperature for 14 hours. After addition of water, the reaction mixture was extracted with ethyl acetate. The aqueous layer was adjusted to pH 10 with 1 M aqueous sodium hydroxide, and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was washed with hexane / ethyl acetate (5/1 (v/v)) to give the title compound as a light purple solid (14.9 mg, yield 33%).

SYNTHETIC EXAMPLES 422 TO 424 The reactions in Synthetic Example 421 were carried out in substantially the same manners except that tert-butyl 3-hydroxymethylazetidinecarboxylate (Reference Synthetic Example 113), tert-butyl 3-(dimethylamino)azetidine carboxylate (Reference Synthetic Example 137) or tert-butyl 3- [ethyl(methyl)amino]azetidinecarboxylate (Reference Synthetic Example 138) was used instead of tert-butyl 3-(2,2,2-trifluoroethoxy)azetidinecarboxylate to give the compounds of Synthetic Examples 422 to 424. The names, morphologies and yields of the compounds synthesized are shown in Table 45.

TABLE 45 Ex Compound Name Morphology Yield 1-{[trans(7H-pyrrolo[3,2-e][1,2,3] 422 triazolo[1,5-c]pyrimidinyl)cyclohe colorless solid 21% xyl]methyl}methylazetidinol 1-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 423 colorless solid 25% xyl]methyl}-N,N-dimethylazetidinam 1-{[trans(7H-pyrrolo[3,2-e][1,2,3] triazolo[1,5-c]pyrimidinyl)cyclohe 424 colorless solid 34% xyl]methyl}-N-ethyl-N-methylazetidin- 3-amine SYNTHETIC EXAMPLE 425 1-{[trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]methyl} (trifluoromethyl)azetidinol The reactions in Synthetic Example 88 were carried out in substantially the same manners except that 3-(trifluoromethyl)azetidinol hydrochloride (Reference Synthetic Example 115) was used instead of thiomorpholine 1,1-dioxide to give the title compound as a colorless solid (11.9 mg, yield 27%).

SYNTHETIC EXAMPLE 426 1-{[trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]methyl}-N- (2,2,2-trifluoroethyl)azetidinecarboxamide 1-{[trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexyl]methyl}azetidinecarboxylic acid (40.0 mg, 0.113 mmol) obtained in Synthetic Example 278 and 2,2,2-trifluoroethanamine hydrochloride (19.9 mg, 0.147 mmol) in N,N-dimethylformamide (2 mL) were mixed with N,N-diisopropylethylamine (74.9 µL, 0.440 mmol) and (1-cyanoethoxyoxoethylidenaminooxy)dimethylamino- morpholino-carbenium hexafluorophosphate (62.8 mg, 0.147 mmol) and stirred at room temperature for 1 day. After addition of saturated aqueous sodium hydrogen carbonate, the reaction mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was washed with hexane / chloroform (3/1 (v/v)) to give the title compound as a pale yellow solid (5.40 mg, yield 11%).

SYNTHETIC EXAMPLE 427 N-{[trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexyl]methyl}methanesulfonamide [trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexyl]methanamine (20.0 mg, 0.0740 mmol) obtained in Synthetic Example 371 in dichloromethane (2 mL) was mixed with methanesulfonyl chloride (13.8 µL, 0.0814 mmol) under cooling with ice and then stirred at room temperature for 65 hours. After addition of water, the reaction mixture was extracted with ethyl acetate. The aqueous layer was washed with 1 M hydrochloric acid and saturated aqueous ammonium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was washed with chloroform / hexane (1/5 (v/v)) to give the title compound as a colorless solid (6.00 mg, yield 23%).

SYNTHETIC EXAMPLE 428 tert-Butyl 3-({[trans(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexyl]methyl}amino)(cyanomethyl)azetidinecarboxylate [trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexyl]methanamine (11.2 mg, 0.0414 mmol) obtained in Synthetic Example 371 and tert-butyl 3-(cyanomethylene)azetidinecarboxylate (10.4 mg, 0.0535 mmol) obtained in Reference Synthetic Example 139 in acetonitrile (2 mL) were mixed with 1,8-diazabicyclo[5.4.0]undecene (12.0 µL, 0.0535 mmol) and stirred at room temperature for 1 day. After addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (NH-silica gel manufactured by Fuji Silysia Chemical Ltd.; chloroform / methanol = 20/1 (v/v)) to give the title compound as a pale yellow solid (14.2 mg, yield 74%).

SYNTHETIC EXAMPLE 429 4-(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexanecarbaldehyde oxime [trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexylcarbaldehyde (60.0 mg, 0.223 mmol) obtained in Synthetic Example 78 in methanol (1 mL) and water (1 mL) was mixed with hydroxylamine hydrochloride (31.0 mg, 0.446 mmol) and sodium hydrogen carbonate (37.4 mg, 0.446 mmol) and then stirred at 50°C for 5 hours. The reaction mixture was filtered, and the resulting solid washed with water, water / methanol (10/1 (v/v)) and hexane to give the title compound as a colorless solid (44.6 mg, yield 70%).

SYNTHETIC EXAMPLE 430 trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexanecarbonitrile trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexanecarbaldehyde oxime (37.4 mg, 0.132 mmol) in dichloromethane (3 mL) was mixed with trifluoromethanesulfonic anhydride (24.0 µL, 0.145 mmol) and 1,8- diazabicyclo[5.4.0]undecene (43.0 µL, 0.289 mmol) and stirred at room temperature for 18 hours. After addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 3/2 (v/v)) and washed with hexane / ethyl acetate (5/1 (v/v)) to give the title compound as a colorless solid (20.7 mg, yield 59%).

SYNTHETIC EXAMPLE 431 2-{[trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexyl]methylene}malononitrile trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin 40 yl)cyclohexylcarbaldehyde (50.0 mg, 0.186 mmol) obtained in Synthetic Example 78 and malononitrile (24.5 mg, 0.371 mmol) were mixed with acetic acid (3 mL), piperidine (18.3 µL, 0.186 mmol) and dichloromethane (2 mL) under cooling with ice and stirred for 1 hours. The reaction mixture was mixed anhydrous sodium sulfate and then stirred room temperature for 17 hours. After addition of water, the reaction mixture was 45 extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / acetone = 2/1 → 3/2 (v/v)) to give the title compound as a colorless solid (36.3 mg, yield 62%).

SYNTHETIC EXAMPLE 432 2-{[trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexyl]methyl}malononitrile 2-{[trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexyl]methylene}malononitrile (25.8 mg, 0.0812 mmol) in tetrahydrofuran (3 mL) was mixed with diethyl 1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylate (30.8 mg, 0.122 mmol) and stirred at room temperature for 1 hours. After addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous ammonium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1/1 → 1/2 → 0/1 (v/v)) to give the title compound as a colorless solid (14.2 mg, yield 55%).

SYNTHETIC EXAMPLE 433 1-(4-Methylenecyclohexyl)-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine 1-[trans(Iodomethyl)cyclohexyl]-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine (15.0 mg, 0.0393 mmol) obtained in Synthetic Example 367 in tetrahydrofuran (1 mL) was mixed with (trifluoromethyl)trimethylsilane (7.60 µL, 0.0512 mmol) and tetrabutylammonium fluoride - tetrahydrofuran solution (1 M, 51.2 µL, 0.0512 mmol) under cooling with ice and then stirred at room temperature for 2 days. The reaction mixture was mixed with water, and the precipitate was collected by filtration. The resulting residue was purified by silica gel thin layer chromatography (ethyl acetate / hexane = 1/1 (v/v)) to give the title compound as a colorless solid (3.80 mg, yield 38%).

SYNTHETIC EXAMPLE 434 2-[4-(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexylidene]acetonitrile Diethyl (cyanomethyl)phosphonate (37.0 µL, 0.235 mmol) in tetrahydrofuran (1 mL) was mixed with sodium hydride (55 wt% dispersion in mineral oil, 10.0 mg, 0.235 mmol) under cooling with ice and then stirred for 30 minutes. The reaction mixture was mixed with 4-(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexanone (20.0 mg, 0.0783 mmol) obtained in Synthetic Example 82 and then stirred at room temperature for 30 minutes. After addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1/2 → 1/1 → 1/0 (v/v)) to give the title compound as a colorless solid (20.0 mg, yield 92%).

SYNTHETIC EXAMPLE 435 435a: 2-[cis(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin 40 yl)cyclohexyl]acetonitrile 435b: 2-[trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexyl]acetonitrile 2-[4-(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexylidene]acetonitrile (20.0 mg, 0.0720 mmol) in tetrahydrofuran (10 mL) were 45 stirred with 5% palladium-carbon (10 mg) at room temperature for 4 hours under a hydrogen atmosphere. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (hexane / ethyl acetate = 1/1 (v/v)) to give 2-[cis(7H-pyrrolo[3,2- e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]acetonitrile (Synthetic Example 435a; colorless solid, 1.30 mg, yield 6%) in a less polar fraction and 2-[trans(7H-pyrrolo[3,2- e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]acetonitrile (Synthetic Example 435b; colorless solid, 3.40 mg, yield 17%) in a more polar fraction.

SYNTHETIC EXAMPLES 436 AND 437 The reactions in Synthetic Example 434 were carried out in substantially the same manners except that ethyl 2-(diethoxyphosphoryl)acetate or diethyl (1- cyanoethyl)phosphonate was used instead of diethyl (cyanomethyl)phosphonate to give the compounds of Synthetic Examples 436 and 437. The names, morphologies and yields of the compounds synthesized are shown in Table 46.

TABLE 46 Ex Compound Name Morphology Yield ethyl 2-[4-(7H-pyrrolo[3,2-e][1,2,3]triazol 436 colorless solid 94% o[1,5-c]pyrimidinyl)cyclohexyliden e]acetate 2-[4-(7H-pyrrolo[3,2-e][1,2,3]triazol 437 o[1,5-c]pyrimidinyl)cyclohexyliden colorless solid 41% e]propanenitrile SYNTHETIC EXAMPLE 438 Ethyl 2-[4-(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]acetate The reactions in Synthetic Example 435 were carried out in substantially the same manners except that ethyl 2-[4-(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexylidene]acetate obtained in Synthetic Example 436 was used instead of 2- [4-(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexylidene]acetonitrile to give the title compound as a colorless solid (cis / trans mixture ; 29.0 mg, yield 51%).

SYNTHETIC EXAMPLE 439 439a: 2-[cis(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexyl]propanenitrile 439b: 2-[trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexyl]propanenitrile The reactions in Synthetic Example 435 were carried out in substantially the same manners except that 2-[4-(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexylidene]propanenitrile obtained in Synthetic Example 437 was used instead of 2-[4-(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexylidene]acetonitrile to give 2-[cis(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexyl]propanenitrile (Synthetic Example 439a; colorless solid, 0.750 mg, yield 7%) in a less polar fraction and 2-[trans(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5- c]pyrimidinyl)cyclohexyl]propanenitrile (Synthetic Example 439b; colorless solid, 2.00 mg, yield 19%) in a more polar fraction.

SYNTHETIC EXAMPLE 440 (E)[trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexyl]acrylonitrile The reactions in Synthetic Example 434 were carried out in substantially the same manners except that trans(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexanecarbaldehyde (30.0 mg, 0.111 mmol) obtained in Synthetic Example 78 was used instead of 4-(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexanone to give the title compound as a colorless solid (3.60 mg, yield 7%).

SYNTHETIC EXAMPLE 441 3-[trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]propanenitrile The reactions in Synthetic Example 438 were carried out in substantially the same manners except that (E)[trans(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5- c]pyrimidinyl)cyclohexyl]acrylonitrile obtained in Synthetic Example 440 was used instead of ethyl 2-[4-(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin yl)cyclohexylidene]acetate to give the title compound as a colorless solid (7.30 mg, yield 72%).

SYNTHETIC EXAMPLE 442 442a: 2-[cis(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]-N-2,2,2- trifluoroethylacetamide 442b: 2-[trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]-N- 2,2,2-trifluoroethylacetamide Ethyl 2-[4-(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]acetate (10.0 mg, 0.0305 mmol) obtained in Synthetic Example 438 in tetrahydrofuran (1 mL) was mixed with ethanol (0.5 mL), water (0.25 mL) and 1 M aqueous lithium hydroxide (60 µL, 0.0611 mmol) and stirred at room temperature for 4 hours. The reaction mixture was mixed with 1 M hydrochloric acid and concentrated under reduced pressure.

The residue was dissolved in N,N-dimethylformamide (2 mL) and stirred with O-(7- azabenzotriazolyl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (23.2 mg, 0.0610 mmol), N,N-diisopropylethylamine (21.0 µL, 0.122 mmol) and 2,2,2- trifluoroethanamine hydrochloride (8.30 mg, 0.0610 mmol) at room temperature for 13 hours. After addition of saturated aqueous ammonium chloride, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (ethyl acetate) to give 2-[cis(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5- c]pyrimidinyl)cyclohexyl]-N-(2,2,2-trifluoroethyl)acetamide (Synthetic Example 442a; colorless solid, 5.80 mg, yield 50%) in a less polar fraction and 2-[trans(7H- Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]-N-(2,2,2- trifluoroethyl)acetamide (Synthetic Example 442b; colorless solid, 3.10 mg, yield 27%) in a more polar fraction.

SYNTHETIC EXAMPLE 443 443a: 2-[cis(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]-N- (cyanomethyl)acetamide 443b: 2-[trans(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]-N- 40 (cyanomethyl)acetamide The reactions in Synthetic Example 442 were carried out in substantially the same manners except that 2-aminoacetonitrile hydrochloride was used instead of 2,2,2- trifluoroethanamine hydrochloride to give 2-[cis(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5- c]pyrimidinyl)cyclohexyl]-N-(cyanomethyl)acetamide (Synthetic Example 443a; pale 45 brown solid, 7.00 mg, yield 47%) in a less polar fraction and 2-[trans(7H-pyrrolo[3,2- e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexyl]-N-(cyanomethyl)acetamide (Synthetic Example 443b; pale brown solid, 3.80 mg, yield 25%) in a more polar fraction.

SYNTHETIC EXAMPLE 444 6-(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)spiro[2.5]octanecarbonitrile Trimethylsulfonium iodide (59.0 µL, 0.269 mmol) in dimethyl sulfoxide (1 mL) was stirred with sodium hydride (55 wt% dispersion in mineral oil, 12.0 mg, 0.269 mmol) at room temperature for 30 minutes. The reaction mixture was mixed with 2-[4-(7H- pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)cyclohexylidene]acetonitrile (15.0 mg, 0.0539 mmol) obtained in Synthetic Example 434 and then stirred at room temperature for 15 hours. After addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1/1 (v/v)) to give the title compound as a colorless solid (5.80 mg, yield 37%).

SYNTHETIC EXAMPLE 445 3-(7H-Pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidinyl)adamantanol (3-Hydroxyadamantanyl)(7H-pyrrolo[2,3-d]pyrimidinyl)methanone (22.5 mg, 0.0757 mmol) obtained in Reference Synthetic Example 141 in methanol (1.5 mL) was mixed with hydrazine hydrate (0.141 mL, 2,27 mmol) and then stirred at 80°C for 2 hours. The reaction mixture was mixed with hydrazine hydrate (0.118 mL, 1.89 mmol) and acetic acid (1 drop) and stirred at 80°C for 2 hours. The reaction mixture was mixed with ethyl acetate, washed with water and saturated sodium chloride. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was dissolved in chloroform (1.5 mL) and mixed with manganese(IV) oxide (32.9 mg, 0.379 mmol). The reaction mixture was stirred at 70°C for 6 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (ethyl acetate) and further by silica gel thin layer chromatography (NH-PLC05 plate manufactured by Fuji Silysia Chemical Ltd.: ethyl acetate / hexane = 15/1) to give the title compound as a colorless solid (3.30 mg, yield 14%).

The structural formulae of the compounds obtained the Reference Synthetic a a a Examples and Synthetic Examples are shown below in Tables 47 to 80. The physical property data on the compounds obtained the Reference Synthetic Examples and Synthetic Examples are shown below in Tables 81 to 151.

TABLE 47 R f S tr u c tur e R f St r uc t ur e R f St ru ct ur e I HO 1 2 3 TIPS TIPS r a c e m a t e 4 5 6 TIPS H SEM 7 N 8 9 SEM N r a c e m a t e SEM 1 0 1 1 12 1 3 1 4 15 d i a s t e r e o m i x t u r e d i a s t e r e o m i x t u r e Ph O Ph O N OH 1 6 17 r a c e m a t e r a c e m a t e H N N O Ph O N O Ph 2 1 8 1 9 20 racemate racemate SEM N d i a s t e r e o m i x t u r e OTBDPS OTBDPS 2 1 N 2 2 N 23 OTBDPS TABLE 48 R f Str u c tur e R f Str uc tu r e R f S tr u ct ur e O N O O N O N N O 2 5 26 2 7 O O N d i a s t e r e o m i x t u r e d i a s t e r e o m i x t u r e N d i a s t e r e o m i x t u r e O N O N N O HO N O 2 8 29 3 0 r a c e m a t e racem ate N r a c e m a t e O N O N N O HO N 3 1 32 3 3 O O N racem ate r a c e m a t e r a c e m a t e 3 4 35 3 6 r a c e m a t e r a c e m a t e O N N O 3 7 38 3 9 NH O F N H C l 4 0 41 O 4 2 N O H 4 3 44 4 5 TABLE 49 R f Str uc tu re R f Str u c tur e R f Str u c tur e 46 4 7 48 O OH 49 O 5 0 51 N 52 N 5 3 54 55 O 5 6 N 57 d i a s t e r e o m i x t u r e 58 5 9 60 61 6 2 63 d i a s t e r e o m i x t u r e 64 6 5 66 OTBDPS OTBDPS 67 6 8 O 69 TABLE 50 R f Str u c tur e R f S t r uc t ur e R f S t ruc tu r e OTBDPS OTBS 70 7 1 O 7 2 cis/trans mixture cis/trans mixture cis/trans mixture OTBS OTBS 73 7 4 7 5 H N N cis/trans mixture cis/trans mixture cis/trans mixture O H N 76 7 7 7 8 N racemate H C l 79 8 0 8 1 racemate H N F F N O 82 8 3 8 4 N racemate OTBS OTBS 85 8 6 8 7 TABLE 51 R f Stru c tur e R f Str u ct ur e R f Str u ct ur e OTBS OH OTBS 8 8 8 9 9 0 O OTBS OTBS 9 1 9 2 9 3 N N N O H N 9 4 9 5 9 6 N N racemate H SEM SEM 9 7 9 8 N 9 9 racemate N racemate F F F F F OH F OH F OH NH NH 1 00 1 01 2 10 2 2 Cl racemate racemate racemate F 1 03 1 04 racemate TABLE 52 R f Str uc tu r e R f S t ruc t ur e R f St r uc t ure 5 10 6 2 1 07 F N O 8 10 9 1 10 O 11 1 11 2 1 13 OH F 11 4 11 5 1 16 H N H N 11 7 11 8 2 1 19 racemate racemate HO HO 2 H N H N O 12 0 12 1 2 1 22 2 racemate racema te racemate 12 3 12 4 1 25 N EtO C EtO C diastereomixture diastereomixture 1 28 O N H N OH 12 6 12 7 diastereomixture racemate 12 8 H 12 9 1 30 O N OH OTBS 13 1 13 2 1 33 cis/trans mixture TABLE 53 R f Str uc tu r e R f S t ruc t ur e R f St r uc t ure OTBS OTBS OTBS 1 35 N 13 5 N 13 4 cis/trans mixture 13 6 13 7 13 8 13 9 14 0 14 1 TABLE 54 E x Str u c tur e Ex Str uc tu r e E x S tru ct ur e 1 2 3 r a c e m a t e 4 5 6 r a c e m a t e HN HN 7 8 9 H N N d i a s t e r e o m i x t u r e TABLE 55 Ex Str uc tu r e Ex St ruc t ur e Ex Str uc tu r e 1 1 12 N 13 d i a s t e r e o m i x t u r e H racemate d i a s t e r e o m i x t u r e 1 4 15 16 racemate racemate racemate 1 7 18 N 19 racemate racemate racemate N O O 2 0 N 21 22 N racemate H racemate racemate 2 3 24 25 N racemate 2 6 27 28 TABLE 56 Ex Stru c tur e E x Str u ct ur e E x Str u ct ur e O O O NH NH N N N 2 9 3 0 3 1 N N N N N N N N N N N N N N N H H H N N N 3 2 3 3 3 4 3 5 3 6 3 7 N N N 3 8 3 9 F 4 0 4 1 4 2 4 3 4 4 4 5 N 4 6 N N N TABLE 57 Ex Str uc tu r e Ex St ruc t ur e Ex Str uc tu r e F S S 4 7 48 49 N N N 0 51 52 3 54 55 56 a 56 b 57 cis/trans cis/trans N unknown N unknown N less polar fraction more polar fraction 8 59 60 6 1 62 63 TABLE 58 Ex Str uc tu re E x Str u c tur e E x Str u c tur e 64 6 5 66 d i a s t e r e o m i x t u r e 67 6 8 69 70 7 1 72 F Br Cl N N N 73 7 4 75 N N N N N N N N N H H H 76 7 7 78 F OH 79 8 0 81 TABLE 59 Ex Str uc tu re E x Str u c tur e E x Str u c tur e O OH O 82 8 3 84 N N N N N N H H H 85 8 6 87 88 8 9 90 91 9 2 93 94 9 5 96 97 9 8 99 TABLE 60 Ex Str uc tu re E x Str u c tur e E x Str u c tur e 1 00 1 01 1 02 N N N 1 03 1 04 1 05 1 06 1 07 1 08 N F H 1 09 1 10 1 11 racemate 1 12 N 1 13 1 14 Cl F 1 15 1 16 1 17 N N N TABLE 61 Ex Str uc tu re E x Str u c tur e E x Str u c tur e 1 18 1 19 1 20 1 21 1 22 1 23 N cis/trans cis/trans cis/trans mixture N mixture N mixture 1 24 1 25 1 26 N cis/trans mixture cis/trans cis/trans N H mixture mixture 1 27 1 28 1 29 cis/trans mixture N N cis/trans cis/trans H N mixture N mixture 1 30 1 31 1 32 cis/trans cis/trans cis/trans mixture mixture H mixture 1 34 1 34 1 33 N N cis/trans N mixture TABLE 62 Ex Str uc tu re E x Str u c tur e E x Str u c tur e 1 35 1 35 1 36 a b a N H H 1 36 1 37 1 37 b a b 1 38 1 38 1 39 a b a N N H H OH 1 39 N N 1 40 1 41 1 42 1 43 1 44 N F N N 1 45 1 46 1 47 TABLE 63 Ex Str uc tu re E x Str u c tur e E x Str u c tur e Br Cl N N N N N N 1 48 1 49 1 50 N N N H H H N N N 1 51 1 52 1 53 N N N N N N F Cl 1 54 1 55 1 56 1 57 1 58 1 59 1 60 1 61 1 62 1 63 1 64 1 65 TABLE 64 Ex Str uc tu re E x Str u c tur e E x Str u c tur e 1 66 1 67 1 68 N O O 1 69 N 1 70 1 71 1 72 1 73 1 74 racemate 1 75 1 76 1 77 1 78 1 79 1 80 1 81 1 82 1 83 TABLE 65 Ex Str uc tu r e Ex St ruc t ur e Ex St r uc tu r e OH OH 18 4 18 5 1 86 racemate H H N 18 7 18 8 1 89 19 0 19 1 1 92 H C l 1 94 1 94 19 3 H N N 19 5 1 95 1 96 a b a N N N racemate N N N N N N F F Cl 19 6 1 97 1 97 b a b racemate TABLE 66 Ex Str uc tu re E x Str u c tur e E x Str u c tur e Cl N 1 98 1 99 2 00 b b b N racemate N racemate 2 01 2 02 2 03 b b b racemate 2 04 2 05 N 2 06 cis/trans mixture N 2 07 2 08 2 09 N OH 2 10 2 11 N 2 12 N racemate racemate TABLE 67 Ex Str uc tu r e E x S t ruc t ur e E x St r uc t ure N Cl 21 3 21 4 2 15 21 6 21 7 2 18 21 9 22 0 2 21 22 2 22 3 2 24 22 5 22 6 2 27 O Cl 22 8 22 9 2 30 TABLE 68 Ex Str uc tu r e E x S t ruc t ur e E x St r uc t ure N Cl 23 1 23 2 23 3 23 4 23 5 23 6 H N H 23 7 23 8 23 9 N N N 24 0 24 1 24 2 24 3 24 4 24 5 racemate 24 6 24 7 24 8 TABLE 69 Ex Str uc tu r e E x S t ruc t ur e E x St r uc t ure 24 9 25 0 2 51 2 25 3 2 54 racemate 5 25 6 2 57 N N H 8 25 9 2 60 N Cl 26 1 26 2 2 63 OH OH 26 4 26 5 2 66 N N N N N N H H H TABLE 70 Ex Str uc tu r e E x S t ruc t ur e E x St r uc t ure N Br 26 7 26 8 2 69 27 0 N 27 1 2 72 H H N 27 3 27 4 2 75 N N N N N N 27 6 27 7 2 78 27 9 28 0 2 81 racemate N 28 2 28 3 2 84 TABLE 71 Ex Str uc tu r e E x S t ruc t ur e E x St r uc t ure 28 5 N 28 6 2 87 N N N N H H 28 8 28 9 2 90 racemate N N N H H H 29 1 29 2 2 93 N N N diastereomixture N N N 29 4 29 5 2 96 OH OH 29 7 29 8 2 99 0 30 1 N 3 02 TABLE 72 Ex Str uc tu r e E x S t ruc t ur e E x St r uc t ure 3 30 4 3 05 6 30 7 N 3 08 9 31 0 3 11 Cl N H N N 31 2 N 31 3 3 14 31 5 31 6 3 17 31 8 31 9 3 20 N N N TABLE 73 Ex Str uc tu r e E x S t ruc t ur e E x St r uc t ure 32 1 32 2 N 3 23 32 4 32 5 3 26 N N N N N N 32 7 32 8 N 3 29 H N N 33 0 33 1 3 32 33 3 33 4 3 35 N N N 33 6 33 7 3 38 TABLE 74 Ex Str uc tu r e E x S t ruc t ur e E x St r uc t ure 33 9 34 0 3 41 H OH 34 2 34 3 3 44 racemate O HO F N 34 5 34 6 3 47 racemate N N racemate 34 8 34 9 N 3 50 N N OH 1 35 2 3 53 racemate N N N N N N H H H 4 N 35 5 N 3 56 TABLE 75 Ex Str uc tu r e E x S t ruc t ur e E x St r uc t ure OH O 7 N 35 8 3 59 N N N OH O 36 0 36 1 3 62 36 3 36 4 3 65 36 6 36 7 3 68 N OH 36 9 37 0 3 71 F Cl 37 2 37 3 3 74 TABLE 76 Ex Str uc tu r e E x S t ruc t ur e E x St r uc t ure 37 5 37 6 3 77 HO HO 37 8 37 9 3 80 N N cis/trans cis/trans cis/trans mixture mixture mix ture N N N 38 1 3 81 3 82 a b a N F F 38 2 3 83 3 83 b a b H N N F F F F HO 38 4 3 84 3 85 a b b racema te N N N HO HO 38 6 3 87 3 88 b b b N N N racemate racemate racemate TABLE 77 Ex Str uc tu r e E x S t ruc t ur e E x St r uc t ure HO H 38 9 3 90 3 91 b b b racemate diastereomixture N N H N 39 2 3 93 3 94 b b b N N N 39 5 3 96 3 97 b b b 39 8 3 99 4 00 F b b b 40 1 40 2 4 03 40 4 40 5 4 06 TABLE 78 Ex Str uc tu r e E x S t ruc t ur e E x St r uc t ure 40 7 40 8 4 09 41 0 41 1 4 12 F 41 3 41 4 4 15 41 6 N 41 7 4 18 41 9 42 0 4 21 42 2 42 3 4 24 TABLE 79 Ex Str uc tu r e E x S t ruc t ur e E x St r uc t ure 42 5 42 6 4 27 N OH 42 8 42 9 4 30 mixture N N N N N N 43 1 43 2 4 33 H H H N 4 35 N 4 35 N 43 4 racemate N N N N N N N N N N N N H H H 43 6 43 7 4 38 racemate racemate cis/trans mixture N N N 43 9 4 39 4 40 N N N TABLE 80 Ex Str uc tu r e E x S t ruc t ur e E x St r uc t ure 4 42 4 42 44 1 44 3 4 43 4 44 diastereomixture N N H 44 5 TABLE 81 R f D ata H -N MR ( DM S O- d ) δ: 6.63 (d, J = 2. 6 H z, 1H ), 7. 67 ( t , J = 2.6 Hz , 1H ), 8. 44 ( s, 1H ). 1 LC /M S: con dit io n 1, ret enti on ti m e = 2. 61 mi n LC /M S( ES I ) m /z; 246 [M +H ] LC /M S( ES I ) m /z; 244 [ M-H ] H -N MR (C D Cl ) δ: 1. 11 (d, J = 7.2 H z, 18H ), 1.79- 1.89 ( m, 3H ), 6.46 (d, J = 3. 3 H z, 1H ), 7. 31 (d, J = 3.6 Hz, 1H ), 8.4 7 (s , 1H) .

LC /M S: con dit io n 1, ret enti on ti m e = 5. 97 mi n LC /M S( ES I ) m /z; 402 [M +H ] LC /M S: con dit io n 1, ret enti on ti m e = 4. 91 mi n LC /M S( ES I ) m /z; 388 [M +H ] LC /M S: con dit io n 1, ret enti on ti m e = 4. 05 mi n 4 + + LC /M S( ES I ) m /z; 230 [M -T I PS ] H -N MR (C D OD ) δ: 1. 46 ( dd, J = 18.8、 9.5 Hz, 4H ), 1. 70-2. 00 (m , 6H ), 3. 90-4. 00 (m , 1H) , 7.08 (d, J = 3.6 H z, 1H ), 7. 63 ( d, J = 3.6 H z, 1H ), 8. 88 ( s, 1H ).

LC /M S: con dit io n 1, ret enti on ti m e = 4. 02 mi n LC /M S( ES I ) m /z; 230 [M +H ] LC /M S( ES I ) m /z; 228 [ M-H ] H -N MR (C DC l ) δ: - 0.06 ( s, 9H) , 0. 81-0. 97 ( m, 2H) , 1. 19-1. 60 (m , 5H ), 1. 69-2. 07 (m , 5H) , 3. 45-3. 58 ( m, 2H ) , 3.86- 4.03 ( m, 1H ), 5.68 (s, 6 2H ), 7. 18-7. 26 ( m, 1H ), 7. 51 ( d, J = 3. 6 Hz, 1H ) , 9.01 (s, 1H ).

LC /M S: con dit io n 1, ret enti on ti m e = 5. 59 mi n LC /M S( ES I ) m /z; 360 [M +H ] LC /M S: con dit io n 1, ret enti on ti m e = 3. 39 mi n LC /M S( ES I ) m /z; 361 [M +H ] LC /M S: con dit io n 1, ret enti on ti m e = 4. 54 mi n 8 + + LC /M S( ES I ) m /z; 371 [M +1] H -N MR (C DC l ) δ: 2.34 ( s, 3H ) , 3. 30 (s, 3H) , 3. 53 (br s, 3H ) , 7. 12-7. 22 (m , 3H ), 7. 27-7. 39 ( m, 1H ).

LC /M S: con dit io n 1, ret enti on ti m e = 2. 94 mi n LC /M S( ES I ) m /z; 180 [M +H ] H -N MR (C DC l ) δ: 2. 46 (s, 3H ), 7. 02-7. 10 (m , 1H ), 7.21- 7.39 (m , 2H ), 7.40- 7.48 (m , 1H) , 7. 50-7. 58 (m , 2H ), 9. 01 (s, 1H) , 9. 49 (br s, 1H ).

LC /M S: con dit io n 1, ret enti on ti m e = 3. 59 mi n LC /M S( ES I ) m /z; 238 [M +H ] LC /M S( ES I ) m /z; 236 [ M-H ] H -N MR ( CD Cl ) δ: 1. 15-1. 58 (m, 5H ) , 1.61- 1.90 (m , 5H) , 2.58- 2.78 (m , 1H ), 3. 17 ( s, 3H) , 3.6 9 (s , 3H) .

LC /M S: con dit io n 1, ret enti on ti m e = 3. 47 mi n LC /M S( ES I ) m /z; 172 [M +H ] H -N MR ( CD Cl ) δ: 1. 19-1. 60 (m, 5H ) , 1.68- 2.10 (m , 5H) , 3.85- 4.07 (m , 1H ), 7.19 -7.2 5 ( m, 1H) , 7. 45-7. 58 (m , 1H ), 9.00 ( s, 1H ), 9.43 ( br s, 1H ).

LC /M S: con dit io n 1, ret enti on ti m e = 4. 05 mi n LC /M S( ES I ) m /z; 230 [M +H ] LC /M S( ES I ) m /z; 228 [ M-H ] TABLE 82 R f D ata H -N MR ( CD C l ) δ: 0.91( s, 1. 5H ), 0. 94 ( s, 1. 5H) , 1.2 1-1. 91 ( m, 8H ) , 2. 00-2. 19 (m , 1H ), 2. 80-2. 94 ( m, 1H ), 3. 17 ( s, 3H ), 3. 68 ( s, 3H ).

LC /M S: con dit io n 1, ret enti on ti m e = 3. 84 mi n LC /M S( ES I ) m/ z; 186 [M+ H ] H -N MR ( CD Cl ) δ: 0. 77-0. 86 (m, 3H ) , 1.20- 2.00 (m , 8H) , 2.31- 2.50 (m , 1H ) , 4.10- 4.20 (m , 1H ) , 7.17 -7.22 ( m, 1H ) , 7. 43-7. 52 ( m, 1H) , 8. 98 ( s, 1H) , 9.18 (br s , 1H) .

LC /M S: con dit io n 1, ret enti on ti m e = 4. 22 mi n LC /M S( ES I ) m /z; 244 [M +H ] LC /M S( ES I ) m /z; 242 [ M-H ] LC /M S: con dit io n 2, ret enti on ti m e = 4. 17 mi n LC /M S( ES I ) m /z; 376 [M +H ] H -N MR ( CD C l ) δ: 1. 10-1. 90 (m, 5H ) , 2.73- 3.20 (m , 2H) , 3.5 0 ( t, J = 6. 0 H z, 2H ), 3. 65-4. 15 ( m, 2H ), 5. 13 ( br s, 2H ), 7. 22-7. 41 ( m, 5H ).

LC /M S: con dit io n 1, ret enti on ti m e = 3. 89 mi n LC /M S( ES I ) m /z; 307 [M +H ] LC /M S: con dit io n 1, ret enti on ti m e = 5. 34 mi n LC /M S( ES I ) m /z; 495 [M +H ] LC /M S: con dit io n 2, ret enti on ti m e = 3. 77 mi n LC /M S( ES I ) m /z; 496 [M +H ] LC /M S: con dit io n 1, ret enti on ti m e = 4. 87 mi n LC /M S( ES I ) m /z; 506 [M +H ] H -N MR ( CD Cl ) δ: 0. 93-1. 13 (m, 2H ) , 1.20- 1.32 (m , 1H) , 1.44- 1.65 (m , 2H ) , 1.7 8-1.9 3 ( m, 4H ), 2. 56-2. 74 (m , 1H ), 3.18 ( s, 3H ), 3.48 ( t, J 21 = 6.0 H z, 2H) , 3.6 9 ( s, 3H ).

LC /M S: con dit io n 1, ret enti on ti m e = 1. 22 mi n LC /M S( ES I ) m /z; 202 [M +H ] H -N MR (C DC l ) δ: 1. 05 (s, 9H ), 1. 40-1. 68 (m , 5H ), 1.72- 1.95 (m , 4H ), 2. 51-2. 73 (m, 1H) , 3.18 ( s, 3H ), 3. 47 ( d, J = 6. 3 H z, 2H ), 3.69 22 (s , 3H) , 7.28- 7.48 (m , 6H ), 7. 53-7. 72 ( m, 4H ).

LC /M S: con dit io n 1, ret enti on ti m e = 5. 67 mi n LC /M S( ES I ) m /z; 440 [M +H ] H -N MR (C DC l ) δ: 1. 07 (s, 9H ), 1. 42-1. 68 (m , 5H ), 1.87- 2.00 (m , 3H ), 2. 01-2. 13 (m , 1H) , 3.53 (d, J = 6. 0 H z, 2H) , 3.81- 4.00 (m , 1H ) , 7. 20-7. 27 (m , 1H ), 7.30- 7.43 ( m, 6H) , 7. 45-7. 53 (m , 1H ), 7. 59-7.73 (m , 4H ), 9. 01 ( d, J = 4. 5 H z, 1H ), 9. 07 (br s, 1H ).

LC /M S: con dit io n 1, ret enti on ti m e = 5. 94 mi n LC /M S( ES I ) m /z; 498 [M +H ] H -N MR (C DC l ) δ: 1. 09 (s, 9H ), 1. 17-1. 37 (m , 2H ), 1.68- 1.82 (m , 1H ), 1. 83-2. 21 (m , 6H) , 3.07- 3.22 (m, 1H ), 3. 58 ( d, J = 6.3 Hz, 2H ), 6. 75-6. 85 (m , 1H ), 7.25- 7.32 ( m, 1H) , 7. 33-7. 50 (m , 6H ), 7. 62-7.78 24 (m , 4H ), 9. 01 ( br s, 1H ), 9. 21 ( s, 1H ).

LC /M S: con dit io n 1, ret enti on ti m e = 5. 67 mi n LC /M S( ES I ) m /z; 510 [M +H ] LC /M S( ES I ) m /z; 508 [ M-H ] TABLE 83 Rf D ata H -N MR (C DC l ) δ: 0. 90-0. 98 (m , 3H ), 1.45 (s, 9H ), 1. 30-1. 90 (m , 4H ), 2.0 5-2. 30 (m , 1H ), 2.50 -2.8 5 (m , 1H ) , 3. 30-3. 50 (m , 1H ) , 3. 50-4. 20 ( m, 4H ).

H -N MR ( CD C l ) δ: 0. 87-1. 01 (m , 3H ), 1.41- 1.47 (m , 9H) , 1.54- 1.79 ( m, 4H ), 2.80 (s , 2H) , 2.89 ( q, J = 6.3 H z, 1H ), 3. 15-3. 22 ( m, 3H ) , 26 3. 56 ( br s, 1H ), 3. 68-3. 73 ( m, 3H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 97 m in + t + LC /M S (E SI ) m /z; 231 [M - B u] LC /M S : condit i on 1, re tent ion ti m e = 4. 12 m in 27 LC /M S (E SI ) m /z; 345 [M +H ] LC /M S (E SI ) m /z; 343 [ M- H] H -N MR (C DC l ) δ: 1. 46 (s, 9H ), 1. 48-1. 56 (m , 1H ), 1. 58-1. 76 (m , 2H ), 1. 88-1. 97 ( m, 1H ), 2. 63-2 .95 (m , 3H) , 3.19 (s , 3H) , 3.73 (s, 28 3H ), 4. 03-4. 22 ( m, 2H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 60 m in + t + LC /M S (E SI ) m /z; 273 [M - B u] LC /M S : condit i on 1, re tent ion ti m e = 3. 87 m in + t + 29 LC /M S (E SI ) m /z; 275 [M - B u] LC /M S (E SI ) m /z; 329 [ M- H] LC /M S : condit i on 1, re tent ion ti m e = 2. 88 m in LC /M S (E SI ) m /z; 222 [M +H ] LC /M S : condit i on 1, re tent ion ti m e = 3. 52 m in 31 LC /M S (E SI ) m /z; 235 [M +H ] LC /M S (E SI ) m /z; 233 [ M- H] H -N MR ( CD C l ) δ: 1. 65-1. 75 (m , 2H ), 1.80- 1.87 (m , 1H) , 2.16- 2.23 ( m, 1H ), 2.91- 3.02 (m , 1H ), 3. 22 (br s, 1H) , 4. 08-4.1 9 ( m, 2H ), 4.38 ( br s, 1H ), 5. 10-5. 18 (m , 2H) , 7. 21 (d d, J = 3.6, 2. 0 Hz, 1H) , 7. 28-7. 39 (m , 5H ), 7.51 (dd , J = 4. 0, 2. 3 H z, 1H ), 8.95 ( br s, 1H ) , 9. 42 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 90 m in LC /M S (E SI ) m /z; 365 [M +H ] LC /M S (E SI ) m /z; 363 [ M- H] H -N MR ( CD C l ) δ: 1. 35-1. 80 (m , 3H ), 2.00- 2.15 (m , 1H) , 2.40- 2.59 ( m, 1H ), 2. 93 ( ddd, J = 13. 0, 10. 7, 3. 0 H z, 1H) , 2.95- 3.26 (m , 1H ) , 3. 92-4. 02 ( m, 1H ) , 4.02- 4.35 (m , 1H ), 5. 11 (d, J = 12. 4 H z, 1H ), 5.16 33 ( d, J = 12. 4 H z, 1H ), 7. 27-7. 34 (m , 5H) .

LC /M S : condit i on 1, re tent ion ti m e = 3. 52 m in LC /M S (E SI ) m /z; 264 [M +H ] LC /M S (E SI ) m /z; 262 [ M- H] H -N MR ( CD C l ) δ: 1. 40-1. 81 (m , 3H ), 1.87- 2.00 (m , 1H) , 2.68- 3.05 ( m, 3H) , 3.16 ( s, 3H) , 3. 59-3. 70 (m , 3H) , 4.05- 4.34 ( m, 2H ), 5.11 (d, 34 J = 12.7 H z, 1H) , 5.16 (d, J = 12. 7 H z, 1H ), 7. 28-7. 39 ( m, 5H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 70 m in LC /M S (E SI ) m /z; 307 [M +H ] LC /M S : condit i on 1, re tent ion ti m e = 0. 77 m in + + LC /M S (E SI ) m /z; 321 [M +H ] TABLE 84 Rf D ata H -N MR ( CD C l ) δ: 1. 16-1. 40 (m , 3H ), 1.61- 1.82 (m , 1H) , 1.85- 2.09 ( m, 4H ), 2 .10- 2.26 (m , 2H) , 3. 09-3. 25 ( m, 1H ), 3.58 (t , J = 6.0 H z, 2H ), 6. 74-6. 85 (m , 1H ), 7. 20-7. 32 (m , 1H ), 9. 04 (br s, 1H) , 9. 22 (s , 36 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 2. 99 m in LC /M S (E SI ) m /z; 272 [M +H ] LC /M S (E SI ) m /z; 270 [ M- H] H -N MR ( CD C l ) δ: 0. 93-1. 13 (m , 2H ), 1.20- 1.32 (m , 1H) , 1.44- 1.65 ( m, 2H ), 1. 78-1. 93 ( m, 4H ), 2.56- 2.74 (m, 1H ) , 3.18 (s, 3H ), 3 .48 (t , 37 J = 6.0 Hz, 2 H) , 3.69 (s , 3H) .

LC /M S : condit i on 1, re tent ion ti m e = 1. 22 m in LC /M S (E SI ) m /z; 202 [M +H ] H -N MR (C DC l ) δ: 1. 46 (s, 9H ), 1. 60-1. 81 (m , 4H ), 2. 65-2. 90 (m , 3H ), 3. 18 ( s, 3H ), 3. 71 ( s, 3H ), 4. 00-4. 30 ( m, 2H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 66 m in LC /M S (E SI ) m /z; 273 [M +H ] H -N MR ( CD C l ) δ: 1. 40-1. 53 (m , 9H ), 1.55- 1.82 (m , 2H) , 1.87- 2.10 ( m, 2H ) , 2.80- 3.10 ( m, 2H) , 4. 00-4. 37 ( m, 3H) , 7. 15-7. 30 (m , 1H ), 7. 46-7. 59 ( m, 1H ), 8. 90-9. 08 ( m, 1H ), 9. 53 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 87 m in LC /M S (E SI ) m /z; 331 [M +H ] LC /M S (E SI ) m /z; 329 [ M- H] H -N MR (D MS O -d ) δ: 1. 63-1. 89 (m , 4H ), 2.82- 3.04 ( m, 3H ), 3. 10 (s , 3H ), 3. 18-3. 31 ( m, 2H ), 3. 69 ( s, 3H ), 8. 73 ( br s, 1H ), 9. 07 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 0. 50 m in LC /M S (E SI ) m /z; 173 [M +H ] H -N MR ( CD C l ) δ: 1. 65-1. 92 (m , 4H ), 2.38- 2.51 (m , 2H) , 2.57- 2.72 ( m, 1H ), 2. 92-3. 06 ( m, 4H ), 3.18 (s, 3H ), 3. 70 ( s, 3H ).

LC /M S : condit i on 1, re tent ion ti m e = 0. 74 m in LC /M S (E SI ) m /z; 255 [M +H ] H -N MR ( CD C l ) δ: 1. 78-2. 05 (m , 4H ), 2.56- 2.68 (m , 2H) , 2.87- 3.12 ( m, 4H) , 3. 87-4. 00 (m , 1H ) , 7. 22-7. 25 (m , 1H ), 7.26 ( s, 1H ) , 42 7. 50-7. 56 ( m, 1H ), 8. 99 ( s, 1H ), 9. 74 ( br s, 1H) .

LC /M S : condit i on 1, re tent ion ti m e = 2. 75 m in LC /M S (E SI ) m /z; 313 [M +H ] H -N MR (C DC l ) δ: 1. 64-1. 82 (m , 4H ), 2.76- 2.95 (m , 3H ), 3.18 (s , 3H ), 3. 71 ( s, 3H ), 4. 12-4. 30 ( m, 2H ) , 5 ,13 (s, 2H ) , 7.25- 7.39 (m , 43 5H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 65 m in LC /M S (E SI ) m /z; 307 [M +H ] H -N MR ( CD C l ) δ: 1. 60-1. 82 (m , 3H ), 1.92- 2.09 (m , 2H) , 2.95- 3.15 ( m, 2H) , 4. 18-4. 38 (m , 2H ) , 5. 15 (s, 2H ), 7. 20-7 .25 (m , 1H ) , 7. 25-7. 40 (m , 5H) , 7.50- 7.55 ( m, 1H ), 8.9 9 (s, 1H ), 9. 44-9. 71 (m , 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 90 m in LC /M S (E SI ) m /z; 365 [M +H ] TABLE 85 Rf D ata H -N MR (C DC l ) δ: 1. 02-1. 25 (m , 2H ), 1.44 (s, 9H ), 1. 52-1. 71 (m , 45 2H ), 1.78- 1.89 (m , 2H ), 2.02- 2.15 (m , 2H ), 2.52- 2.68 ( m, 1H ) , 3.17 ( s, 3H) , 3.35 -3.5 0 (m , 1H ), 3. 69 ( s, 3H ), 4. 28-4. 43 ( m, 1H ).

H -N MR (C DC l ) δ: 1. 26-1. 41 (m , 2H ), 1.46 (s, 9H ), 1. 52-1. 80 (m , 3H ), 2.00- 2.20 ( m, 3H) , 3. 49 (br s, 1H ) , 3. 82-3. 99 (m , 1H ), 4.46 ( br s, 1H ), 7.19-7. 25 (m , 1H ), 7. 46-7. 55 (m, 1H ), 9 .00 ( s, 1H ), 9.44- 9.85 46 ( m, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 84 m in LC /M S (E SI ) m /z; 345 [M +H ] LC /M S (E SI ) m /z; 343 [ M- H] LC /M S : condit i on 1, re tent ion ti m e = 2. 01 m in LC /M S (E SI ) m /z; 321 [M +H ] LC /M S : condit i on 1, re tent ion ti m e = 2. 18 m in 48 LC /M S (E SI ) m /z; 379 [M +H ] LC /M S (E SI ) m /z; 377 [ M- H] H -N MR ( CD C l ) δ: 0. 94-1. 13 (m , 2H ), 1.42- 1.71 (m , 4H) , 1.75- 1.93 ( m, 4H ), 2.55- 2.73 ( m, 1H ), 3. 10-3. 26 (m , 4H ) , 3. 32 ( s, 3H ), 3. 68 (s , 49 3H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 19 m in LC /M S (E SI ) m /z; 216 [M +H ] H -N MR ( CD C l ) δ: 1. 10-1. 30 (m , 2H ), 1.41- 1.78 (m , 3H) , 1.86- 2.12 ( m, 4H ), 3.25 (d, J = 6. 3 Hz, 2 H) , 3.35 ( s, 3H ), 3. 85-4. 02 ( m, 1H ) , 7. 15-7. 30 ( m, 1H ), 7. 45-7. 55 ( m, 1H ), 9. 00 ( s, 1H ), 9. 46 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 65 m in LC /M S (E SI ) m /z; 274 [M +H ] LC /M S (E SI ) m /z; 272 [ M- H] H -N MR ( CD C l ) δ: 1. 20-1. 41 (m , 1H ), 1.48- 1.70 (m , 4H) , 1.77- 1.92 ( m, 2H) , 2. 00-2. 13 (m , 1H ) , 2. 50-2. 73 (m , 1H ), 3.18 ( s, 3H ) , 51 3. 55-3. 78 ( m, 1H ), 3. 70 ( s, 3H ).

LC /M S : condit i on 1, re tent ion ti m e = 0. 60 m in LC /M S (E SI ) m /z; 189 [M +H ] H -N MR (CD C l ) δ: 1.22 (qd, J = 13.8, 2. 7 Hz, 2H ) , 1.55 (qd, J = 13. 8, 2.7 H z, 2H ), 1.86 (m , 2H ), 2.15 (m , 2H ), 2.64 (m , 1H ), 3. 14 (m , 52 1H ), 3. 17 ( s, 3H ), 3. 36 ( s, 3H ), 3. 70 ( s, 3H ).

LC /M S : condit i on 1, re tent ion ti m e = 1. 77 m in LC /M S (E SI ) m /z; 202 [M +H ] H -N MR ( CD Cl ) δ: 1. 50 (m , 4H) , 2.15 (m , 4H ) , 3 .21 ( tt , J = 10. 5, 3. 9Hz, 1H) , 3. 40 ( s, 3H ), 3.95 (t t , J = 11. 4, 3.6H z, 1H ) , 7.2 3 ( dd, J = 3. 3, 2.1 H z, 1H ), 7. 56 ( t, J = 2. 4 H z, 1H ), 9.03 (s, 1H ), 10. 9 ( br s, 53 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 35 m in LC /M S (E SI ) m /z; 260 [M +H ] LC /M S (E SI ) m /z; 258 [ M- H] TABLE 86 Rf D ata H -N MR ( CD C l ) δ: 1. 60-1. 95 (m , 6H ), 2.10- 2.30 (m , 2H) , 2.64- 2.83 ( m, 1H ), 3. 18 ( s, 3H ), 3. 71 ( s, 3H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 05 m in LC /M S (E SI ) m /z; 208 [M +H ] LC /M S : condit i on 1, re tent ion ti m e = 3. 60 m in LC /M S (E SI ) m /z; 184 [M +H ] H -N MR (C DC l ) δ: 1. 35-1. 88 ( m, 12H) , 2.73 -2.9 0 ( m, 1H ) , 3.17 (s , 3H ), 3. 69 ( s, 3H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 81 m in LC /M S (E SI ) m /z; 186 [M +H ] H -N MR (C D Cl ) δ : 1. 96 (m , 2H ), 2. 13 ( m, 2H ), 2.33 ( m, 2H ), 3.17 ( s, 3H) , 3.48 (m , 1H ), 3. 65 ( s, 3H ).

LC /M S : condit i on 1, re tent ion ti m e = 1. 85 m in LC /M S (E SI ) m /z; 144 [M +H ] H -N MR (C D Cl ) δ : 1. 57 (m , 2H ), 1. 78 ( m, 6H ), 3.10 ( m, 1H ), 3.19 ( s, 3H) , 3.69 (s , 3H) .

LC /M S : condit i on 1, re tent ion ti m e = 2. 94 m in LC /M S (E SI ) m /z; 158 [M +H ] H -N MR ( CD C l ) δ: 1. 28-1. 64 (m , 4H ), 1.83- 2.19 (m , 5H) , 2.57- 2.76 ( m, 1H ), 3. 18 ( s, 3H ), 3. 70 ( s, 3H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 74 m in LC /M S (E SI ) m /z; 240 [M +H ] H -N MR ( CD C l ) δ: 1. 45-1. 80 (m , 4H ), 1.82- 2.20 (m , 5H) , 2.81- 2.99 ( m, 1H ), 3. 17 ( s, 3H ), 3. 68 ( s, 3H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 77 m in LC /M S (E SI ) m /z; 240 [M +H ] H -N MR ( CD C l ) δ: 1. 75-2. 35 (m , 8H ), 3.94- 4.13 (m , 1H) , 7.20- 7.30 ( m, 1H ), 7. 46-7. 58 ( m, 1H ), 8.99 (s, 1H ), 9. 13 ( br s, 1H ). 61 LC /M S : condit i on 1, re tent ion ti m e = 3. 69 m in LC /M S (E SI ) m /z; 266 [M +H ] LC /M S (E SI ) m /z; 264 [ M- H] H -N MR (C D Cl ) δ: 1.16- 1.74 ( m, 7H ), 1.96 (ddd, J = 12.9, 5. 1, 3. 3 H z, 1H ), 2.36 ( br s, 1H ), 2. 86 (br s, 1H ) , 4. 31 ( m, 1H ), 7.24 (m , 1H ) , 7. 51 ( m, 1H ), 9. 01 ( s, 1H ), 9. 75 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 92 m in LC /M S (E SI ) m /z; 242 [M +H ] LC /M S (E SI ) m /z; 240 [ M- H] H -N MR (C D Cl ) δ: 1. 60-1. 82 ( m, 10H) , 2. 03 ( m, 2H ), 4.16 ( tt , J = 8. 7, 4.5 Hz, 1H ), 7. 24 ( m, 1H ), 7. 57 ( m, 1H ), 9.0 3 (s , 1H ) , 11. 18 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 4. 11 m in LC /M S (E SI ) m /z; 244 [M +H ] LC /M S (E SI ) m /z; 242 [ M- H] TABLE 87 Rf D ata H -N MR (C D Cl ) δ : 1. 95 (m , 1H ), 2. 14 ( m, 1H ), 2.38 ( m, 4H ), 4.60 ( quinｔ , J = 8. 4 H z, 1H ), 7. 28 ( m, 1H ), 7. 52 (m , 1H ) , 8.97 (s, 1H ) . 64 LC /M S : condit i on 1, re tent ion ti m e = 3. 22 m in LC /M S (E SI ) m /z; 202 [M +H ] LC /M S (E SI ) m /z; 200 [ M- H] H -N MR (C D Cl ) δ : 1. 76 (m , 4H ), 1. 91 ( m, 2H ), 2.03 ( m, 2H ), 4.36 ( m, 1H ), 7. 26 ( m, 1H ), 7 .55 (m , 1H ) , 9.03 (s, 1H ) , 10.43 (br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 64 m in LC /M S (E SI ) m /z; 216 [M +H ] H -N MR (D MS O- d ) δ: 1. 30-1. 60 (m, 4H) , 1. 90-2. 13 ( m, 4H) , 2. 20-2. 45 (m, 1H ), 3. 80-4. 00 (m , 1H ), 6.91- 7.05 (m , 1H ), 7.75- 7.90 ( m, 1H ), 8. 96 ( s, 1H ), 12. 47 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 4. 07 m in LC /M S (E SI ) m /z; 298 [M +H ] LC /M S (E SI ) m /z; 296 [ M- H] H -N MR (D MS O- d ) δ: 1. 50-1. 88 (m, 6H) , 1. 95-2. 11 ( m, 2H) , 2. 30-2. 45 (m, 1H ), 4. 05-4. 20 (m , 1H ), 6.90- 7.05 (m , 1H ), 7.75- 7.90 ( m, 1H ), 8. 93 ( s, 1H ), 12. 46 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 4. 00 m in LC /M S (E SI ) m /z; 298 [M +H ] LC /M S (E SI ) m /z; 296 [ M- H] H -N MR (C DC l ) δ: 1. 05 (s, 9H ), 1. 38 (dq, J = 10. 9, 3.0 H z, 4H) , 1. 65-1. 74 (m , 2H) , 1.86- 1.95 ( m, 2H ), 2.5 3-2. 65 (m , 1 H) , 3. 13 ( s, 3H ), 3. 56-3. 64 (m , 1H ), 3.6 7 (s, 3H ), 7. 32-7. 45 (m , 6H ), 7.64- 7.69 ( m, 4H ).

LC /M S : condit i on 1, re tent ion ti m e = 5. 45 m in LC /M S (E SI ) m /z; 426 [M +H ] H -N MR (C DC l ) δ: 1. 07 (s, 9H ), 1. 30-1. 45 (m , 2H ), 1. 52-1. 67 (m , 2H ), 1.89- 2.00 (m , 4H ), 3.60- 3.71 ( m, 1H ) , 3.89 ( tt , J = 1 2.2, 3 .0 H z, 1H ), 7.17 (dd, J = 3.6, 2. 0 Hz, 1H ), 7.33- 7.49 ( m, 7H ), 7 .65-7. 72 (m , 69 4H ), 8. 99 ( s, 1H ), 9. 11 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 5. 64 m in LC /M S (E SI ) m /z; 484 [M +H ] LC /M S (E SI ) m /z; 482 [ M- H] H -N MR (C D Cl ) δ: 1. 09 (s , 5H ), 1. 15 (s , 4H ), 1. 53-1. 97 (m , 5H ) , 1. 98-2. 08 ( m, 2H ) , 2.49 (dq, J = 12.6, 3. 0 Hz, 1H) , 3. 11 ( tt , J = 11. 2, 3. 3 H z, 0. 6H ), 3.25 (tt , J = 12.2, 3. 3 H z, 0. 4H ), 3.75- 3.85 (m, 0. 6H) , 4. 13-4. 18 (m , 0. 4H) , 6.71 ( dd, J = 3. 3, 2 .0 H z, 0.6H ), 7.01 (dd, J = 3. 0, 2.3 H z, 0 .4H ), 7. 16 (t, J = 3. 3 H z, 0. 6H ), 7.2 1-7. 28 (m , 0. 4H) , 70 7. 34-7. 47 ( m, 6H ) , 7.69- 7.75 (m , 4H ), 9.04 (br s , 1H ), 9. 18 ( s, 0. 6H ), 9. 24 ( s, 0.4H ) .

LC /M S : c ondi t ion 1, r etent i on t im e = 5.32, 5. 39 mi n ( ci s/t rans mi xt ure) LC /M S (E SI ) m /z; 496 [M +H ] LC /M S (E SI ) m /z; 494 [ M- H] TABLE 88 Rf D ata H -N MR ( CD C l ) δ: 1. 31-1. 46 (m , 1H ), 1.54- 1.67 (m , 4H) , 1.81- 1.99 ( m, 3H ), 2.02- 2.10 (m , 1H ), 2. 57-2. 79 (m , 1H) , 3.18 (d, J = 1. 3 H z, 71 3H ), 3. 70 ( d, J = 1 .7 H z, 3 H) , 3.98- 4.04 (m , 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 0. 86 m in (ci s/ tr ans m ixt ure) LC /M S (E SI ) m /z; 188 [M +H ] H -N MR (C D Cl ) δ: 0. 03-0. 05 ( m, 6H) , 0. 85 ( s, 4 H) , 0. 86 ( s, 5H ) , 1. 27-1. 52 (m , 4H) , 1.67- 1.82 ( m, 2H ), 1.9 3 (t d, J = 11.9, 3. 3 H z, 2H ), 2. 53-2. 66 ( m, 1H ), 3. 14 (s, 3H ), 3 .66 (s, 3H ) , 3.94- 3.98 (m , 1H ).

LC /M S : c ondi t ion 1, r etent i on t im e = 4.83, 5. 00 mi n ( ci s/t rans mi xt ure) LC /M S (E SI ) m /z; 302 [M +H ] H -N MR (C DC l ) δ: 0. 05 (s , 4H ), 0.08 ( s, 2H ), 0.90 ( s, 9H ), 1. 49-1. 83 ( m, 6H ), 1. 93-2. 08 ( m, 2H ), 3 .59- 3.69 (m, 0 .3H ), 3. 93 ( tt , J = 11 .2, 3.0 H z, 1H ), 4.02- 4.07 ( m, 0.7H ), 7.20- 7.26 (m , 1H ) , 7.52 ( dd, J = 4. 3, 2. 3 Hz, 1H ), 9. 01 (s, 0.7H ), 9.02 (s , 0. 3H) , 9. 78 (br s, 1H ).

LC /M S : c ondi t ion 1, r etent i on t im e = 5.07, 5. 14 mi n ( ci s/t rans mi xt ure) LC /M S (E SI ) m /z; 360 [M +H ] LC /M S (E SI ) m /z; 358 [ M- H] H -N MR (C D Cl ) δ: 0.11 (s , 3H ), 0.14 ( s, 3H ), 0.93 ( s, 4. 5H ), 0.98 ( s, 4. 5H ), 1.50- 1.81 ( m, 3H ), 1.83- 2.17 ( m, 4H ), 2.37 ( dq, J = 12. 9, 4. 0 H z, 1H ), 3. 15 (t t , J = 11. 9, 4.0 H z, 0. 5H) , 3.29 (t t, J = 12. 6, 4.0 H z, 0. 5H) , 3. 72-3. 84 ( m, 0.5H ), 4 .17 (br s, 0.5 H) , 6. 77 ( dd, J = 3. 6, 2. 0 H z, 0.5H ), 7. 12 (d d, J = 3.6, 2. 0 H z, 0.5H ) , 7. 24-7 .27 ( m, 0. 5H) , 74 7. 30 ( t, J = 3. 3 H z, 0. 5H ), 9. 13 ( br s, 1H ), 9. 22 ( s, 0. 5H) , 9. 23 (s , 0. 5H) .

LC /M S : c ondi t ion 1, r etent i on t im e = 4.88, 4. 97 mi n ( ci s/t rans mi xt ure) LC /M S (E SI ) m /z; 372 [M +H ] LC /M S (E SI ) m /z; 370 [ M- H] H -N MR (D MS O- d ) δ: 1. 35-1. 51 (m, 1H) , 1. 59-1. 71 ( m, 1H) , 1. 71-1. 86 (m , 2H) , 1.92- 2.03 ( m, 3H ), 3.1 0 (dt , J = 12.9, 3. 6 H z, 0. 7H) , 3.18 (dt , J = 15. 2, 3.0 Hz, 0.3H ), 3. 51-3. 63 ( m, 0. 7H ), 75 3. 92-3. 99 (m , 0.3H ), 4. 51 ( d, J = 2. 6 H z, 0. 3H) , 4.61 (d, J = 4.3 Hz, 0. 7H) , 6. 82 (d d, J = 3.3, 1.7 H z, 0.7H ), 6.97 (dd, J = 3. 3, 1. 7 H z, 0. 3H) , 7.48 (t , J = 3. 0 H z, 1H ), 9. 51 ( s, 0.7H ) , 9 .51 (s, 0. 3H ), 12.51 ( br s , 1H) .

H -N MR (C DC l ) δ: -0. 04 ( s, 9H ), 0. 94 (t, J = 8. 1 Hz, 2H) , 1.7 3 ( qd, J = 12. 4, 3.8 H z, 2H ), 2.00 (br s , 2H ), 3. 01 (t , J = 12.2 H z, 2 H) , 3.55 ( t, J = 8 .0 H z, 2H) , 4. 16 ( tt , J = 11. 4, 3. 6 H z, 2H ) , 4. 29 (br s, 2H) , 76 5. 12 ( s, 2H ), 5. 71 (s, 2H ) , 7.26 ( d, J = 3.6H z, 1H ) , 7.31- 7.40 (m , 5H ), 7. 57 ( d, J = 3 .6H z, 1H ), 9. 03 ( s, 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 3. 29 m in LC /M S (E SI ) m /z; 495 [M +H ] TABLE 89 Rf D ata H -N MR ( CD Cl ) δ: -0. 07 ( s, 9H ), 0. 91 (t , J = 8. 3 H z, 2H ), 1.27- 1.38 ( m, 3H ), 1 .97- 2.02 (m , 2H) , 2. 70-2. 74 ( m, 2H ), 3.53 (t , J = 8.3 H z, 2H ), 4. 02-4. 23 ( m, 3H ) , 5.10 (s, 2H ) , 5.64 (d, J = 2. 4Hz, 2 H) , 6.61 ( d, J = 3. 3Hz, 1H) , 7.26- 7.33 (m , 6H ), 8.85 (s , 1H) .

LC /M S : condit i on 3, re tent ion ti m e = 2. 26 m in LC /M S (E SI ) m /z; 496 [M +H ] LC /M S : condit i on 3, re tent ion ti m e = 3. 05 m in LC /M S (E SI ) m /z; 506 [M +H ] LC /M S : condit i on 3, re tent ion ti m e = 1. 55 m in LC /M S (E SI ) m /z; 366 [M +H ] LC /M S : condit i on 3, re tent ion ti m e = 0. 70 m in LC /M S (E SI ) m /z; 231 [M +H ] LC /M S : condit i on 3, re tent ion ti m e = 1. 63 m in 81 LC /M S (E SI ) m /z; 389 [M +H ] LC /M S (E SI ) m /z; 387 [ M- H] LC /M S : condit i on 3, re tent ion ti m e = 1. 08 m in 82 + + LC /M S (E SI ) m /z; 390 [M +H ] H -N MR (C D Cl ) δ: 3. 20 (s , 3H ), 3. 65 (s , 3H ), 3. 68-3. 70 (m , 1H ) , 4. 14 (t , J = 8.7 H z, 2H ) , 4. 22 ( d, J = 6.0 H z, 2H ), 5. 09 ( s, 2H) , 83 7. 30-7. 36 ( m, 5H ).

LC /M S : condit i on 3, re tent ion ti m e = 1. 88 m in LC /M S (E SI ) m /z; 279 [M +H ] H -N MR (C DC l ) δ: 4. 31-4. 41 (m , 4H ), 4.62- 4.69 (m , 2H ), 5.11 (s , 2H ), 7. 27-7. 36 ( m, 6H ), 7. 55 ( dd, J = 3. 6, 2.4 H z, 1H) , 8.9 5 (s, 1H ) , 84 9. 18 ( br s, 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 2. 09 m in LC /M S (E SI ) m /z; 337 [M +H ] H -N MR (C D Cl ) δ: 1.88 ( br s, 1H ). 3.3 5 (s, 3H ), 3.55 ( s, 3H ), 4.74 ( s, 2H) , 7.39 (d, J = 8. 1 H z, 2H ), 7. 67 ( d, J = 8.1 Hz, 2H) .

LC /M S : condit i on 1, re tent ion ti m e = 0. 84 m in LC /M S (E SI ) m /z; 196 [M +H ] H -N MR (C DC l ) δ: 0. 11 ( s, 6H ), 0 .95 (s, 9H) , 3.3 5 ( s, 3H ), 3.55 (s , 3H ), 4. 77 ( s, 2H ), 7. 35 ( d, J = 8. 1 H z, 2H ) , 7.65 (d, J = 8.1 H z, 2H ).

LC /M S : condit i on 1, re tent ion ti m e = 4. 73 m in LC /M S (E SI ) m /z; 310 [M +H ] H -N MR (C DC l ) δ: 0. 12 (s, 6H ), 0. 96 (s, 9H) , 4. 83 (s, 2H ) , 7. 00 (dd, J = 3.9, 2.1 Hz, 1H ), 7.47 ( d, J = 8.1 Hz, 2H ), 7.49 ( m, 1H ), 8. 14 (d, J = 8.1 Hz, 2 H) , 9.04 (s , 1H) , 9.59 (br s, 1H ) .

LC /M S : condit i on 1, re tent ion ti m e = 4. 80 m in LC /M S (E SI ) m /z; 368 [M +H ] LC /M S (E SI ) m /z; 366 [ M- H] H -N MR (C DC l ) δ: 0. 15 (s, 6H ), 0. 98 (s, 9H) , 4. 84 (s, 2H ) , 6. 97 (dd, J = 3. 3, 2.1 H z, 1H ), 7. 27 (dd, J = 6. 0, 3.3 H z, 1H ), 7. 50 (d , J = 8.4 88 H z, 2H ), 7. 98 ( d, J = 8. 4 H z, 2H ), 9. 22 (br s, 1H ), 9 .30 (s, 1H ) .

LC /M S : condit i on 1, re tent ion ti m e = 4. 93 m in LC /M S (E SI ) m /z; 380 [M +H ] TABLE 90 Rf D ata H -N MR ( CD C l ) δ: 1. 58 ( m, 4H ), 1. 73 ( m, 5H ), 2.8 0 (t t, J = 8. 4, 3.6 H z, 1H ), 3. 17 ( s, 3H ), 3. 62 ( m, 2H ), 3. 69 ( s, 3H ).

LC /M S : condit i on 1, re tent ion ti m e = 1. 42 m in LC /M S (E SI ) m /z; 202 [M +H ] H -N MR (C D Cl ) δ : 0. 04 (s, 6H ), 0.89 ( s, 9H ) , 1. 55 (m , 4H ), 1.69 ( m, 5H) , 2. 80 (t t, J = 7.8, 4.2 H z, 1H ), 3.17 ( s, 3H ) , 3. 58 (d, J = 90 10. 5 H z, 2H ), 3. 68 ( s, 3H ).

LC /M S : condit i on 1, re tent ion ti m e = 5. 08 m in LC /M S (E SI ) m /z; 316 [M +H ] H -N MR (C DC l ) δ: 0.06 ( s, 6H ), 0.90 ( s, 9H ) , 1.71 ( m, 7H ), 1. 90 (m , 2H ), 3.53 (d, J = 6.9 H z, 2H ), 4.07 (m , 1H ) , 7.20 (d d, J = 3. 3 2. 1 Hz, 1H ), 7. 50 ( t, J = 3. 3 H z, 1H ), 8. 98 ( s, 1H ), 9. 42 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 5. 19 m in LC /M S (E SI ) m /z; 374 [M +H ] LC /M S (E SI ) m /z; 372 [ M- H] H -N MR (C DC l ) δ: 0.08 ( s, 6H ), 0.93 ( s, 9H ) , 1.22 ( m, 2H ), 1. 70 (m , 1H ), 1. 90-2. 05 (m, 4H) , 2.15 (m , 2H ), 3 .16 (m , 1H ), 3. 51 ( d, J = 6.6 H z, 2H ), 6. 08 H z ( m, 1H ) , 7.27 (m , 1H ), 9.16 (br s, 1H ) , 9.22 (s, 1H ) .

LC /M S : condit i on 1, re tent ion ti m e = 5. 09 m in LC /M S (E SI ) m /z; 428 [M +H ] LC /M S (E SI ) m /z; 426 [ M- H] LC /M S : condit i on 1, re tent ion ti m e = 3. 62 m in LC /M S (E SI ) m /z; 202, 2 04 [ M+H ] H -N MR (C DC l ) δ: 1.83- 2.04 (m , 4H ) , 2.25 ( td, J = 11. 6, 2. 5 H z, 2H ), 2. 93 (d, J = 11.7 Hz, 2H ), 3. 59 (s, 2H ), 3.92- 3.99 (m, 1H ), 7.24 ( dd, J = 3. 6, 2. 1 Hz , 1H ), 7.47 (d, J = 8. 1 Hz, 2H ), 7. 50 (dd, J = 3. 6, 2. 4 H z, 1H ), 7. 61 ( d, J = 8. 1 H z, 2H ), 8.98 (s, 1H ) , 9.04 (br s, 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 1. 25 m in LC /M S (E SI ) m /z; 346 [M +H ] H -N MR ( CD Cl ) δ: -0. 06 ( s, 9H ), 0. 91 (t , J = 8. 3 H z, 2H ), 1.78- 2.04 ( m, 4H ), 2.25 ( td, J = 11. 6, 2. 8 H z, 2H ) , 2. 93 (d , J = 11. 7 H z, 2H ) , 3. 53 (t , J = 8. 3 Hz, 2H ), 3 .60 (s , 2H ), 3. 95 (t t, J = 11.4 , 3. 9 Hz, 1H) , 95 5. 68 (s, 2H ), 7.23 ( d, J = 3. 3 H z, 1H ) , 7. 47 (d, J = 8.1 H z, 2H ), 7.53 ( d, J = 3. 6 H z, 1H ), 7.61 (d, J = 8.7 H z, 2H ), 8. 99 ( s, 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 2. 19 m in LC /M S (E SI ) m /z; 476 [M +H ] H -N MR (C D Cl ) δ: - 0.07 (s, 9H ), 0.90 ( t, J = 8. 1 H z, 2H ) , 1. 23 ( d, J = 14. 4 H z, 1H ), 1 .31-1. 53 (m , 2H ), 1.78-2. 01 (m , 6H ), 2.73 (d, J = . 5 H z, 1H ) , 2.89 (d, J = 11.4 H z, 1H ), 3. 49 (s, 2H ) , 3.54 ( t, J = 8.1 H z, 2H ), 4. 05 ( d, J = 7.5 H z, 1H ), 5. 65 ( d, J = 2.1 H z, 2H ), 6. 63 ( d, J = 3.6 H z, 1H ) , 7. 32 (d, J = 3. 6 H z, 1H) , 7. 41 (d, J = 8.1 H z, 2H) , 7. 57 ( d, J = 8. 1 H z, 2H ) , 8.86 (s, 1H ) .

LC /M S : condit i on 3, re tent ion ti m e = 1. 64 m in LC /M S (E SI ) m /z; 477 [M +H ] LC /M S : condit i on 3, re tent ion ti m e = 2. 15 m in LC /M S (E SI ) m /z; 487 [M +H ] TABLE 91 Rf D ata H -N MR (C DC l ) δ: 2. 05-2. 20 (m , 2H ), 3.20 (s, 3H ), 3. 39-3. 80 (m , 8H ), 5. 14 ( s, 2H ), 7. 28-7. 39 ( m, 5H ).

LC /M S : condit i on 3, re tent ion ti m e = 2. 02 m in LC /M S (E SI ) m /z; 293 [M +H ] LC /M S : condit i on 3, re tent ion ti m e = 2. 13 m in 99 LC /M S (E SI ) m /z; 351 [M +H ] LC /M S (E SI ) m /z; 349 [ M- H] H -N MR ( CD C l ) δ: 2.74 (br s, 2H ), 2. 96 (d, J = 12. 0 H z, 1H ), 3.54 ( d, J = 12. 0 H z, 1H ), 7. 35 (d, J = 9.0 Hz, 2H ), 7.50 ( d, J = 9. 0 H z, 100 2H ).

LC /M S : condit i on 1, re tent ion ti m e = 0. 78 m in LC /M S (E SI ) m /z; 240, 2 42 [ M+H ] H -N MR ( CD C l ) δ: 2.69 (br s, 1H ), 3. 02 (d, J = 13. 2 H z, 1H ), 3.52 ( d, J = 13. 2 H z, 1H ), 7. 38 (m, 3H) , 7.57 (m , 2H) .

LC /M S : condit i on 1, re tent ion ti m e = 0. 55 m in LC /M S (E SI ) m /z; 206 [M +H ] H -N MR (C D Cl ) δ: 2. 97 (d, J = 12. 9 H z, 1H ), 3.57 ( d, J = 13. 2 H z, 1H ), 7. 08 ( m, 2H ), 7 .55 (m , 2H) .

LC /M S : condit i on 1, re tent ion ti m e = 0. 56 m in LC /M S (E SI ) m /z; 224 [M +H ] H -N MR (C D Cl ) δ : 2. 77 (ddd, J = 5 .5, 2.5, 1.2 H z, 1H) , 3. 19 ( ddd, J 103 = 5. 5, 4.0, 1.1 H z, 1H ) , 3. 92 (dd, J = 4.0, 2. 5 Hz, 1H) , 7. 40 (d, J = 8. 3 H z, 2H ), 7. 61 ( d, J = 8. 3 H z, 2H ).

H -N MR (C D OD ) δ: 1.91 ( s, 3H ) , 2. 20- 2.33 ( m, 4H ), 3.20-3. 30 (m , 2H ), 3.50- 3.69 (m , 3H ), 6. 95 (d, J = 3 .3 H z, 1H ), 7. 43 (d, J = 3 .3 Hz , 1H ), 9. 34 ( s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 2. 15 m in LC /M S (E SI ) m /z; 243 [M +H ] LC /M S (E SI ) m /z; 241 [ M- H] TABLE 92 Rf D ata H -N MR ( C DC l ) δ: 4.87 (s, 2H ), 7. 11 ( d, J = 8.9 Hz, 2H ) , 7 .92 (d , J = 8.9 H z, 2H ), 9 .95 (s , 1H ).

H -N MR ( DM S O- d ) δ: 4 .72 (s, 2H ), 7. 38 ( br s , 1H ) , 7 .50 (d, J = 8 .1 H z, 2H) , 7. 83 (d, J = 8 .1 H z, 2H) , 7. 97 (br s, 1 H) .

LC /M S : condi ti on 3, r etent ion t im e = 1. 48 m in LC /M S (E SI ) m /z; 213, 215 [ M+H ] H -N M R ( C D C l ) δ : 4. 49 ( s, 2H ) , 7. 73 - 7. 81 (m , 2 H ) , 7. 87 ( s, 1 H ).

H -N MR (C D Cl ) δ: 4. 48 (s, 2H ), 7. 74- 7.84 ( m, 3H) .

H -N MR (C DC l ) δ: 4. 50 (s, 2H ), 7. 70 (d, J = 8.7 H z, 1H ) , 7.81- 7.84 ( m, 2H ).

H -N MR (C D Cl ) δ: 1.4 3 (s, 9H) , 2. 87 (t , J = 6. 9 H z, 2H ), 3.39 ( q, J 110 = 6 .9 H z, 2H ) , 4. 54 (br s , 1H ), 7.3 1 ( d, J = 8. 6 Hz, 2H ), 7.58- 7.62 ( m, 2H ).

H -N MR (C D Cl ) δ: 2.83 (q, J = 6. 9 H z, 2H ) , 2. 97-3. 04 (m , 2H) , 7. 27-7. 37 ( m, 2H ), 7. 58-7. 65 ( m, 2H ).

H -N MR ( CD C l ) δ: 1 .48 (s, 9H ), 4. 70 (s, 4H ).

H -N MR (C DC l ) δ: 1.44 (s , 9H ), 1.52 ( s, 3H ), 1.99 ( s, 1H ), 3.82 ( d, 113 J = 8.9 H z, 2 H) , 3.86 (d, J = 8. 9 H z, 2H ).

H -N MR (C D Cl ) δ: 4. 06 ( d, J = 12. 5 Hz, 2H ), 4. 23 (d, J = 12.

H z, 2H ) , 7. 96 (s, 1H ), 9.76 ( br s, 2H ).

H -N MR ( C DC l ) δ: 1.44 (s, 9H ), 3. 77 ( d, J = 8.6 Hz, 1H ) , 3 .85 116 (d , J = 8. 6 H z, 1H ) 3. 85-3. 92 (m , 2H ), 4.06- 4.15 (m , 2H) , 4 .30 - 4.40 ( m, 1H) .

H -N MR (C D Cl ) δ: 3. 01 ( d, J = 13. 2 Hz, 1H ), 3. 62 (d, J = 13. 2 H z, 1H) , 7 .35 ( m, 1H ), 7.93 ( m, 1H ), 8.60 (m , 1H ), 8. 78 (s , 1 118 H ).

LC /M S : condi ti on 3, r etent ion t im e = 0. 39 m in LC /M S (E SI ) m/ z; 20 7 [ M+ H ] H -N MR ( C DC l ) δ: 2.49 (s, 3H ), 2. 98 ( d, J = 13.2 H z, 1 H) , 3.5 2( d, J = 13. 2 H z , 1H ), 7.2 5 ( d, J = 8. 1 H z, 2H ) , 7. 48 ( d, J = 119 8. 1Hz, 2H ).

LC /M S : condi ti on 3, r etent ion t im e = 1. 44 m in LC /M S (E SI ) m/ z; 25 2 [ M+ H ] H -N MR (C D Cl ) δ: 2. 98 ( d, J = 13. 2 Hz, 1H ), 3. 55 (d, J = 13. 2 H z, 1H ), 3. 94 (s, 3H ) 6.76 (d, J = 8. 7 H z, 1H) , 7.7 7 (dd, J 120 = 8.1, 2.4 H z, 1H, 8.3 1 (d, J = 2. 4 H z, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 0. 54 m in LC /M S (E SI ) m/ z; 23 7 [ M+ H ] H -N MR (C D Cl ) δ: 3. 02 ( d, J = 13. 5 Hz, 1H ), 3. 37 (d, J = 13.

H z , 1H ) , 3. 77 ( s, 3H ), 6. 88 ( d, J = 9. 0 H z, 2H ) , 7. 45 ( d, J = 9 .0 H z, 2H) .

TABLE 93 R f Data H - NMR (C DC l ) δ : 3 .02 (d, J = 12 .9 H z , 1 H ), 3.50 (d, J = 1 3. 12 2 5 H z, 1H) , 3 .88 (s, 3H ), 3.9 1 ( s , 3 H ), 6.8 6 (d, J = 8.7 H z, 1H ), 7 .04 (m, 1H ) , 7 .17 (d, J = 1.8 Hz, 1H ).

H - NMR (CD C l ) δ : 1 .34 ( t, J = 7 .2 H z , 3 H) , 4 .26 (q, J = 7. 2 H z , 2H ), 6.3 5 (d , J = 15 .9 H z, 1H) , 7.0 7 (m , 2H ), 7.51 ( m , 2H ), 7.64 (d , 12 3 J = 1 5.9 H z , 1H ).

LC /M S: co ndi tion 1, ret enti on time = 4.17 mi n LC /M S(ESI ) m /z; 195 [M+ H ] H - NMR (C D C l ) δ: 1.2 8 (m , 4 H), 1.5 7 (m, 1H) , 1 .84 (m, 1H ) , 2 . 12 4 5 0(m , 1 H) , 4 .1 7 (q , J = 7 .2 H z , 2H) , 6. 96 (m , 2H ) , 7 .07 (m , 2 H ).

LC /M S: co ndi tion 1, ret enti on time = 4.42 mi n 12 5 LC /M S(ESI ) m/z ; 2 96 [M+ H ] H - NMR (C DC l ) δ: 0.8 5 (m, 2H ) , 1.2 2 (m, 1H ), 1.7 1 ( m, 3H ), 2.7 2 12 6 (m, 2H ), 6.8 9- 7. 05 (m , 4H) .

LC /M S: co ndi tion 1, ret enti on time = 0.33 mi n 12 7 LC /M S(ESI ) m /z; 168 [M+ H ] H - NMR ( CDC l ) δ: 1 .52-1 .80 (m , 9H ), 2.05 - 2.25 (m , 3H ), 3.6 0-3.7 5 12 8 (m, 1H ), 4.9 0- 5. 15 (m , 1H) , 5 .10 (s , 2H ), 7 .25- 7 .45 (m, 5 H) . a LC /M S: co ndi tion 1, ret enti on time = 3.63 mi n LC /M S(ESI ) m /z; 302 [M+ H ] H - NMR ( CDC l ) δ: 1 .41-1 .53 (m , 3H ), 1.53 - 1.91 (m , 7H ), 2.0 1-2.2 5 (m, 3H ), 3. 73- 3. 86 (m , 1H ), 4.98 -5.02 ( m, 1 H) , 5.1 0 ( s, 2H ), 12 8 7.2 8-7.4 3 (m , 5H ).

LC /M S: co ndi tion 1, ret enti on time = 3.63 mi n LC /M S(ESI ) m /z; 302 [M+ H ] H - NMR ( DMSO-d ) δ: 1.2 0 (d, J = 12 .3 Hz , 2 H ) , 1 .57 ( m , 5 H), 1.7 2 (s, 1H ) , 1.9 2-1.9 6 ( m , 5H ), 2 .83 (s, 1 H) , 4 .26 ( br s, 1H ) . 12 9 LC /M S: co ndi tion 1, ret enti on time = 0.33 mi n LC /M S(ESI ) m /z; 168 [M+ H ] H - NMR ( DM SO-d ) δ: 1.27 (d , J = 12.7 Hz , 2 H ), 1 .41-1 .63 (m, 6H ), 1.7 6-2.0 2 (m , 5H ), 2.7 5- 2.8 0 (b r s, 1 H ). 13 0 LC /M S: co ndi tion 1, ret enti on time = 0.33 mi n LC /M S(ESI ) m /z; 168 [M+ H ] 13 1 H - NMR (C D OD ) δ : 4.0 3 ( d d, J = 13. 5, 1 2.9 H z, 2H ).

LC /M S: co ndi tion 1, ret enti on time = 4.18 mi n 13 2 LC /M S(ESI ) m/z ; 3 02 [M+ H ] H -N M R (C D Cl ) δ: 0 .0 4 ( s , 9H ) , 0. 89 ( s , 6 H ), 1 .5 2- 1. 57 (m , 5 13 3 H ),1.6 3- 1 .72 (m, 5H) , 3.1 7 (s, 3H ), 3.5 5 ( d, J = 6.9 H z , 2 H ) , 3 . 68 ( s, 3H ).

H - NMR (C DC l ) δ: -0.0 4 ( s, 6H) , 0 .85 (s, 9H ), 1 .43- 1.77 (m , 8 H ), 1 .8 0- 1 .94 ( m , 2 H ), 3.4 9 (d, J = 6 .9 H z, 2 H ), 7 .16 ( d d, J 13 4 = 3. 6, 2 . 1 Hz , 1 H ), 7 .1 6 ( dd , J = 3 . 6, 2 . 7 H z , 1 H) , 8 .9 5 ( s, 1 H ), 9. 16 ( br s , 1 H).

TABLE 94 Rf D ata H -N MR ( CD C l ) δ: -0. 06 (s , 6H ) , 0 .83 ( s, 9 H) , 1.61- 2.15 (m , 9H ), 3. 29- 3.37 (m , 1H ) , 3.56 (d, J = 6. 6 H z, 2H) , 6.72 (dd , J = 3. 3 2 .1 H z, 1 H) , 7.22 (t , J = 3. 3 H z, 1H ) , ), 9. 04 ( s, 2H ) , 9 .17 (b r s, 1H) .

LC /M S : condi ti on 3, r etent ion t im e = 3. 22 m in LC /M S (E SI ) m /z; 386 [ M+H ] LC /M S (E SI ) m/ z; 384 [M -H ] H -N MR (C DC l ) δ: 0. 08 ( s, 6H ), 0. 93 (s, 9H) , 1.20 ( qd, J = 12. 2, 3. 6 H z, 2H ) , 1.7 6-1.61 ( m, 1H ), 2.05- 1.84 (m , 4H ), 2.19- 2. 09 (m , 2H ), 3.16 (t t , J = 1 2.2, 3 .6 H z, 1H ), 3.52 ( d, J = 6. 3 H z, 2H ) , 6.81 135 ( dd, J = 3. 3, 2. 0 Hz, 1 H) , 7.29 (t , J = 3. 3 H z, 1H ), 9. 21 (br s, 1H) , b 9. 23 ( s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 3. 20 m in LC /M S (E SI ) m /z; 386 [ M+H ] LC /M S (E SI ) m / z; 384 [ M- H] LC /M S : condi ti on 1, r etent ion t im e = 0. 32 m in LC /M S (E SI ) m/ z; 20 1 [ M+ H ] LC /M S : condi ti on 1, r etent ion t im e = 0. 34 m in LC /M S (E SI ) m /z; 215 [ M+H ] H -N MR (C DC l ) δ: 1. 46 (s, 9H ), 4. 58-4. 65 (m , 2H ), 4. 68-4. 74 (m , 2H ), 5. 36-5. 41 (m, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 3. 44 m in LC /M S (E SI ) m /z; 195 [ M+H ] H -N MR ( CD Cl ) δ: 1.56- 1.75 (m , 6H ), 1. 82-1. 96 ( m, 6H) , 2.22- 2.28 ( m, 2H ), 3. 17 ( s, 3H ), 3. 68 ( s, 3H ).

LC /M S : condi ti on 3, r etent ion t im e = 2. 84 m in LC /M S (E SI ) m /z; 240 [ M+H ] H -N MR ( CD Cl ) δ: 1.50- 1.97 (m , 8H ), 2. 10-2. 27 ( m, 6H) , 2.33- 2.38 ( m, 2H) , 6.96- 6.99 ( m, 1H ), 7.43- 7.47 ( m, 1H ), 8.9 3 (s, 1H ), 9.25 ( br s, 1H) .

LC /M S : condi ti on 3, r etent ion t im e = 3. 17 m in LC /M S (E SI ) m /z; 298 [ M+H ] LC /M S (E SI ) m / z; 296 [ M- H] TABLE 95 E x D ata H -N MR (C DC l ) δ: 1. 41-1. 52 (m , 3H ), 1. 77-1. 91 (m , 7H ), 2.72 (s , 3H ), 2. 97-3. 05 (m , 1H) , 6.64 (d, J = 2.3 H z, 1H ), 7. 06 ( d, J = 2.6 H z, 1 1H ), 8. 29 ( s, 1H ), 8. 80 ( br s, 1H ).

LC /M S: con dit io n 1, ret enti on ti m e = 1. 96 mi n LC /M S( ES I ) m /z; 255 [M +H ] H -N MR ( CD C l ) δ: 1.39- 1.53 ( m, 3H) , 1. 77-1. 95 (m , 7H ), 2.95- 3.11 (m, 1H ), 6.60 ( d, J 2 = 3.3 H z, 1H) , 7.1 2 ( d, J = 3. 0 H z, 1H ), 8.28 (s, 1H ) , 8.69 (s, 1H ).

LC /M S: con dit io n 1, ret enti on ti m e = 2. 84 mi n LC /M S( ES I ) m /z; 241 [M +H ] LC /M S: con dit io n 1, ret enti on ti m e = 3. 56 mi n LC /M S( ES I ) m /z; 376 [M +H ] LC /M S: con dit io n 1, ret enti on ti m e = 0. 96 mi n LC /M S( ES I ) m /z; 309 [M +H ] H -N MR ( CD Cl ) δ: 2. 46 ( s, 3H ), 6.6 0 ( dd, J = 3. 3, 2.4 H z, 1H ) , 7. 18-7. 23 ( m, 1H ), 7. 28-7. 43 ( m, 3H ) , 7.54- 7.63 (m , 1H ), 9. 04 ( br s , 1H ), 9. 32 ( s, 1H ).

LC /M S: con dit io n 1, ret enti on ti m e = 3. 87 mi n LC /M S( ES I ) m /z; 250 [M +H ] LC /M S( ES I ) m /z; 248 [ M-H ] H -N MR ( CD Cl ) δ: 1. 31-1. 69 (m, 3H ) , 1.72- 1.86 (m , 2H) , 1.87- 2.01 (m , 3H ) , 2. 02-2. 16 (m , 2H ), 3.07- 3.29 ( m, 1H ), 6. 81 ( dd, J = 3.3, 2. 1Hz, 1H ), 7.29 (t , J = 3. 0 H z, 1H ), 9. 23 (s, 1H ), 9. 33 (br s, 1H ).

LC /M S: con dit io n 1, ret enti on ti m e = 3. 92 mi n LC /M S( ES I ) m /z; 242 [M +H ] LC /M S( ES I ) m /z; 240 [ M-H ] LC /M S: con dit io n 1, ret enti on ti m e = 4. 12 mi n 7 LC /M S( ES I ) m /z; 256 [M +H ] LC /M S( ES I ) m /z; 254 [ M-H ] H -N MR (D MS O -d ) δ: 1.1 5-1.5 5 (m, 3H ), 1.60- 1.92 (m , 7H ) , 2. 85-3. 10 ( m, 1 H) , 6.57 ( s, 1H ), 7. 17 (t , J = 3. 0 Hz, 1H ), 8. 64 (s, 1H ) , 12. 04 ( s, 1H) , 12. 96 (br s, 1H ) .

LC /M S: con dit io n 1, ret enti on ti m e = 3. 79 mi n LC /M S( ES I ) m /z; 273 [M +H ] LC /M S( ES I ) m /z; 271 [ M-H ] H -N MR (D MS O -d ) δ: 1.0 7-1.6 4 (m, 5H ), 1.65- 1.89 (m , 5H ) , 2. 67-2. 84 (m, 1H ), 6.33 ( s, 1H) , 6. 93 (d, J = 2.7 H z, 1H ), 8.01 ( d, J = 9 1. 2 H z, 1H ), 10. 76 ( s, 1H ), 11. 63 ( s, 1H) .

LC /M S: con dit io n 1, ret enti on ti m e = 3. 62 mi n LC /M S( ES I ) m /z; 257 [M +H ] H -N MR ( CD Cl ) δ: 1. 16-1. 40 (m, 3H ) , 1.61- 1.82 (m , 1H) , 1.85- 2.09 (m , 4H ), 2. 10-2. 26 (m , 2H ), 3.09- 3.25 (m , 1H) , 3.58 (t , J = 6.0 H z, 2H ), 6.74- 6.85 (m , 1H) , 7. 20-7. 32 (m , 1H ), 9. 04 (br s, 1H ), 9.22 ( s, 1H ).

LC /M S: con dit io n 1, ret enti on ti m e = 2. 99 mi n LC /M S( ES I ) m /z; 272 [M +H ] LC /M S( ES I ) m /z; 270 [ M-H ] TABLE 96 E x D ata H -N MR (C DC l ) δ: 0. 86 (d, J = 6. 5 H z, 3H ) , 1.48 ( br s, 9H ), 1.87 ( d, J = 12.3 H z, 1H) , 2. 04-2. 11 (m , 1H ), 2.23 -2.3 9 (m, 2H ), 2.92 ( td, J = 11. 0, 4.5 H z, 2H ), 3. 17 ( t, J = 11. 0 H z, 1H) , 3.48 (d, J = 7. 0 Hz, 1H ) , 11 7. 24-7. 32 ( m, 2H ), 9. 18 ( br s, 1H ), 9. 22 ( s, 1H) .

LC /M S : condit i on 1, re tent ion ti m e = 4. 05 m in + t + LC /M S (E SI ) m /z; 301 [M - B u] LC /M S (E SI ) m /z; 355 [ M- H] LC /M S : condit i on 1, re tent ion ti m e = 3. 09 m in LC /M S (E SI ) m /z; 324 [M +H ] H -N MR (C DC l ) δ: 1. 18-1. 29 (m , 1H ), 1.49 (s, 9H ), 1. 63-1. 77 (m , 1H ), 1.90 ( dt, J = 13. 9, 3. 0 Hz, 1H ), 2.09- 2.33 (m , 2H ), 2.87 ( t, J = 13. 2 H z, 1H ), 3.30 (t t, J = 11. 6, 4. 3 H z, 1H ), 4. 23 (br s, 1 H) , 4.44 ( br s, 1H ), 6.92 ( br s , 1H ), 7. 31 (t , J = 3 .3 H z, 1H ), 9 .23 ( s, 1H ) , 9. 27 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 79 m in + t + LC /M S (E SI ) m /z; 287 [ M- Bu ] LC /M S (E SI ) m /z; 341 [ M- H] H -N MR (C D Cl ) δ: 1. 68-1. 80 ( m, 1H) , 1. 93 ( d, J = 13. 5 H z, 1H ), 2. 14-2. 37 ( m, 2H ), 2.95 (br s , 1H) , 3. 07-3. 22 ( m, 1 H) , 3.26- 3.38 (m , 1H ), 4.33 (br s , 1H ), 4. 55 (br s, 1H ), 5. 20 (d, J = 5 .9 H z, 2H ) , 14 6. 95-7. 17 ( m, 1H ), 7. 28-7. 43 ( m, 6H ), 9. 22 ( s, 1H ), 9. 39 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 84 m in LC /M S (E SI ) m /z; 377 [M +H ] LC /M S (E SI ) m /z; 375 [ M- H] H -N MR ( CD OD ) δ: 1. 71-1. 93 ( m, 3H ), 2.0 1-2. 24 (m , 2H ), 2.70- 2.81 ( m, 1H ), 2.94- 3.17 (m , 2H ), 3. 37-3. 47 (m , 1H) , 6.91 (d, J = 3. 3 H z, 1H ), 7. 41 ( d, J = 3 .0 H z, 1 H) , 9.32 (s, 1H) .

LC /M S : condit i on 1, re tent ion ti m e = 0. 35 m in LC /M S (E SI ) m /z; 243 [M +H ] LC /M S (E SI ) m /z; 241 [ M- H] LC /M S : condit i on 1, re tent ion ti m e = 0. 40 m in LC /M S (E SI ) m /z; 333 [M +H ] LC /M S : condit i on 1, re tent ion ti m e = 3. 25 m in 17 LC /M S (E SI ) m /z; 353 [M +H ] LC /M S (E SI ) m /z; 351 [ M- H] H -N MR ( CD Cl ) δ: 1.23- 1.35 (m , 4H ) , 1. 85-1. 96 ( m, 2H ), 2.20 (m , 1H ), 2.50 (t , J = 11.6 H z, 1H ), 3 .01 (d, J = 10. 9 Hz, 1H) , 3. 16 ( d, J = . 9 H z, 1H ), 3. 41-3. 53 ( m, 1H ), 6. 71 (dd, J = 3.3, 2 .0 Hz, 1H ) , 7. 22-7. 31 ( m, 2H ) , 7.70 ( d, J = 7.6 H z, 1H ), 8.50 (dd, J = 4.6, 2. 0 H z, 1H ), 8. 60 ( d, J = 2. 0 H z, 1H ), 9. 21 (s, 1H ), 9.32 (br s, 1H ) .

LC /M S : condit i on 1, re tent ion ti m e = 0. 35 m in LC /M S (E SI ) m /z; 334 [M +H ] LC /M S (E SI ) m /z; 332 [ M- H] TABLE 97 E x D ata H -N MR ( CD C l ) δ: 1. 23-1. 29 (m , 1H ), 1.85- 1.96 (m , 3H) , 2.13- 2.27 ( m, 2H ), 2. 49 ( t , J = 1 1.2 Hz, 1H) , 3.0 5 ( d, J = 10.2 Hz, 1H) , 3.20 ( d, J = 10. 9 H z, 1H ) , 3.41- 3.53 (m , 1H ), 6.75 (dd, J = 3.3, 2. 0 Hz, 1H) , 19 7. 23-7. 29 ( m, 1H ), 8. 74 ( s, 1H ), 9. 19 ( br s, 1H) , 9.2 1 (s , 1H) .

LC /M S : condit i on 1, re tent ion ti m e = 0. 35 m in LC /M S (E SI ) m /z; 340 [M +H ] LC /M S (E SI ) m /z; 338 [ M- H] H -N MR (D MS O -d ) δ: 1. 62-1. 79 ( t, J = 12.6 Hz, 1H ), 1.8 1-1. 92 (m , 1H ), 1.95- 2.11 (m, 1H ), 2.12- 2.24 ( m, 1H ), 3.07 ( t, J = 1 2.6 H z, 1H ) , 3. 21 (m , 1H) , 4.37 (d, J = 12. 6 H z, 1H) , 4.57 (d, J = 11. 6 H z, 1H) , 6. 99 ( s, 1H ), 7. 53 ( s, 1H ) , 8.95 (br s, 1H ), 9. 56-9. 60 ( m, 1H) , 12.59 ( s, 1H) .

LC /M S : condit i on 1, re tent ion ti m e = 2. 94 m in LC /M S (E SI ) m /z; 370 [M +H ] LC /M S (E SI ) m /z; 368 [ M- H] H -N MR (D MS O- d ) δ: 1. 64-1. 79 (m, 1H) , 1. 82-2. 06 ( m, 2H) , 2. 13-2. 22 (m , 1H) , 2. 25 ( s, 3H ) , 3. 07 ( t, J = 12.2 H z, 1H ), 4. 22 (d, J = 13. 2 H z, 1H) , 4.43 (d, J = 12.9 H z, 1H) , 6.59 (s, 1H ), 6. 98 (d, J = 2. 6 H z, 1H ) , 7. 53 (d, J = 3. 3 H z, 1H ), 9. 57 (s, 1H ), 10. 46 (br s, 1H) , 12. 58 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 2. 90 m in LC /M S (E SI ) m /z; 383 [M +H ] LC /M S (E SI ) m /z; 381 [ M- H] H -N MR ( CD C l ) δ: 1. 26 ( t, J = 7.3 H z, 1H ) , 1.86- 2.01 (m , 2H ) , 2. 15-2. 27 ( m, 2H ), 2. 47 (t , J = 11.2 Hz, 1H) , 2. 98 ( d, J = 11.2 Hz, 1H ), 3. 11 (dt , J = 1 1.2, 1. 7 Hz, 1H ) , 3.40- 3.51 (m , 1H ), 3. 57 ( d, J = 13. 9 H z, 1H ), 3. 69 (d , J = 13. 9 H z, 1H ), 6. 66 ( dd, J = 3. 3, 2.0 H z, 1H ), 7.25- 7.28 (m , 1H ), 7. 49 (d, J = 8 .3 H z, 2H ), 7. 60 (d, J = 7 .9 Hz , 2H ), 9. 17 ( br s, 1H ), 9. 21 ( s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 0. 59 m in LC /M S (E SI ) m /z; 358 [M +H ] LC /M S (E SI ) m /z; 356 [ M- H] H -N MR ( CD C l ) δ: 1. 23-1. 32 (m , 1H ), 1.81- 1.98 (m , 2H) , 2.15- 2.27 ( m, 2H ), 2. 42 ( t , J = 1 1.2 Hz, 1H) , 3.0 1 ( d, J = 10.9 Hz, 1H) , 3.15 ( d, J = 10.6 Hz, 1H ), 3.45 ( td, J = 11.6, 3. 0 H z, 1H ), 3. 56 (d, J = 13.2 H z, 1H ), 3.71 (d, J = 13.2 Hz, 1H ), 6. 58-6. 62 ( m, 1H ), 7. 20-7. 24 (m , 1H ), 7. 48 ( d, J = 7 .9 H z, 2 H) , 7.56 (d, J = 7. 9 H z, 2H ), 9. 21 ( s, 2H ).

LC /M S : condit i on 1, re tent ion ti m e = 2. 49 m in LC /M S (E SI ) m /z; 401 [M +H ] LC /M S (E SI ) m /z; 399 [ M- H] H -N MR (C DC l ) δ: 1. 51 (s, 9H ), 1. 95-2. 20 (m , 4H ), 2. 85-3. 10 (m , 2H ), 3.2 9-3. 48 (m , 1H ), 4.15 -4.4 2 (m , 2H ) , 6. 71-6. 80 (m , 1H ) , 7. 27-7. 35 ( m, 1H ), 9. 23 ( s, 1H ), 9. 27 ( br s, 1H) .

LC /M S : condit i on 1, re tent ion ti m e = 3. 94 m in + t + LC /M S (E SI ) m /z; 343 [M - B u] LC /M S (E SI ) m /z; 341 [ M- H] TABLE 98 Ex D ata H -N MR (C D Cl ) δ: 1 .99 -2.10 (m , 2H ) , 2 .39 (d q, J = 11 .7, 3 .9 H z, 2H ), 2.6 5 (dt, J = 11.7 , 2 .4 Hz, 2H ), 3.0 9 (q, J = 9 .6 H z, 2H) , 3.1 1-3.2 9 (m , 3H ) , 6.8 5 ( d d, J = 2 .5, 0 .9 H z, 1H) , 7.3 1 ( dd , J = 3 .0, 2 5 0.9 H z, 1 H) , 9.11 (br s , 1H) , 9 .23 (s , 1H ).

LC /M S: co ndi tion 1, ret enti on time = 2.30 mi n LC /M S(ESI ) m /z; 3 25 [M+ H ] LC /M S(ESI ) m/z ; 32 3 [M -H ] H -N MR (C D Cl ) δ: 2 .00- 2 .15 ( m , 4H ), 3.0 1- 3.1 8 ( m, 2H ), 3 .32- 3 .45 (m, 1H ), 4.3 0-4.4 4 ( m , 2H ), 5.1 9 (s , 2H ), 6 .70-6 .76 (m , 1H) , 7.2 5-7.4 3 (m , 6H) , 9.1 8 (br s, 1 H) , 9.22 ( s, 1 H ).

LC /M S: co ndi tion 1, ret enti on time = 3.79 mi n LC /M S(ESI ) m /z; 3 77 [M+ H ] LC /M S(ESI ) m/z ; 37 5 [M -H ] H -N MR (C D O D ) δ : 2.0 5-2.1 5 (m , 4H) , 2.90 -3.13 (m, 2 H), 3 .38 -3 .50 (m, 1H ), 6.9 3 ( d , J = 3.3 Hz , 1 H), 7.40 ( d, J = 3. 3 H z, 1H) , 9. 31 (s , 1H ).

LC /M S: co ndi tion 1, ret enti on time = 0.44 mi n LC /M S(ESI ) m /z; 2 43 [M+ H ] LC /M S(ESI ) m/z ; 24 1 [M -H ] H -N MR (C D Cl ) δ: 1 .95- 2 .12 ( m , 2H ), 2.1 2- 2.3 1 ( m, 4H ), 2 .99- 3 .12 (m, 2H) , 3.1 7-3.3 1 (m , 1H) , 3 .61 (s , 2H ), 6 .85 (d, J = 2.4 Hz , 1H) , 7.2 3-7.3 5 (m , 2H ), 7 .74 (d , J = 7.8 Hz , 1H) , 8.52 (dd, J = 4 .5, 1 .2 2 8 H z, 1 H ), 8.62 (d, J = 2.1 Hz, 1 H) , 9.22 ( s, 1H) , 9.3 9 ( b r s, 1 H ) .

LC /M S: co ndi tion 3, ret enti on time = 0.52 mi n LC /M S(ESI ) m /z; 3 34 [M+ H ] LC /M S(ESI ) m/z ; 33 2 [M -H ] H -N MR (D MSO - d ) δ: 1. 64- 1 .82 (m, 1H ), 1. 86- 2 .04 (m, 3H) , 2.8 5-3.0 0 (m , 1H ), 3.3 0- 3.3 9 (m , 1H ), 3.45 - 3.60 ( m, 1H ), 3 .61 -3 .84 (m, 2H) , 3. 92-4. 05 (m , 1 H), 4.43 - 4.55 ( m , 1H ), 6 .82-6 .90 (m , 1 H ), 2 9 7.4 9-7.5 3 (m , 1H) , 9.5 3 (s , 1H ), 1 2.51 (br s , 1H ).

LC /M S: co ndi tion 3, ret enti on time = 1.62 mi n LC /M S(ESI ) m /z; 3 53 [M+ H ] LC /M S(ESI ) m/z ; 35 1 [M -H ] H -N MR (D MSO - d ) δ: 1. 70- 2 .10 (m, 4H ), 3. 09- 3 .26 (m, 2H) , 3.4 3-3.6 5 ( m, 1 H ), 4 .14-4 .50 (m , 2H ) , 6.8 5 (s, 1 H ) , 7 .49 (s, 1H) , 9.0 0 (br s , 1H ), 9.53 (s, 1 H ), 11. 34 (b r s, 1 H ), 12. 54 (b r s, 1 H ).

LC /M S: co ndi tion 3, ret enti on time = 1.40 mi n LC /M S(ESI ) m /z; 3 70 [M+ H ] LC /M S(ESI ) m/z ; 36 8 [M -H ] H -N MR (D MSO- d ) δ: 1.7 0-2.1 0 ( m, 4H ), 2 .27 (s , 3 H), 3. 10-3 .26 (m, 2H ), 3.4 3- 3.6 4 ( m, 1H ), 4 .15-4 .41 (m, 2 H) , 6 .63 (s , 1H ), 6 .83 -6 .89 (m, 1H ), 7.4 5-7. 52 ( m , 1H ), 9. 54 (s , 1H ), 1 0.48 (s, 1 H ), 12 .55 (b r s, 3 1 1H ).

LC /M S: co ndi tion 3, ret enti on time = 1.43 mi n LC /M S(ESI ) m /z; 3 83 [M+ H ] LC /M S(ESI ) m/z ; 38 1 [M -H ] TABLE 99 E x D ata H -N MR (D MS O- d ) δ: 1. 85-2. 08 (m, 4H) , 2. 13-2. 30 ( m, 2H) , 2. 90-3. 03 ( m, 2H ), 3. 11-3. 25 ( m, 1H ) , 3.55 (s, 2H ) , 6.81 (s, 1H ) , 32 7. 20-7. 40 ( m, 5H ), 7. 49 ( s, 1H ), 9. 52 ( s, 1H ), 12. 53 ( br s , 1H) .

LC /M S : condit i on 3, re tent ion ti m e = 1. 31 m in LC /M S (E SI ) m /z; 333 [M +H ] H -N MR (D MS O- d ) δ: 1. 87-2. 11 (m, 4H) , 2. 18-2. 31 ( m, 2H) , 2. 88-3. 02 ( m, 2H ), 3. 12-3. 26 ( m, 1H ) , 3.65 (s, 2H ) , 6.83 (s, 1H ) , 7. 49 ( m, 1H) , 7. 60 ( d, J = 8. 3 Hz, 2H ), 7. 71 (d, J = 8.3 H z, 2H ), 9.52 ( s, 1H) , 12.5 3 (b r s , 1H) .

LC /M S : condit i on 3, re tent ion ti m e = 1. 63 m in LC /M S (E SI ) m /z; 401 [M +H ] H -N MR (D MS O- d ) δ: 1. 85-2. 10 (m, 4H) , 2. 19-2. 33 ( m, 2H) , 2. 87-3. 00 (m , 2H ), 3.10- 3.26 (m , 1H) , 3. 65 (s, 2H ), 6. 82 (d, J = 3. 0 H z, 1H ), 7. 49 ( d, J = 3.0 H z, 1H ), 7. 58 ( d, J = 8.2 H z, 2H ), 7. 81 ( d, J 34 = 8. 2 H z, 2H ), 9. 52 ( s, 1H ), 12. 53 ( br s, 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 1. 23 m in LC /M S (E SI ) m /z; 358 [M +H ] LC /M S (E SI ) m /z; 356 [ M- H] H -N MR (D MS O- d ) δ: 1. 85-2. 10 (m, 4H) , 2. 18-2. 31 ( m, 2H) , 2. 87-2. 99 ( m, 2H ), 3. 13-3. 23 ( m, 1H ) , 3.62 (s, 2H ) , 6.83 (s, 1H ) , 7. 49 (s, 1H ), 7. 57 ( t, J = 7. 8 H z, 1H) , 7.67- 7.77 ( m, 2H ), 7. 94 (s, 1H ), 9. 52 ( s, 1H ), 12. 53 ( br s, 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 1. 24 m in LC /M S (E SI ) m /z; 358 [M +H ] LC /M S (E SI ) m /z; 356 [ M- H] H -N MR (D MS O -d ) δ: 1. 85-2. 05 (m , 4H ), 2.10- 2.30 ( m, 2H ), 2. 24 (s , 3H ), 2. 36 (s, 3H ), 2. 85-2. 99 (m , 2H ) , 3. 10-3. 27 (m , 1H ), 6.79 ( d, J = 3. 2 H z, 1H ), 7. 49 ( d, J = 3. 2 H z, 1H ), 9.52 (s, 1H ) , 12.53 (br s, 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 1. 07 m in LC /M S (E SI ) m /z; 352 [M +H ] LC /M S (E SI ) m /z; 350 [ M- H] H -N MR (D MS O- d ) δ: 1. 86-2. 08 (m, 4H) , 2. 16-2. 29 ( m, 2H) , 2. 88-3. 00 (m , 2H ), 3.10- 3.25 (m , 1H) , 3. 58 (s, 2H ), 6. 82 (d, J = 3. 0 H z, 1H ), 7. 34 (d, J = 8. 4 H z, 2H ), 7.46-7. 55 (m , 3H) , 9.53 (s , 1H ), 37 12. 54 ( br s, 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 1. 69 m in LC /M S (E SI ) m /z; 417 [M +H ] LC /M S (E SI ) m /z; 415 [ M- H] H -N MR (D MS O- d ) δ: 1. 87-2. 06 (m, 4H) , 2. 16-2. 30 ( m, 2H) , 2. 90-3. 03 (m , 2H) , 3.12- 3.25 ( m, 1H ), 3.6 3 (s, 2H ), 6. 80-6. 85 (m , 1H ), 7.49- 7.53 (m , 1H ), 7. 55 (d, J = 7 .8 H z, 2H ), 7. 70 (d, J = 7 .8 Hz , 38 2H ), 9. 53 ( s, 1H ), 12. 54 ( br s, 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 1. 78 m in LC /M S (E SI ) m /z; 433 [M +H ] LC /M S (E SI ) m /z; 431 [ M- H] TABLE 100 E x D ata H -N MR ( DM S O- d ) δ: 1 .85- 2.15 (m , 4H ) , 2.20- 2.38 (m, 2H ) , 2. 88-3. 08 (m , 2H) , 3. 12-3. 27 (m , 1H ), 3.66 ( s, 2H) , 6.82 ( d, J = 3.0 H z, 1H ), 7. 49 ( s, 1H ), 7. 52-7 .80 (m, 4H ) , 9.52 (s, 1H) , 12.53 (br s , 39 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 1. 60 m in LC /M S (E SI ) m /z; 401 [ M+H ] LC /M S (E SI ) m / z; 399 [ M- H] H -N MR ( D MS O-d ) δ: 1. 95-2. 09 ( m, 4H ), 2. 27-2. 33 (m , 2H ), 2.96 ( d, J = 11.4 H z, 2H) , 3 .15- 3.20 (m , 1H ), 3. 69 ( s, 2H ), 6.82 (dd, J = 3. 2, 1. 4 H z, 1H ), 7. 50 (t , J = 2.9 H z, 1 H) , 7.72 ( d, J = 4.2 H z, 2H ) , 40 7. 84 ( d, J = 9. 9 H z, 1 H) , 9.53 (s, 1H ) , 12.54 (br s, 1H ) .

LC /M S : condi ti on 3, r etent ion t im e = 1. 28 m in LC /M S (E SI ) m /z; 376 [ M+H ] LC /M S (E SI ) m / z; 374 [ M- H] H -N MR ( DM S O- d ) δ: 1 .85- 2.05 (m , 4H ) , 2.14- 2.30 (m, 2H ) , 2. 86-3. 00 (m , 2H) , 3 .10- 3.25 ( m, 1H ), 3.53 (s, 2H ), 6.79 -6.8 6 (m , 1H ), 7. 33 ( d, J = 8.3 Hz, 2H ) , 7.44- 7.52 (m , 1H ), 7. 53 ( d, J = 8.3 H z, 2H ), 9. 52 ( s, 1H ), 12. 53 ( br s, 1H) .

LC /M S : condi ti on 3, r etent ion t im e = 1. 58 m in LC /M S (E SI ) m /z; 411, 413 [ M+H ] H -N MR ( DM S O- d ) δ: 2 .15- 2.37 (m , 4H ) , 3.16- 3.30 (m, 3H ) , 3. 36-3. 50 ( m, 3H) , 3.50- 3.73 ( m, 1H ), 3.79- 3.82 (m , 2H ), 7. 07 (br s , 1H ), 7. 53-7. 62 (m , 3H ), 7.70- 7.79 (m , 2H ) , 9. 57 ( s, 1H ), 9.75- 9.98 42 ( br s, 1H) , 12.6 1 (b r s , 1H) .

LC /M S : condi ti on 3, r etent ion t im e = 1. 79 m in LC /M S (E SI ) m /z; 415 [ M+H ] LC /M S (E SI ) m / z; 413 [ M- H] H -N MR (D MS O- d ) δ: 1. 94-2. 06 ( m, 4H) , 2.20 ( td, J = 10.8, 3. 3 Hz, 2H ), 2.94 (d, J = 11. 7 H z, 2H ), 3. 18 (s eptet , J = 5. 2 H z, 1H ), 3.54 ( s, 2H ), 6. 82 (d, J = 3. 3 H z, 1H ), 7.16 (t t, J = 9. 2, 2. 5 H z, 2H ), 7.40 ( dd, J = 8.4, 5.7 H z, 2H ) , 7. 50 (d, J = 3. 3 H z, 1H ), 9. 52 ( s, 1H) , 12. 53 ( br s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 1. 49 m in LC /M S (E SI ) m /z; 351 [ M+H ] LC /M S (E SI ) m / z; 349 [ M- H] H -N MR ( DM S O- d ) δ: 1 .86- 2.08 (m , 4H ) , 2.20- 2.35 (m, 2H ) , 2. 92-3. 06 (m , 2H) , 3. 10-3. 25 (m , 1H ), 3.84 ( s, 2H) , 6.82 ( d, J = 3.3 H z, 1 H) , 7. 49 ( d, J = 3. 3 H z, 1H) , 7 .80 ( s, 1H ), 9.03 ( s, 1H ), 9.52 44 ( s, 1H) , 12. 53 ( br s , 1H) .

LC /M S : condi ti on 3, r etent ion t im e = 0. 62 m in + + - LC /M S (E SI ) m /z; 340 [ M+H ] LC /M S (E SI ) m / z; 338 [ M- H] H -N MR ( DM S O- d ) δ: 1 .73- 1.88 (m , 2H ) , 1.88- 2.12 (m, 4H ) , 2. 14-2. 32 (m, 2H) , 2. 33-2. 50 ( m, 2 H) , 2.59- 2.71 (m , 2H ) , 2.98- 3.13 ( m, 2H) , 3.14- 3.25 ( m, 1H ), 6.82 (s, 1H ), 7.10- 7.36 (m, 5H ), 7.49 45 ( s, 1H) , 9.5 2 (s , 1H) , 12.53 (br s , 1H) .

LC /M S : condi ti on 3, r etent ion t im e = 1. 55 m in LC /M S (E SI ) m /z; 361 [ M+H ] LC /M S (E SI ) m / z; 359 [ M- H] TABLE 101 E x D ata H -N MR (D MS O -d ) δ: 1.91- 2.05 ( m, 4H) , 2. 16-2. 23 (m , 2H ), 2.94 (d, J = 11. 4 H z, 2H ) , 3. 14-3. 21 (m , 1H ), 3.50 ( s, 2H) , 3.83 ( s, 3H ), 6.82 ( t, J = 2. 4 H z, 1H) , 7.12- 7.20 (m , 3H ) , 7. 50 ( t, J = 2. 7 H z, 1H ), 9.53 ( s, 1H) , 12.5 4 (b r s , 1H) .

LC /M S : condit i on 3, re tent ion ti m e = 1. 39 m in LC /M S (E SI ) m /z; 381 [M +H ] H -N MR (D MS O- d ) δ: 1. 85-2. 09 (m, 4H) , 2. 22-2. 39 ( m, 2H) , 2. 88-3. 03 (m , 2H ), 3.12- 3.25 (m , 1H) , 3. 78 (s, 2H ), 6. 84 (d, J = 2. 8 H z, 1H ), 7.49 ( d, J = 2. 8 Hz, 1H ), 8. 00 (s, 1H) , 8. 07 (s, 2H ), 9.52 ( s, 47 1H ), 12. 55 ( br s, 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 1. 84 m in LC /M S (E SI ) m /z; 469 [M +H ] LC /M S (E SI ) m /z; 467 [ M- H] H -N MR (D MS O- d ) δ: 1. 88-2. 13 (m, 4H) , 2. 32-2. 46 ( m, 2H) , 2. 97-3. 10 (m , 2H ), 3.14- 3.27 (m , 1H) , 3. 91 (s, 2H ), 6. 85 (d, J = 3. 0 H z, 1H ), 7. 51 ( d, J = 3.0 H z, 1H ), 7. 67 ( d, J = 3.3 H z, 1H ), 7. 72 ( d, J 48 = 3. 3 H z, 1H ), 9. 52 ( s, 1H ), 12. 55 ( br s, 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 0. 91 m in LC /M S (E SI ) m /z; 340 [M +H ] LC /M S (E SI ) m /z; 338 [ M- H] H -N MR (D MS O- d ) δ: 1. 87-2. 07 (m, 4H) , 2. 18-2. 34 ( m, 2H) , 2. 94-3. 08 (m , 2H ), 3.12- 3.34 (m , 1H) , 3. 71 (s, 2H ), 6. 82 (d, J = 3. 3 H z, 1H ), 6. 87 ( d, J = 3.3 H z, 1H ), 6. 96 ( d, J = 3.6 H z, 1H ), 7. 50 ( d, J 49 = 3. 6 H z, 1H ), 9. 52 ( s, 1H ), 12. 55 ( br s, 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 1. 49 m in LC /M S (E SI ) m /z; 373, 3 75 [ M+H ] LC /M S (E SI ) m /z; 371, 373 [ M- H] H -N MR (D MS O- d ) δ: 0. 78-0. 98 (m, 2H) , 1. 12-1. 32 ( m, 3H) , 1. 59-1. 72 (m, 2H ), 1. 72-1. 85 (m , 2H ), 1.85- 2.04 (m , 4H ), 2.04- 2.23 ( m, 3H ) , 2.67- 2.78 ( m, 2H) , 2. 88-3. 05 ( m, 3H) , 3. 08-3. 21 (m , 1H ), 50 6. 79 ( s, 1H ), 7. 49 ( s, 1H ), 9.5 2 (s , 1H) , 12.52 (br s , 1H) .

LC /M S : condit i on 3, re tent ion ti m e = 1. 51 m in LC /M S (E SI ) m /z; 339 [M +H ] LC /M S (E SI ) m /z; 337 [ M- H] H -N MR (D MS O- d ) δ: 1. 32-1. 70 (m, 6H) , 1. 77-2. 05 ( m, 6H) , 2. 06-2. 30 ( m, 2H ), 3. 04-3. 23 ( m, 3H ), 6. 80 ( d, J = 3. 0 H z, 1H ) , 7.49 ( s, 1H) , 9.52 (s , 1H) , 12.53 (br s, 1H) .

LC /M S : condit i on 3, re tent ion ti m e = 1. 18 m in LC /M S (E SI ) m /z; 311 [M +H ] H -N MR (D MS O- d ) δ: 1. 86-2. 10 (m, 4H) , 2. 23-2. 35 ( m, 2H) , 2. 90-3. 03 (m , 2H ), 3.14- 3.27 (m , 1H) , 3. 71 (s, 2H ), 6. 83 (d, J = 3. 3 H z, 1H ), 7. 49 ( d, J = 3.3 H z, 1H ), 7. 89 ( d, J = 8.1 H z, 1H ), 8. 07 ( d, J 52 = 9. 3 H z, 1H ), 8. 75 ( s, 1H ), 9. 52 ( s, 1H ), 12. 53 ( br s, 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 1. 40 m in LC /M S (E SI ) m /z; 402 [M +H ] LC /M S (E SI ) m /z; 400 [ M- H] TABLE 102 E x D ata H -N MR (D MS O- d ) δ: 1. 90-1. 97 (m, 4H) , 2. 26-2. 34 ( m, 2H) , 2. 93-2. 97 (m, 2H ), 3. 13 (qui nt , J = 6. 2 Hz, 1H ), 3. 72 (s, 2H ), 6.80 ( dd, J = 2.9 H z, 1. 7 Hz, 1H ), 7. 47 (t , J = 2.9 H z, 1H) , 7. 81 (s, 1H) , 7. 84 ( s, 1H ), 9. 51 ( s, 1H ), 12. 51 ( br s , 1H) .

LC /M S : condit i on 3, re tent ion ti m e = 1. 26 m in LC /M S (E SI ) m /z; 394 [M +H ] H -N MR (D MS O -d ) δ: 1.95- 2.02 ( m, 4H) , 2. 18-2. 24 (m , 2H ), 2.94 (d, J = 11.4 H z, 2H) , 3. 55 ( s, 2H ), 6. 79 ( d, J = 3. 0 H z, 1H ) , 7.40 (s, 4H ) , 7. 48 ( d, J = 3. 0 H z, 1H ) , 9.48 (s, 1H ) .

LC /M S : condit i on 3, re tent ion ti m e = 1. 75 m in LC /M S (E SI ) m /z; 367, 3 69 [ M+H ] LC /M S (E SI ) m /z; 365, 367 [ M- H] H -N MR (D MS O -d ) δ: 1.95- 2.03 ( m, 4H) , 2. 19-2. 27 (m , 2H ), 2.95 (d, J = 12.0 H z, 2H ) , 3.58 (s, 2H ) , 6.80 (d, J = 2.7 H z, 1H) , 7.05- 7.22 55 ( m, 3H ), 7. 35-7. 42 ( m, 1H ), 7.48 (d, J = 3.3 H z, 1 H) , 9.49( s, 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 1. 61 m in LC /M S (E SI ) m /z; 351 [M +H ] H -N MR (D MS O- d ) δ: 1. 20-1. 52 (m, 4H) , 1. 86-2. 10 ( m, 8H) , 2. 16-2. 41 ( m, 3H ), 2.63- 2.80 (m , 1H ), 2. 88-3. 24 (m , 3H) , 6. 84 ( br s, 1H ), 7. 46-7. 53 ( m, 1H ), 9. 52 ( s, 1H ), 12. 53 ( br s, 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 1. 57 m in LC /M S (E SI ) m /z; 393 [M +H ] LC /M S (E SI ) m /z; 391 [ M- H] H -N MR (D MS O- d ) δ: 1. 40-1. 66 (m, 4H) , 1. 66-1. 85 ( m, 2H) , 1. 92-2. 18 (m, 8H ), 2. 34-2. 40 (m , 1H ), 2.65- 2.77 (m , 1H ), 3.08- 3.28 ( m, 3H) , 6. 78-6. 84 (m , 1H ) , 7. 45-7. 56 (m , 1H ), 9. 52 (s, 1H ), 1 2.53 56b ( br s , 1H) .

LC /M S : condit i on 3, re tent ion ti m e = 1. 53 m in LC /M S (E SI ) m /z; 393 [M +H ] LC /M S (E SI ) m /z; 391 [ M- H] H -N MR (D MS O- d ) δ: 1. 83-2. 10 (m, 4H) , 3. 06-3. 22 ( m, 2H) , 3. 43-3. 60 ( m, 1H ), 4. 20-4. 35 ( m, 2H ), 6. 86 ( d, J = 3. 3 H z, 1H ) , 7.26 ( d, J = 8.1 H z, 1H ), 7.42- 7.53 ( m, 2H ), 7.79 (d, J = 8.1 H z, 1H ), 7.97 57 ( s, 1H) , 8.94 (s , 1H) , 9.54 (s, 1H) , 12.57 (br s, 1H ) .

LC /M S : condit i on 3, re tent ion ti m e = 2. 14 m in LC /M S (E SI ) m /z; 430 [M +H ] LC /M S (E SI ) m /z; 428 [ M- H] H -N MR (D MS O -d ) δ: 1. 93-2. 07 ( m, 4H) , 3. 17 ( br s, 1H ), 3.56- 3.62 ( m, 2H ), 4.5 8 (br s, 1H ), 6. 86 ( d, J = 3. 0 H z, 1H) , 7.50 (d, J = 3.0 H z, 1H ), 7. 68 ( d, J = 8. 1 H z, 2H ), 7.85 (d, J = 8. 4 Hz, 2H ) , 9.50 (s, 58 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 2. 13 m in LC /M S (E SI ) m /z; 415 [M +H ] LC /M S (E SI ) m /z; 413 [ M- H] TABLE 103 Ex D ata H -N MR (C D Cl ) δ: 1 .20-1 .42 (m, 4 H ), 1.4 8 (s , 9H) , 1 .92 -2.30 (m, 5H ), 3 .10-3 .25 (m , 1H) , 3 .63 ( br s , 1H) , 4. 47 ( b r s, 1H ) , 6.7 9 ( dd , J = 3.3 , 1.8 H z, 1H ), 7.29 (dd , J = 3. 3, 1. 8 H z, 1H ), 9.2 2 (s , 1H ).

LC /M S: co ndi tion 1, ret enti on time = 3.74 mi n LC /M S(ESI ) m /z; 3 57 [M+ H ] LC /M S(ESI ) m/z ; 35 5 [M -H ] H -N MR (D MSO - d ) δ: 1 .18 (d, J = 6.6 H z, 1H) , 1.3 8-1. 57 (m , 2H) , 1.7 1-1.9 0 (m , 2H ), 1.9 1- 2.1 0 (m , 4H ), 3.05 - 3.20 ( m, 1H ), 3 .37 -3 .54 (m, 1H) , 5.0 3 ( s , 2H ), 6 .81 (d , J = 3 .3 H z , 1H) , 7 .26-7 .42 (m , 5H) , 7.4 8 (d, J = 3.3 H z, 1H) , 9.5 1 (s , 1H ), 1 2.51 (br s , 1H ).

LC /M S: co ndi tion 3, ret enti on time = 2.10 mi n LC /M S(ESI ) m /z; 3 91 [M+ H ] LC /M S: co ndi tion 3, ret enti on time = 0.50 mi n LC /M S(ESI ) m /z; 2 57 [M+ H ] H -N MR (C D Cl ) δ: 1 .15- 1 .35 ( m , 2H ), 1.7 0- 1.8 5 ( m, 1H ), 1 .86- 2 .07 (m, 4H ), 2 .08-2 .23 (m , 2 H ), 3 .09-3 .25 ( m , 1H ), 3 .30 ( d , J = 6 .3 H z, 2H ), 3.3 8 (s , 3H ), 6.73 -6.83 ( m , 1H ), 7 .21 -7 .33 ( m , 1 H ), 9 .02 (br s, 6 2 1H ), 9 .21 (s , 1H ).

LC /M S: co ndi tion 1, ret enti on time = 3.57 mi n LC /M S(ESI ) m /z; 2 86 [M+ H ] LC /M S(ESI ) m/z ; 28 4 [M -H ] H -N MR (C D Cl ) δ : 1.46 , (m, 2 H ) , 1.95 (m , 2H) , 2 .24 ( m , 4H ), 3 .18 (tt, J = 12 .0, 3. 3H z, 1 H), 3 .34 (tt , J = 10.8 , 3.9 H z , 1H ), 3.4 3 ( s, 3H ), 6 .79 (m , 1H ), , 7.30 ( m, 1H ), 9.2 2 ( s, 1H ) , 9.3 1 ( b r s, 1 H ).

LC /M S: co ndi tion 1, ret enti on time = 3.13 mi n LC /M S(ESI ) m /z; 2 72 [M+ H ] LC /M S(ESI ) m/z ; 27 0 [M -H ] H -N MR (CD C l ) δ: 1 .83-2 .43 (m, 8H) , 3.27 -3.45 ( m , 1 H ), 6.8 1 (dd, J = 3.3, 2.1 Hz , 1H ) , 7 .28 -7.39 (m, 1 H ), 9.24 (s, 1 H ), 9.2 5 (br s , 1H ). 6 4 LC /M S: co ndi tion 1, ret enti on time = 3.59 mi n LC /M S(ESI ) m /z; 2 78 [M+ H ] LC /M S(ESI ) m/z ; 27 6 [M -H ] H -N MR (C D Cl ) δ : 1.2 3-1. 87 (m , 7H ) , 2 .46 (m , 2H ), 2.57 ( s, 1 H), 3.2 2 (m, 1H) , 6. 80 ( m, 1H ), 7.2 9 (t, J = 3 .3 H z, 1H ), 9.1 7 (br s, 1H) , 9.2 2 (s , 1H ).

LC /M S: co ndi tion 1, ret enti on time = 3.89 mi n LC /M S(ESI ) m /z; 2 54 [M+ H ] LC /M S(ESI ) m/z ; 25 2 [M -H ] H -N MR (C DC l ) δ: 1.6 7-1.7 5 (m, 6H) , 1.9 2 (m, 2H) , 2.0 6-2.1 4 (m, 4H ), 3 .40 (t t, J = 9 .6, 4.8 Hz , 1H ), 6.80 (m, 1H ) , 7.2 7 (t, J = 2.7 H z, 1H ), 9 .03 (b r s, 1H ), 9.2 1 (s, 1H ).

LC /M S: co ndi tion 1, ret enti on time = 3.94 mi n LC /M S(ESI ) m /z; 2 56 [M+ H ] LC /M S(ESI ) m/z ; 25 4 [M -H ] TABLE 104 E x D ata H -N MR (C DC l ) δ: 2.06 -2.2 7 ( m, 2H ), 2.45- 2.72 (m , 4H) , 4. 05 ( quin ｔ , 8.4H z, 1H) , 6. 80 (dd, J = 3.3, 2.1, 1H ), 7.29 ( t, J = 2.7H z, 1H ) , 9. 17 ( br s, 1H ), 9. 22 ( s, 1H) .

LC /M S : condit i on 1, re tent ion ti m e = 3. 34 m in LC /M S (E SI ) m /z; 214 [M +H ] LC /M S (E SI ) m /z; 212 [ M- H] H -N MR (C DC l ) δ: 1. 60-2. 08 (m, 8H ), 3. 71 ( qui nｔ , J = 9. 0Hz, 1H) , 7. 02 ( dd, J = 3. 3, 2.1 , 1H) , 7. 34 ( dd, J = 3. 6, 2.4H z, 1H ) , 8.88 (s , 1H ), 10. 05 ( br s, 1H ).

H -N MR (D MS O- d ) δ: 1. 50-1. 70 (m, 2H) , 1. 71-1. 92 ( m, 2H) , 1. 93-2. 18 (m, 4H ), 2. 30-2. 67 (m , 1H ), 3.15- 3.38 (m , 1H ), 6.87- 7.00 ( m, 1H ), 7. 40-7. 55 ( m, 1H ), 9.52 (s, 1H ), 12. 52 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 97 m in LC /M S (E SI ) m /z; 310 [M +H ] LC /M S (E SI ) m /z; 308 [ M- H] H -N MR (D MS O- d ) δ: 1. 49-1. 70 (m, 2H) , 1. 72-1. 93 ( m, 2H) , 1. 95-2. 15 (m , 4H) , 2.36- 2.66 (m , 1H ), 3. 14-3. 39 (m , 1H ), 6.93 (dd, J = 3. 3, 1.8 Hz, 1H) , 7.42- 7.55 (m , 1H ), 9.52 (s , 1H) , 12.52 (br s, 1H ) .

LC /M S : condit i on 1, re tent ion ti m e = 3. 95 m in LC /M S (E SI ) m /z; 310 [M +H ] LC /M S (E SI ) m /z; 308 [ M- H] H -N MR (D MS O -d ) δ: 1. 10-1. 43 (m , 2H ), 1.49- 2.17 ( m, 7H ), 2. 36 (s , 3H ), 2. 87 (d, J = 6.6 H z, 2H ), 3. 05-3. 22 ( m, 1H ), 6 .73-6 .90 (m, 1H ) , 7. 40-7. 59 ( m, 1H ), 9. 50 ( s, 1H ), 12. 50 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 88 m in LC /M S (E SI ) m /z; 330 [M +H ] LC /M S (E SI ) m /z; 328 [ M- H] H -N MR (C DC l ) δ: 1. 17-1. 40 (m , 2H ), 1.71- 2.28 (m , 7H ), 2.10 (s , 3H ), 3.10- 3.27 ( m, 1H ), 4 .00 (d , J = 6. 6 Hz, 2H ), 6.79 ( dd, J = 3. 3, 2. 1 H z, 1H ), 7. 21-7. 35 ( m, 1H ), 9. 12 ( br s, 1H ), 9. 22 ( s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 55 m in LC /M S (E SI ) m /z; 314 [M +H ] LC /M S (E SI ) m /z; 312 [ M- H] H -N MR ( CD C l ) δ: 1. 20-1. 50 (m , 2H ), 1.64- 2.40 (m , 7H) , 3.05- 3.60 ( m, 1H ) , 4.20- 4.50 ( m, 2H) , 6. 70-7. 00 ( m, 1H) , 7. 20-7. 40 (m , 1H ), 9. 10 ( br s, 1H ), 9. 22 ( s, 1H) .

LC /M S : condit i on 1, re tent ion ti m e = 3. 63 m in LC /M S (E SI ) m /z; 274 [M +H ] LC /M S (E SI ) m /z; 272 [ M- H] H -N MR ( CD C l ) δ: 1. 20-1. 45 (m , 2H ), 1.75- 2.28 (m , 7H) , 3.07- 3.23 ( m, 1H ), 3.41 (d, J = 6. 0 H z, 2H) , 6.72-6. 84 ( m, 1H ), 7. 24- 7.35 (m , 1H ), 9. 02 ( br s, 1H ), 9. 22 ( s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 97 m in LC /M S (E SI ) m /z; 334, 3 36 [ M+H ] LC /M S (E SI ) m /z; 332, 334 [ M- H] TABLE 105 E x D ata H -N MR ( CD C l ) δ: 1. 23-1. 44 (m , 2H ), 1.76- 2.27 (m , 7H) , 3.09- 3.25 ( m, 1H ), 3.51 (d, J = 6.6 Hz, 2H ), 6. 79 ( dd, J = 3.3, 2.1 H z, 1H ), 75 7. 20-7. 33 ( m, 1H ), 9. 03 ( br s, 1H ), 9. 22 ( s, 1H) .

LC /M S : condit i on 2, re tent ion ti m e = 1. 75 m in LC /M S (E SI ) m /z; 290, 2 92 [ M+H ] H -N MR ( CD C l ) δ: 1. 15-1. 31 (m , 2H ), 1.32- 1.42 (m , 1H) , 1.50- 1.73 ( m, 1H) , 1. 85-2. 03 (m , 2 H) , 2. 04-2. 25 (m , 4H ), 2. 55 (dd, J = 8. 3, 6.6 H z, 2H ), 3.06- 3.25 (m , 1H ), 6. 72-6. 85 (m , 1H) , 7. 20-7. 36 ( m, 1H ) , 9. 00 ( br s, 1H ), 9. 21 ( s, 1H) .

LC /M S : condit i on 1, re tent ion ti m e = 3. 84 m in LC /M S (E SI ) m /z; 288 [M +H ] LC /M S (E SI ) m /z; 286 [ M- H] H -N MR ( CD C l ) δ: 1. 32-1. 50 (m , 2H ), 1.90- 2.09 (m , 2H) , 2.01- 2.36 ( m, 5H ), 2.97 (s , 3H) , 3.04 ( d, J = 5.4 H z, 2H ), 3. 10-3. 29 ( m, 1H ) , 6. 78 (dd, J = 2.1, 3. 3 H z, 1H ), 7. 29 (t , J = 3.0 H z, 1H ), 9.00 ( br s , 77 1H ), 9. 21 ( s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 2. 87 m in LC /M S (E SI ) m /z; 334 [M +H ] LC /M S (E SI ) m /z; 332 [ M- H] H -N MR ( CD C l ) δ: 1. 41-1. 69 (m , 2H ), 1.89- 2.10 (m , 2H) , 2.16- 2.32 ( m, 4H ) , 2.36- 2.54 ( m, 1H) , 3. 09-3. 27 ( m, 1H) , 6. 70-6. 80 (m , 1H ), 7. 27-7. 35 (m , 1H ) , 9. 03 (br s, 1H) , 9. 22 ( s, 1 H) , 9. 74 (d, J = 1. 2 Hz , 78 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 13 m in LC /M S (E SI ) m /z; 270 [M +H ] LC /M S (E SI ) m /z; 268 [ M- H] H -N MR ( CD C l ) δ: 1. 35-1. 60 (m , 2H ), 1.80- 2.40 (m , 7H) , 3.10- 3.60 ( m, 1H ) , 5.40- 5.90 ( m, 1H) , 6. 72-6. 85 ( m, 1H) , 7. 20-7. 40 (m , 1H ), 9. 02 ( br s, 1H ), 9. 22 ( s, 1H) .

LC /M S : condit i on 1, re tent ion ti m e = 3. 74 m in LC /M S (E SI ) m /z; 292 [M +H ] LC /M S (E SI ) m /z; 290 [ M- H] H -N MR ( D MS O- d ) δ: 1. 60 ( dq, J = 12.2, 2. 3 H z, 2H ), 1. 78 ( dq, J = 12. 6, 2. 3 H z, 2H ), 1. 97-2. 10 (m , 4H ), 2.26- 2.37 (m , 1H ), 2.43- 2.47 ( m, 1H) , 3. 17 (t t , J = 11. 6, 3.3 H z, 1H ), 6.86 ( d, J = 3. 3 H z, 1H) , 80 7. 49 ( d, J = 3. 0 H z, 1H ) , 9.52 (s, 1H ) , 12.53 (br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 2. 70 m in LC /M S (E SI ) m /z; 286 [M +H ] LC /M S (E SI ) m /z; 284 [ M- H] H -N MR (C D O D ) δ: 1. 54 (q, J = 11. 2 H z, 2 H) , 1. 91 (dq, J = 12.2, 4. 0 Hz, 2H) , 2. 05-2. 18 (m , 4H ), 3.17 (dt , J = 12.9, 3.3 H z, 1H ), 3. 67-3. 78 ( m, 1H ) , 6. 82 ( d, J = 3. 0 H z, 1H) , 7. 40 ( d, J = 3. 3 Hz, 1H) , 81 9. 30 ( s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 1. 79 m in LC /M S (E SI ) m /z; 258 [M +H ] LC /M S (E SI ) m /z; 256 [ M- H] TABLE 106 E x D ata H -N MR ( CD Cl ) δ: 2. 38-2. 47 (m , 4H) , 2.53- 2.65 (m , 2H ) , 2. 71 ( dt, J = 14.5, 5. 0 H z, 2H ) , 3. 65-3. 77 ( m, 1H) , 6.80 ( dd, J = 3.6, 2. 0 H z, 1H ), 7. 33 ( t, J = 3. 0 H z, 1H ), 9. 26 ( s, 2H ).

LC /M S : condit i on 1, re tent ion ti m e = 2. 55 m in LC /M S (E SI ) m /z; 256 [M +H ] LC /M S (E SI ) m /z; 254 [ M- H] H -N MR ( CD OD ) δ: 1.79 (m , 4 H) , 1.97 ( m, 2H ), 2. 34 (m , 2H ), 3.26 ( m, 1H ), 4. 10 ( br s, 1H) , 6.96 (d, J = 3. 3H z, 1H ), 7. 37 ( d, J = 3.0 Hz , 1H ), 7. 89 ( s, 1H ), 9. 28 ( s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 2. 67 m in LC /M S (E SI ) m /z; 258 [M +H ] LC /M S (E SI ) m /z; 256 [ M- H] H -N MR ( CD Cl ) δ: 1.97- 2.09 (m , 4H ), 3. 02 (br s, 2H ), 3.1 9-3. 26 (m , 1H ), 4. 37 (br s, 2H) , 5.18 ( s, 2H ), 6.61 (dd, J = 3.2, 2. 3 H z, 1H) , 7. 09 (t , J = 3.0 H z, 1H ) , 7. 28-7. 41 ( m, 5H ), 8.11 (s, 1H ), 8. 50 (s , 1H ), 8. 89 ( br s, 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 2. 05 m in LC /M S (E SI ) m /z; 376 [M +H ] H -N MR (D MS O -d ) δ: 1. 64-1. 92 ( m, 4H) , 3. 01 ( br s, 2H ), 3.20- 3.30 ( m, 1H ), 4.07- 4.20 ( m, 2H ), 5.12 ( s, 2H) , 6. 63 ( br s, 1H ), 7.14- 7.20 ( m, 1H ), 7. 29-7. 43 (m , 5H ), 8. 63 (s , 1H) , 1 2.05 (br s, 1H ), 13. 14 ( br 85 s, 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 2. 20 m in LC /M S (E SI ) m /z; 408 [M +H ] LC /M S (E SI ) m /z; 406 [ M- H] H -N MR (D MS O- d ) δ: 1. 62-1. 76 (m, 2H) , 1. 90-2. 09 ( m, 2H) , 2. 13-2. 28 (m , 2H ) , 2. 85-3. 05 (m , 3H ) , 3. 63 (s , 2H ), 6. 56 (br s, 1H) , 7. 14-7. 21 ( m, 1H ) , 7. 69 ( d, J = 8. 3 H z, 2H) , 7. 71 ( d, J = 8. 3 Hz, 2H) , 86 8. 64 ( s, 1H ), 12. 05 ( br s, 1H ), 13. 14 ( br s , 1H) .

LC /M S : condit i on 3, re tent ion ti m e = 1. 64 m in LC /M S (E SI ) m /z; 432 [M +H ] LC /M S (E SI ) m /z; 430 [ M- H] LC /M S : condit i on 3, re tent ion ti m e = 2. 01 m in 87 LC /M S (E SI ) m /z; 349 [M +H ] LC /M S (E SI ) m /z; 347 [ M- H] H -N MR ( CD C l ) δ: 1. 07-1. 33 (m , 2H ), 1.45- 1.73 (m , 1H) , 1.80- 2.28 ( m, 6H ), 2.40 (d, J = 7. 1 H z, 2H) , 2.90-3. 28 ( m, 9H ), 6. 71- 6.84 (m , 1H ), 7. 20-7. 40 ( m, 1H ), 9. 02 ( br s, 1H ), 9. 22 ( s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 1. 84 m in LC /M S (E SI ) m /z; 389 [M +H ] LC /M S (E SI ) m /z; 387 [ M- H] H -N MR ( CD Cl ) δ: 1. 04-1 .24 ( m, 2H) , 1.60- 2.40 (m, 15H ), 2.55- 2.77 ( m, 3H ) , 3.05- 3.25 ( m, 1H) , 6. 71-6. 84 ( m, 1H) , 7. 20-7. 36 (m , 1H ), 8. 99 ( br s, 1H ), 9. 21 ( s, 1H) .

LC /M S : condit i on 1, re tent ion ti m e = 0. 39 m in LC /M S (E SI ) m /z; 364 [M +H ] LC /M S (E SI ) m /z; 362 [ M- H] TABLE 107 E x D ata H -N MR ( CD C l ) δ: 1. 21-1. 32 (m , 2H ), 1.40- 2.27 (m , 8H) , 2.50- 2.75 ( m, 4H ), 2 .97 (t , J = 6.3 H z, 2H ), 3. 10-3. 25 ( m, 1H) , 6.71- 6.87 (m , 1H ), 7. 20-7. 35 ( m, 1H ), 9. 00 ( br s, 1H ), 9. 21 ( s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 0. 37 m in LC /M S (E SI ) m /z; 324 [M +H ] LC /M S (E SI ) m /z; 322 [ M- H] H -N MR ( CD C l ) δ: 1. 05-1. 31 (m , 2H ), 1.61- 1.80 (m , 1H) , 1.81- 1.99 ( m, 2H ), 2.00- 2.20 (m , 4H ), 2. 24 ( d, J = 7.1 H z, 2H ), 2. 39- 2.53 (m , 4H ), 3.1 0-3. 25 (m , 1H ), 3.65 -3.8 1 (m , 4H ) , 6. 71-6. 85 (m , 1H ) , 91 7. 20-7. 35 ( m, 1H ), 9. 00 ( br s, 1H ), 9. 21 ( s, 1H) .

LC /M S : condit i on 1, re tent ion ti m e = 0. 37 m in LC /M S (E SI ) m /z; 341 [M +H ] LC /M S (E SI ) m /z; 339 [ M- H] H -N MR (D MS O- d ) δ: 1. 15-1. 40 (m, 2H) , 1. 55-1. 90 ( m, 3H) , 1. 92-2. 12 ( m, 4H ) , 2.99- 3.09 (m , 2H ), 3. 00-3. 26 (m, 1H) , 6.69 (d , J = 8. 9 H z, 2H ), 6.81 (d, J = 3. 3 H z, 2H ), 7. 45 ( d, J = 8. 6 H z, 2H ), 7.50 92 ( d, J = 3. 3 H z, 1H ), 9.52 (s, 1H ), 12 .54 (br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 95 m in LC /M S (E SI ) m /z; 372 [M +H ] LC /M S (E SI ) m /z; 370 [ M- H] H -N MR ( CD C l ) δ: 1. 10-1. 31 (m , 2H ), 1.50- 1.77 (m , 1H) , 1.82- 2.20 ( m, 6H ), 2.56 (d, J = 6. 6 Hz, 2 H) , 3.07- 3.23 ( m, 1H ), 3.89 (s, 2H ) , 6. 78 ( dd, J = 3. 3, 2. 1 H z, 1H ), 7.21- 7.32 (m , 1H ), 7.48 (d, J = 8.6 93 H z, 2H ), 7. 56-7. 68 ( m, 2H ), 9. 02 (br s, 1H ), 9. 21 ( s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 2. 27 m in LC /M S (E SI ) m /z; 386 [M +H ] LC /M S (E SI ) m /z; 384 [ M- H] H -N MR ( CD C l ) δ: 1. 10-1. 30 (m , 2H ), 1.50- 1.75 (m , 1H) , 1.82- 2.30 ( m, 8H ) , 2.33- 2.60 ( m, 3H) , 2. 63-2. 97 ( m, 3H) , 3. 05-3. 40 (m , 1H ), . 02-5. 33 ( m, 1H ), 6.72- 6.84 (m , 1H ), 7. 20-7. 34 (m , 1H) , 9. 15 ( br s, 94 1H ), 9. 21 ( s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 0. 44 m in LC /M S (E SI ) m /z; 343 [M +H ] LC /M S (E SI ) m /z; 341 [ M- H] H -N MR ( CD C l ) δ: 1. 04-1. 32 (m , 2H ), 1.50- 1.77 (m , 1H) , 1.81- 2.29 ( m, 8H ) , 2.33- 2.61 ( m, 3H) , 2. 65-2. 98 ( m, 3H) , 3. 09-3. 40 (m , 1H ), . 00-5. 35 ( m, 1H ), 6.73- 6.85 (m , 1H ), 7. 21-7. 35 (m , 1H) , 9. 12 ( br s, 95 1H ), 9. 21 ( s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 0. 42 m in LC /M S (E SI ) m /z; 343 [M +H ] LC /M S (E SI ) m /z; 341 [ M- H] H -N MR (C DC l ) δ: 1. 05-1. 21 (m , 2H ), 1.23 (s, 6H ), 1. 48-1. 66 (m , 1H ), 1. 79-2. 17 (m, 8H ) , 2.43 (d, J = 6. 8 H z, 2H ), 3 .00-3 .23 (m, 1H ) , 3. 05 ( s, 2H ), 6. 72-6. 82 ( m, 1H ), 7. 20-7 .32 (m , 1H) , 9.21 (s, 1H ) , 96 9. 41 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 0. 79 m in LC /M S (E SI ) m /z; 339 [M +H ] LC /M S (E SI ) m /z; 337 [ M- H] TABLE 108 E x D ata H -N MR ( CD C l ) δ: 1. 05-1. 33 (m , 2H ), 1.50- 1.80 (m , 1H) , 1.82- 2.20 ( m, 10H ), 2. 28 (d, J = 7.4 H z, 2H ), 2.4 9-2. 62 ( m, 4H ), 3.0 7-3. 44 (m , 1H ), 6.79 ( dd, J = 3.3, 2.1 H z, 1H ), 7. 20-7. 34 (m , 1H ), 9 .15 (br s, 97 1H ), 9. 22 ( s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 0. 62 m in LC /M S (E SI ) m /z; 375 [M +H ] LC /M S (E SI ) m /z; 373 [ M- H] H -N MR (D MS O- d ) δ: 1. 06-1. 30 (m, 2H) , 1. 50-1. 66 ( m, 1H) , 1. 68-1. 85 ( m, 2H ), 1. 90-2. 08 (m , 4H ), 2.42 (d, J = 6.6 H z, 1H ) , 3. 03-3. 20 (m , 1H) , 3.25- 3.38 ( m, 1H ), 3.8 1 (s, 2H ), 6. 70-6. 85 (m , 1H ), 7.40- 7.51 (m , 1H ), 7. 58 (d, J = 8 .3 H z, 2H ), 7. 67 (d, J = 8 .0 Hz , 2H ), 9. 51 ( s, 1H ), 12. 51 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 2. 95 m in LC /M S (E SI ) m /z; 429 [M +H ] LC /M S (E SI ) m /z; 427 [ M- H] H -N MR (D MS O- d ) δ: 1. 19-1. 40 (m, 2H) , 1. 65-1. 88 ( m, 3H) , 1. 95-2. 11 (m, 4H ), 2. 95-3. 07 (m , 2H ), 3.10- 3.25 (m , 1H ), 6.40- 6.52 ( m, 1H ), 6.69 ( d, J = 8. 6 Hz, 2H ), 6. 76-6. 87 (m , 1H ), 7.36 (d, J = 8.6 99 H z, 2H ), 7. 45-7. 55 ( m, 1H ), 9. 51 (s, 1H ), 12. 52 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 4. 49 m in LC /M S (E SI ) m /z; 415 [M +H ] LC /M S (E SI ) m /z; 413 [ M- H] H -N MR (D MS O- d ) δ: 1. 16-1. 40 (m, 2H) , 1. 61-1. 88 ( m, 3H) , 1. 94-2. 10 (m, 4H ), 2. 85-3. 00 (m , 2H ), 3.10- 3.25 (m , 1H ), 5.52- 5.65 ( m, 1H ) , 6.50- 6.63 ( m, 2H) , 6. 76-6. 82 ( m, 1H) , 6. 85-6. 98 (m , 2H ), 7. 49 ( t, J = 3.0, 1H) , 9.51 (s, 1H ) , 12.52 (br s, 1H ) .

LC /M S : condit i on 1, re tent ion ti m e = 3. 63 m in LC /M S (E SI ) m /z; 365 [M +H ] H -N MR (D MS O- d ) δ: 1. 10-1. 30 (m, 2H) , 1. 50-2. 10 ( m, 9H) , 3. 08-3. 21 ( m, 1H ), 3. 69-3. 90 (m , 2H ), 6.79 (d, J = 3.3 H z, 1H ) , 7. 10-7. 25 ( m, 2H ), 7. 38-7. 56 ( m, 3H ), 9. 51 ( s, 1H ), 12. 52 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 2. 67 m in LC /M S (E SI ) m /z; 379 [M +H ] LC /M S (E SI ) m /z; 377 [ M- H] H -N MR (D MS O -d ) δ: 1. 18-1. 40 (m , 2H ), 1.60- 2.10 ( m, 7H ), 2. 92 (s , 3H ), 3.05- 3.25 ( m, 3H ), 6.68 ( dd, J = 9.5, 4.2 H z, 2H) , 6. 76-6. 83 (m , 1H ), 6. 94-7. 08 (m , 2 H) , 7. 41-7. 54 ( m, 1H ), 9.50 (s, 1H ), 12.52 (br s, 102 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 80 m in LC /M S (E SI ) m /z; 379 [M +H ] LC /M S (E SI ) m /z; 377 [ M- H] H -N MR (D MS O- d ) δ: 1. 15-1. 37 (m, 2H) , 1. 65-1. 88 ( m, 3H) , 1. 91-2. 08 (m , 4H) , 2.12 ( s, 3H ), 3.05- 3.23 (m , 3H ), 5. 89-6. 00 (m , 1H ), 6. 65 (d, J = 8.6 H z, 1H ), 6. 75-6. 84 ( m, 1H ), 7 .26-7 .53 (m, 3H ) , 103 9. 51 ( s, 1H ), 12. 51 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 4. 07 m in LC /M S (E SI ) m /z; 386 [M +H ] LC /M S (E SI ) m /z; 384 [ M- H] TABLE 109 E x D ata H -N MR (D MS O- d ) δ: 1. 15-1. 38 (m, 2H) , 1. 66-1. 90 ( m, 3H) , 1. 95-2. 10 (m , 4H) , 2.13 ( s, 3H ), 2.95- 3.08 (m , 2H ), 3. 10-3. 25 (m , 1H ), 6. 56 (d, J = 8.3 H z, 1H ), 6. 76-6. 85 ( m, 1H ), 6 .91-7 .05 (m, 2H ) , 104 7. 41-7. 54 ( m, 1H ), 9. 51 ( s, 1H ), 12. 51 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 4. 67 m in LC /M S (E SI ) m /z; 445 [M +H ] LC /M S (E SI ) m /z; 443 [ M- H] H -N MR (D MS O- d ) δ: 1. 15-1. 40 (m, 2H) , 1. 65-1. 88 ( m, 3H) , 1. 95-2. 10 (m, 4H ), 3. 01-3. 25 (m , 3H ), 6.75- 6.95 (m , 2H ), 7.01- 7.12 ( m, 1H ) , 7.27- 7.39 ( m, 1H) , 7. 43-7. 53 ( m, 1H) , 7. 66-7. 77 (m , 1H ), 105 9. 51 ( s, 1H ), 12. 52 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 4. 22 m in LC /M S (E SI ) m /z; 440 [M +H ] LC /M S (E SI ) m /z; 438 [ M- H] H -N MR (D MS O- d ) δ: 1. 06-1. 29 (m, 2H) , 1. 45-1. 63 ( m, 1H) , 1. 65-1. 85 (m , 2H) , 1.89- 2.07 ( m, 4H ), 2.3 2-2. 62 (m , 2 H) , 2. 39 ( s, 3H ), 3.05- 3.20 (m , 1H ), 3.74- 3.89 (m , 2H ), 6.55- 6.67 ( m, 1H ) , 6.71 ( d, J = 3.3 H z, 1H ), 6.80 ( d, J = 2.7 H z, 1H ) , 7.42- 7.54 ( m, 1H ), 9.50 ( s, 1H) , 12.5 1 (b r s , 1H) .

LC /M S : condit i on 1, re tent ion ti m e = 2. 75 m in LC /M S (E SI ) m /z; 381 [M +H ] LC /M S (E SI ) m /z; 379 [ M- H] H -N MR (D MS O- d ) δ: 1. 06-1. 30 (m, 2H) , 1. 45-1. 63 ( m, 1H) , 1. 65-1. 87 (m, 2H) , 1. 89-2. 08 ( m, 4H) , 2. 77 ( t, J = 5.4 H z, 1H ) , 2. 81-2. 91 (m, 1H) , 3. 05-3. 20 ( m, 1H) , 4. 39 ( t, J = 5.1 H z, 1H ) , 4. 49-4. 61 (m , 1H) , 6.72- 6.85 ( m, 1H ), 7.4 0-7. 53 (m , 1 H) , 9. 51 ( s, 1H ), 12. 51 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 0. 39 m in LC /M S (E SI ) m /z; 317 [M +H ] LC /M S (E SI ) m /z; 315 [ M- H] H -N MR (D MS O -d ) δ: 1. 19-1. 42 (m , 2H ), 1.60- 2.10 ( m, 7H ), 3. 05 (s , 3H ), 3.0 7-3. 22 (m , 1H ), 3.25 -3.4 1 (m , 2H ) , 6. 70-6. 90 (m , 3H ) , 7. 40-7. 60 ( m, 3H ), 9. 50 ( s, 1H ), 12. 51 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 4. 10 m in LC /M S (E SI ) m /z; 386 [M +H ] LC /M S (E SI ) m /z; 384 [ M- H] H -N MR (C D Cl ) δ: 1. 12-1. 28 (m , 2H ), 1.33 ( d, J = 6. 6 H z, 3H ), 1. 37-2. 16 (m, 7H) , 2. 30 (dd, J = 11.4, 6.9 H z, 1H ), 2.48 (dd, J = 11. 7, 6.3 H z, 1H ), 3.15 (t t, J = 12.0, 3.3 H z, 1H ), 3. 74 (q, J = 6.3 H z, 1H ), 6.77 (d, J = 2. 4 H z, 1H ), 7. 05-7. 7.28 (m , 4H ) , 9. 23 ( s, 1H ), 9. 52 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 2. 89 m in LC /M S (E SI ) m /z; 411 [M +H ] LC /M S (E SI ) m /z; 409 [ M- H] TABLE 110 E x D ata H -N MR ( CD Cl ) δ: 1.22 ( m, 2H ), 1. 86-2. 17 (m , 7H) , 2.58 ( d, J = 6. 6 H z, 2H ), 3.1 8 (tt , J = 11. 7, 3. 6 Hz, 1H ), 3.83 ( s, 2H ), 6.77 ( m, 1H) , 7. 16-7. 39 ( m, 5H ), 9. 22 ( s, 1H ), 9. 43 ( br s, 1H) .

LC /M S : condit i on 1, re tent ion ti m e = 3. 03 m in LC /M S (E SI ) m /z; 445 [M +H ] LC /M S (E SI ) m /z; 443 [ M- H] H -N MR ( CD Cl ) δ: 1.22 ( m, 2H ), 1. 85-2. 14 (m , 7H) , 2.58 ( d, J = 6. 6 H z, 2H ), 2. 72-2. 95 (m , 4H) , 3. 16 ( tt , J = 11. 7, 3.3 H z, 1H ), 6. 78 (d, J = 3. 9 H z, 1H ), 6. 95-7. 27 ( m, 5H ), 9. 21 (s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 2. 81 m in LC /M S (E SI ) m /z; 393 [M +H ] LC /M S (E SI ) m /z; 391 [ M- H] H -N MR ( CD Cl ) δ: 1.25 ( m, 2H ), 1. 70 (m , 1H ) , 1. 86-2. 18 (m , 6H ), 2. 57 ( d, J = 6. 6 Hz, 2H ), 3. 17 ( tt , J = 11.7, 3. 6 H z, 1H) , 3.84 (s, 2H ) , 6. 78 (m , 1H) , 7.15 ( t , J = 9.9 Hz, 1H ), 7. 29 ( t, J = 2. 7 H z, 1H ), 7.54 112 ( m, 1H ), 7. 60 ( dd, J = 6. 9, 1.5 H z, 1H ), 9. 25 ( s, 1H ), 9. 60 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 2. 97 m in LC /M S (E SI ) m /z; 447 [M +H ] LC /M S (E SI ) m /z; 445 [ M- H] H -N MR ( CD Cl ) δ: 1.22 ( m, 2H ), 1. 87-2. 17 (m , 7H) , 2.57 ( d, J = 6. 6 H z, 2H) , 3.06 (s, 3H ), 3. 16 (t t, J = 12. 0, 3.3 Hz, 1H ), 3. 93 ( s, 2H) , 6. 78 ( m, 1H ) , 7.27, ( m, 1H ) , 7.58 ( d, J = 8.4 H z, 2H ), 7. 90 ( d, J = 8. 7 H z, 2H ), 9. 09 ( br s, 1H ), 9. 21 ( s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 0. 70 m in LC /M S (E SI ) m /z; 439 [M +H ] H -N MR (D MS O- d ) δ: 1 .27 (q, J = 11.4 H z, 2H ) , 1.6 8-1.8 5 ( m, 3H) , 1. 96-2. 09 (m , 4H ), 2.94 ( t, J = 5.7 H z, 1H) , 3. 17 (d , J = 5.3 H z, 2H) , . 96 ( t, J = 5.7 Hz, 1H) , 6.62 (d, J = 9. 0 H z, 2H ), 6.80 (d d, J = 3. 3, 1. 2 H z, 1H ), 7. 04 (d, J = 8. 6 H z, 2H ) , 7.48 ( t, J = 2. 5 H z, 1H ) , 9.51 ( s, 1H) , 12.5 1 (b r s , 1H) .

LC /M S : condit i on 1, re tent ion ti m e = 4. 49 m in LC /M S (E SI ) m /z; 431 [M +H ] LC /M S (E SI ) m /z; 429 [ M- H] H -N MR (D MS O- d ) δ: 1. 26 ( q, J = 11. 4 H z, 2H ), 1. 76 (q, J = 12.3 H z, 3H) , 1 .92- 2.07 ( m , 4H ), 3. 10 (t , J = 6. 1 H z, 2H) , 5 .61 ( t, J = 6.1 H z, 1H) , 6 .78- 6.82 ( m, 2H ), 7.17 (dd, J = 8.6 , 2. 5 H z, 1H) , 7.35 (dd, J = 2. 9, 0.8 H z, 1H ), 7.48 ( t, J = 2. 9 H z, 1H ), 9.51 ( s, 1H ) , 12. 51 (br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 4. 77 m in LC /M S (E SI ) m /z; 465 [M +H ] LC /M S (E SI ) m /z; 463 [ M- H] TABLE 111 E x D ata H -N MR (D MS O- d ) δ: 1.25 (q, J = 11. 4 Hz, 2 H) , 1. 67-1. 83 ( m, 3H) , 1. 91-2. 07 (m , 4H) , 3. 08-3. 22 ( m, 3H ), 6. 08 ( t , J = 5. 7 Hz, 1H) , 6. 79-6. 87 (m , 2H ), 7. 33 (t d, J = 9. 0, 3. 3 H z, 1H ), 7. 42 (dd, J = 8. 6, 116 2. 9 H z, 1H ), 7. 48 ( d, J = 2. 9 H z, 1H ) , 9.51 (s, 1H ) , 12.51 (br s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 4. 15 m in LC /M S (E SI ) m /z; 390 [ M+H ] LC /M S (E SI ) m / z; 388 [ M- H] H -N MR ( DM SO -d ) δ: 1.25 (dq, J = 12.3, 2. 5 H z, 2H ) , 1. 67-1. 83 ( m, 3H ), 1.94- 2.03 ( m, 4 H) , 3. 07-3. 22 (m , 3H ), 5.33 ( t, J = 5. 7 Hz, 1H) , 6. 80 ( d, J = 2. 9 H z, 1H ), 6. 88 (dd, J = 9. 0, 4.5 H z, 1H ), 7. 28 ( dd, J = 9. 0, 3.3 H z, 1H ), 7.33 (dd, J = 9.0, 3. 3 H z, 1H ), 7. 48 ( br s, 1H) , 9. 50 ( s, 1H) , 12. 51 ( br s , 1H) .

LC /M S : condi ti on 1, r etent ion t im e = 4. 55 m in LC /M S (E SI ) m /z; 433 [ M+H ] LC /M S (E SI ) m / z; 431 [ M- H] H -N MR (D MS O- d ) δ: 1.26 (q, J = 11. 9 Hz, 2 H) , 1. 67-1. 84 ( m, 3H) , 1. 96-2. 08 ( m, 4 H) , 2.90 ( br s, 5H ), 3.17 (t , J = 12. 3 H z, 1H ) , 3.31 ( s, 2H ), 3.71 ( t, J = 3. 7 Hz, 4H ), 6. 55 (d, J = 7. 8 H z, 2H ), 6.77 (d, J = 7. 8 H z, 2H ) , 6. 80 ( dd, J = 3. 3, 2.0 H z, 1H ) , 7. 48 ( t, J = 2. 9 H z, 1H) , 9. 51 ( s, 1H ), 12. 52 ( br s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 2. 80 m in LC /M S (E SI ) m /z; 432 [ M+H ] LC /M S (E SI ) m / z; 430 [ M- H] H -N MR ( CD Cl ) δ: 1 .06- 1.37 ( m, 2H ), 1.57- 2.37 (m, 11H ), 2.3 8-2. 47 ( m, 2H ) , 2.48- 2.59 ( m, 1H) , 2. 72-2. 87 ( m, 1H) , 2. 90-3. 04 (m , 1H ), 3. 09-3. 25 (m, 1H ), 4. 25-4. 44 (m , 1H ), 6.71- 6.87 (m , 1H ) , 7.2 2-7. 38 119 ( m, 1H ), 9. 10 ( br s, 1H ), 9. 21 ( s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 0. 39 m in LC /M S (E SI ) m /z; 341 [ M+H ] LC /M S (E SI ) m / z; 339 [ M- H] H -N MR ( CD C l ) δ: 1. 11-1. 33 ( m, 2H ), 1.4 2-1. 81 (m , 2H ), 1.83- 2.23 ( m, 10H ) , 2.51- 2.83 (m , 4H ), 3. 07-3 .25 (m , 1H ), 3. 70-3. 94 (m , 2H ), 3. 99-4. 14 ( m, 1H ), 6.72- 6.83 (m , 1H ), 7. 21-7. 35 (m , 1H) , 9. 05 ( br s, 120 1H ), 9. 21 ( s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 1. 19 m in LC /M S (E SI ) m /z; 355 [ M+H ] LC /M S (E SI ) m / z; 353 [ M- H] LC /M S : c ondi t ion 1, r etent i on t im e = 3.74, 3. 87 m in ( ci s/t rans mi xt ure) LC /M S (E SI ) m /z; 358 [ M+H ] LC /M S (E SI ) m / z; 356 [ M- H] LC /M S : condi ti on 1, r etent ion t im e = 0. 36 m in (ci s/ tr ans m ix tur e) 122 LC /M S (E SI ) m /z; 362 [ M+H ] LC /M S (E SI ) m / z; 360 [ M- H] LC /M S : condi ti on 1, r etent ion t im e = 2. 61 m in (ci s/ tr ans m ix tur e) 123 LC /M S (E SI ) m /z; 361 [ M+H ] LC /M S (E SI ) m / z; 359 [ M- H] TABLE 112 E x D ata LC /M S : condit i on 1, re tent ion ti m e = 0. 39 m in (ci s/ tr ans m ixt ure) 124 LC /M S (E SI ) m /z; 327 [M +H ] LC /M S (E SI ) m /z; 325 [ M- H] LC /M S : condit i on 1, re tent ion ti m e = 3. 04 m in (ci s/ tr ans m ixt ure) 125 LC /M S (E SI ) m /z; 429 [M +H ] LC /M S (E SI ) m /z; 427 [ M- H] LC /M S : condit i on 1, re tent ion ti m e = 0. 36 m in (ci s/ tr ans m ixt ure) 126 LC /M S (E SI ) m /z; 370 [M +H ] LC /M S (E SI ) m /z; 368 [ M- H] LC /M S : condit i on 1, re tent ion ti m e = 0. 37 m in (ci s/ tr ans m ixt ure) LC /M S (E SI ) m /z; 350 [M +H ] LC /M S (E SI ) m /z; 348 [ M- H] LC /M S : c ondi t ion 1, r etent i on t im e = 4.25, 4. 39 mi n ( ci s/t rans mi xt ure) LC /M S (E SI ) m /z; 401 [M +H ] LC /M S (E SI ) m /z; 399 [ M- H] LC /M S : condit i on 1, re tent ion ti m e = 3. 95 m in (ci s/ tr ans m ixt ure) 129 LC /M S (E SI ) m /z; 376 [M +H ] LC /M S (E SI ) m /z; 374 [ M- H] LC /M S : condit i on 1, re tent ion ti m e = 2. 79 m in (ci s/ tr ans m ixt ure) 130 LC /M S (E SI ) m /z; 365 [M +H ] LC /M S (E SI ) m /z; 363 [ M- H] LC /M S : c ondi t ion 1, r etent i on t im e = 2.84, 3. 24 mi n ( ci s/t rans mi xt ure) LC /M S (E SI ) m /z; 351 [M +H ] LC /M S (E SI ) m /z; 349 [ M- H] LC /M S : c ondi t ion 1, r etent i on t im e = 3.94, 4. 02 mi n ( ci s/t rans mi xt ure) LC /M S (E SI ) m /z; 372 [M +H ] LC /M S (E SI ) m /z; 370 [ M- H] LC /M S : condit i on 1, re tent ion ti m e = 4. 45 m in (ci s/ tr ans m ixt ure) 133 LC /M S (E SI ) m /z; 431 [M +H ] LC /M S (E SI ) m /z; 429 [ M- H] H -N MR (D MS O- d ) δ: 1. 82-1. 95 (m, 6H) , 2. 07-2. 23 ( m, 2H) , 3. 35-3. 43 (m , 1H ), 3. 67 (br s, 1H ) , 6. 77-6. 73 (m, 3H ), 6 .86 (dd, J = 2. 9, 1. 2 Hz, 1H ), 7.44 (d, J = 9. 0 Hz, 2H ), 7 .50 (t , J = 2.9 H z, 1H ) , 9. 53 ( s, 1H ), 12. 53 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 88 m in LC /M S (E SI ) m /z; 358 [M +H ] LC /M S (E SI ) m /z; 356 [ M- H] H -N MR ( DM SO -d ) δ: 1.48 (dq, J = 11.9, 3. 7 H z, 2H ) , 1. 86-2. 18 (m , 6H ), 3. 15-3. 25 (m , 1H ), 3.50 (br s, 1H) , 6.64 (d, J = 8. 1, 1H ), 6.72 ( d, J = 8. 6 Hz, 2H ), 6. 90 (dd, J = 3.3, 1. 6 H z, 1H ) , 7. 44 ( d, J = 8.6 H z, 2H ), 7. 50 ( t, J = 2. 9 H z, 1H ), 9. 52 ( s, 1H ), 12. 53 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 74 m in LC /M S (E SI ) m /z; 358 [M +H ] LC /M S (E SI ) m /z; 356 [ M- H] TABLE 113 E x D ata H -N MR (C D Cl ) δ : 1. 91 (m , 6H ), 2. 29 ( m, 2H ), 2.92 ( m, 5H ), 3.34 ( tt , J = 9.9, 3. 6H z, 1H ), 7.10 (d, J = 3. 3 H z, 1H ), 7. 18-7. 33 (m , 6H ), 135 9. 21 ( s, 1H ), 9. 69 ( br s, 1H) . a LC /M S : condit i on 1, re tent ion ti m e = 2. 78 m in LC /M S (E SI ) m /z; 361 [M +H ] LC /M S (E SI ) m /z; 359 [ M- H] H -N MR (C D Cl ) δ : 1. 30 (m , 2H ), 1. 88 ( m, 2H ), 2.07 ( m, 4H ), 2.62 ( tt , J = 11. 4, 3.3 Hz, 1H ), 2.79 (t , J = 7.5 H z, 2H ), 2.95 (t , J = 7. 2 H z, 2H ), 3.10 (t t, J = 12.3, 3.3H z, 1H ), 6. 68 (d, J = 2. 7 Hz, 1H) , 7. 12-7. 26 ( m, 6H ), 9. 15 ( s, 1H ), 9. 95 ( br s, 1H) .

LC /M S : condit i on 1, re tent ion ti m e = 2. 51 m in LC /M S (E SI ) m /z; 361 [M +H ] LC /M S (E SI ) m /z; 359 [ M- H] H -N MR (C D Cl ) δ: 1.31- 1.94 ( m, 10H ), 2.30 ( m, 1H ), 2.72 (m , 4H ) , 2. 92 ( s, 1H ), 3. 30 ( m, 1H ), 7. 14-7. 34 ( m, 7H ), 9. 21 (s, 1H ), 9. 48 ( br 136 s, 1H ). a LC /M S : condit i on 1, re tent ion ti m e = 2. 84 m in LC /M S (E SI ) m /z; 375 [M +H ] LC /M S (E SI ) m /z; 373 [ M- H] H -N MR ( CD Cl ) δ: 1.37 ( m, 2H ), 1. 80-2.0 1 (m , 5H ) , 2. 13 (m , 4H ), 2. 63 (m , 1H) , 2.70 ( t , J = 7.5 Hz, 1H ), 2. 76 ( t, J = 7. 5 H z, 1H ), 3.26 ( m, 1H ) , 3. 17 (m, 1H ), 6. 76 (d, J = 3. 6H z, 1H ), 7.16- 7.34 ( m, 6H) , 9. 21 ( br s, 1H ), 9. 21(s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 2. 76 m in LC /M S (E SI ) m /z; 375 [M +H ] LC /M S (E SI ) m /z; 373 [ M- H] H -N MR ( CD Cl ) δ: 1.37 ( m, 2H ), 1. 80-2.0 1 (m , 5H ) , 2. 13 (m , 4H ), 2. 63 (m , 1H) , 2.70 ( t , J = 7.5 Hz, 1H ), 2. 76 ( t, J = 7. 5 H z, 1H ), 3.26 ( m, 1H ) , 3. 17 (m, 1H ), 6. 76 (d, J = 3. 6H z, 1H ), 7.16- 7.34 ( m, 6H) , 9. 21 ( br s, 1H ), 9. 21(s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 2. 76 m in LC /M S (E SI ) m /z; 375 [M +H ] LC /M S (E SI ) m /z; 373 [ M- H] H -N MR (D MS O- d ) δ: 1. 56-1. 71 (m, 4H) , 1. 80-1. 90 ( m, 2H) , 2. 19-2. 35 (m, 2H ), 2. 84 (br s, 1H) , 3. 19-3. 26 (m , 1H ), 3. 84 (br s , 137 2H ), 7.08 ( d, J = 3.0 H z, 1H ), 7.43 ( t, J = 2. 6 Hz, 1H ), 7.63 (d, J = 8. 3 H z, 2H ), 7. 83 ( d, J = 8. 3 H z, 2H ), 9.52 (s, 1H ) , 12.51 (br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 1. 03 m in LC /M S (E SI ) m /z; 372 [M +H ] H -N MR (CD C l ) δ: 1.40 (dq, J = 12.6, 3. 3 Hz, 2H ) , 1.96 (dq, J = 12. 9, 4. 0 H z, 2H ) , 2. 12-2. 22 (m , 4H) , 2. 71 (t t, J = 11. 2, 3. 6 H z, 1H ) , 3. 19 ( tt , J = 12. 2, 3.3 H z, 1H) , 3.96 (s, 2H ), 6. 77 ( dd, J = 3. 6, 2.3 137 H z, 1H ), 7.30 ( t, J = 3. 0 H z, 1H) , 7. 50 (d, J = 7.9 H z, 2H ), 7.64 ( d, J b = 8. 3 H z, 2H ), 9. 14 ( br s, 1H ), 9. 23 ( s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 0. 85 m in LC /M S (E SI ) m /z; 372 [M +H ] LC /M S (E SI ) m /z; 370 [ M- H] TABLE 114 E x D ata H -N MR (C DC l ) δ: 1. 74 (t, J = 3.3 H z, 1 H) , 1.76 -1.8 7 ( m, 4H ) , 1.95 ( br s, 2H ) , 2. 27-2. 42 ( m, 2H) , 2. 99-3. 05 ( m, 1H) , 3. 29-3. 41 (m , 1H ), 3. 91 (s , 2H ), 7. 10 (dd, J = 3. 3, 2. 0 H z, 1H ) , 7. 19 ( t, J = 2. 6 H z, 138 1H ), 7. 53 ( d, J = 8.3 H z, 2H) , 7.6 1 (d , J = 8. 3 Hz, 2H ) , 9.23 (s , 1H) , a 9. 31 ( br s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 2. 87 m in LC /M S (E SI ) m /z; 415 [ M+H ] LC /M S (E SI ) m / z; 413 [ M- H] H -N MR (D MS O -d ) δ: 1. 35 (q, J = 10. 6 H z, 2 H) , 1. 76 (q, J = 1 2.2 H z, 2H ), 1.95- 2.14 ( m, 4H ), 2. 19-2 .32 (m , 1H ) , 3.1 5 ( t, J = 12.2 H z, 1H ), 3.89 ( s, 2H ), 6.80 (d, J = 2. 6 Hz, 1H ), 7 .49 (br s, 1H ), 7.61 ( d, 138 J = 8 .6 H z, 2H ), 7. 69 ( d, J = 8. 3 H z, 2H ), 9. 52 (d, J = 1.3 H z, 1H ) , b 12. 53 ( br s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 2. 72 m in LC /M S (E SI ) m /z; 415 [ M+H ] LC /M S (E SI ) m / z; 413 [ M- H] H -N MR (C DC l ) δ: 1.6 4-1. 78 ( m, 5H ), 1.90- 1.99 (m , 2H ), 2. 33 ( dq, J = 13.2, 3.0 H z, 2H ), 2. 74 (br s, 4H ) , 3.21 ( t, J = 3. 3 H z, 1H) , 139 3. 27-3. 38 (m , 1H ), 3.75 (t , J = 4.6 Hz, 4H ) , 7 .23 ( dd, J = 3. 6, 2.0 H z, 1H ), 7. 28 ( t, J = 3. 0 H z, 1H ), 9. 21 ( br s, 1H ), 9. 22 ( s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 0. 79 m in LC /M S (E SI ) m /z; 342 [ M+H ] H -N MR (C D Cl ) δ: 1. 37 (dq, J = 12.9, 4. 0 H z, 2H ), 1.57 (br s, 1H ) , 1. 96 ( dq, J = 12. 6, 3 .0 H z, 2H ), 2. 08-2. 19 ( m, 4H ), 2. 69 ( br s, 4H ) , 2. 94 (t t, J = 11.2, 3.3 Hz, 1H ), 3. 18 ( tt , J = 12.2, 4. 0 H z, 1H) , 3 .76 ( t, J = 4.6 H z, 4H ), 6.78 (dd , J = 3.3, 2. 3 H z, 1H ) , 7.29 ( t, J = 2.6 H z, 1H ), 9. 09 ( br s, 1H ), 9. 22 ( s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 0. 57 m in LC /M S (E SI ) m /z; 342 [ M+H ] H -N MR ( DM SO -d ) δ: 4.59 (d, J = 5.4 H z, 2H ), 5. 27 (t , J = 6.0 Hz , 1H ), 6.86 ( m, 1H ) , 7. 54 (m , 3H ), 7.92 (d , J = 8. 1 H z, 2H ), 9.65 ( s, 1H ), 12. 68 (br s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 2. 77 m in LC /M S (E SI ) m /z; 266 [ M+H ] LC /M S (E SI ) m / z; 264 [ M- H] H -N MR (D MS O -d ) δ: 1. 25 (m , 2H ), 1.66 ( m, 1H ), 1.87 ( m, 2H) , 2. 00-2. 15 (m , 4H) , 3. 18 ( tt , J = 12.3 H z, 3.6 Hz , 1H ) , 3. 47 (d, J = 6. 6 H z, 2 H) , 6. 81 H z ( d, J = 3. 3 Hz, 1H) , 7. 38 (d, J = 3. 3 Hz, 1H) , 141 9. 28 ( s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 2. 80 m in LC /M S (E SI ) m /z; 272 [ M+H ] LC /M S (E SI ) m / z; 270 [ M- H] H -N MR ( DM S O- d ) δ: 1 .88- 2.06 (m , 4H ) , 2.19- 2.32 (m, 2H ) , 2. 92-3. 02 (m , 2H ), 3.10- 3.14 (m , 1H ) , 3. 62 ( s, 2H ) , 6. 82 ( br s, 1H ) , 7. 13-7. 25 (m , 2H) , 7 .27- 7.40 ( m, 1H ), 7.45- 7.53 (m , 2H ), 9. 52 (s , 1H ), 12. 52 (br s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 1. 33 m in LC /M S (E SI ) m /z; 351 [ M+H ] LC /M S (E SI ) m / z; 349 [ M- H] TABLE 115 E x D ata H -N MR ( DM S O- d ) δ: 1 .88- 2.05 (m , 4H ) , 2.21- 2.35 (m, 2H ) , 2. 94-3. 03 (m , 2H) , 3. 10-3. 24 (m , 1H ), 3.68 ( s, 2H) , 6.58 ( d, J = 3.3 H z, 1H ), 6.81 (d, J = 3.3 H z, 1H) , 7.15- 7.20 (m , 1H ), 7.46 -7.52 (m , 143 1H ), 9. 52 ( s, 1H ), 12. 52 ( br s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 1. 52 m in LC /M S (E SI ) m /z; 391 [ M+H ] LC /M S (E SI ) m / z; 389 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 1. 22 m in 144 LC /M S (E SI ) m /z; 364 [ M+H ] LC /M S (E SI ) m / z; 362 [ M- H] H -N MR ( CD Cl ) δ: 1.97- 2.11 (m , 2H ), 2. 12-2. 33 ( m, 4H) , 2.97- 3.10 ( m, 2H) , 3.15- 3.31 ( m, 1H ), 3.59 (s, 2H ), 6.80- 6.87 (m, 1H ), 6.93 ( dd, J = 8. 4, 2.7 H z, 1H ) , 7. 31 (t , J = 3.0 H z, 1H) , 7. 80-7. 90 (m , 1H ), 8. 15-8. 20 (m, 1H ), 9. 15 (br s, 1H ), 9. 23 ( s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 1. 58 m in LC /M S (E SI ) m /z; 411, 413 [ M+H ] H -N MR ( DM S O- d ) δ: 1 .90- 2.04 (m , 4H ) , 2.19- 2.31 (m, 2H ) , 2. 92-3. 03 (m , 2H) , 3 .06- 3.20 ( m, 1H ), 3.57 (s, 2H ), 6.30 -6.3 5 (m , 1H ), 6.40- 6.45 (m , 1H ), 6.78- 6.84 (m , 1H ), 7.47- 7.53 (m , 1H ), 7.60 ( s, 1H) , 9.5 2 (s , 1H) , 12.52 (br s , 1H) .

LC /M S : condi ti on 3, r etent ion t im e = 1. 14 m in LC /M S (E SI ) m /z; 323 [ M+H ] H -N MR ( DM S O- d ) δ: 1 .84- 2.06 (m , 4H ) , 2.15- 2.33 (m, 2H ) , 2. 87-3. 04 (m , 2H) , 3. 06-3. 22 (m , 1H ), 3.58 ( s, 2H) , 6.29 ( d, J = 3.3 H z, 1H) , 6 .63 (d, J = 3. 3 H z, 1H) , 6.81 ( br s, 1H) , 7.44- 7.51 (m , 147 1H ), 9. 51 ( s, 1H ), 12. 52 ( br s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 1. 44 m in LC /M S (E SI ) m /z; 449 [ M+H ] LC /M S (E SI ) m / z; 447 [ M- H] H -N MR ( DM S O- d ) δ: 1 .86- 2.10 (m , 4H ) , 2.18- 2.33 (m, 2H ) , 2. 94-3. 10 (m , 2H ), 3.11- 3.26 (m , 1H ) , 3. 76 ( s, 2H ) , 6. 82 ( br s, 1H ) , 6. 91-7. 03 (m , 2H) , 7 .40- 7.46 ( m, 1H ), 7.46- 7.53 (m , 1H ), 9. 52 (s , 148 1H ), 12. 52 (br s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 1. 24 m in LC /M S (E SI ) m /z; 339 [ M+H ] LC /M S (E SI ) m / z; 337 [ M- H] H -N MR ( DM S O- d ) δ: 1 .84- 2.06 (m , 4H ) , 2.17- 2.33 (m, 2H ) , 2. 88-3. 04 (m , 2H) , 3. 05-3. 22 (m , 1H ), 3.57 ( s, 2H) , 6.40 ( d, J = 3.3 H z, 1H) , 6 .51 (d, J = 3. 3 H z, 1H) , 6.81 ( br s, 1H) , 7.43- 7.52 (m , 1H ), 9. 51 ( s, 1H ), 12. 52 ( br s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 1. 39 m in LC /M S (E SI ) m /z; 401, 403 [ M+H ] H -N MR ( DM S O- d ) δ: 1 .85- 2.08 (m , 4H ) , 2.20- 2.37 (m, 2H ) , 2. 94-3. 05 (m , 2H ), 3.11- 3.27 (m , 1H ) , 3. 78 ( s, 2H ) , 6. 82 ( br s, 1H ) , 7. 46-7. 53 ( m, 1H ), 7. 58 ( s, 1H ), 9. 52 ( s, 1H ), 12. 52 ( br s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 1. 21 m in LC /M S (E SI ) m /z; 374 [ M+H ] LC /M S (E SI ) m / z; 372 [ M- H] TABLE 116 E x D ata H -N MR (D MS O- d ) δ: 1. 82-2. 08 (m, 4H) , 2. 12-2. 28 ( m, 2H) , 2. 86-3. 05 (m, 2H ), 3. 05-3. 20 (m , 1H ), 3.46- 3.65 (m , 2H ), 6.09- 6.23 ( m, 1H ), 6.8 1 (br s, 1H ), 7. 48 (br s, 1H ), 9. 52 ( s, 1 H) , 12.52 ( br s, 151 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 0. 63 m in LC /M S (E SI ) m /z; 323 [M +H ] LC /M S (E SI ) m /z; 321 [ M- H] H -N MR (D MS O- d ) δ: 1. 87-2. 12 (m, 4H) , 2. 25-2. 42 ( m, 2H) , 2. 97-3. 10 (m , 2H ) , 3. 10-3. 25 (m , 1H ) , 4. 13 (s , 2H ), 6. 82 (br s, 1H) , 7. 45-7. 53 ( m, 1H ), 9. 10 ( s, 1H ), 9. 52 ( s, 1H ), 12. 52 ( br s , 1H) .

LC /M S : condit i on 3, re tent ion ti m e = 0. 81 m in LC /M S (E SI ) m /z; 341 [M +H ] LC /M S (E SI ) m /z; 339 [ M- H] H -N MR (D MS O- d ) δ: 1. 85-2. 06 (m, 4H) , 2. 20-2. 36 ( m, 2H) , 2. 92-3. 05 (m , 2H ) , 3. 12-3. 27 (m , 1H ) , 3. 80 (s , 2H ), 6. 82 (br s, 1H) , 7. 48-7. 53 ( m, 1H ), 7. 59 ( s, 1H ), 9. 52 ( s, 1H ), 12. 52 ( br s , 1H) .

LC /M S : condit i on 3, re tent ion ti m e = 1. 58 m in LC /M S (E SI ) m /z; 418, 4 20 [ M+H ] LC /M S (E SI ) m /z; 416, 418 [ M- H] H -N MR (D MS O -d ) δ: 1.96- 2.03 ( m, 4H) , 2. 23-2. 29 (m , 2H ), 2.94 (d, J = 11.4 H z, 2H) , 3. 16-3. 21 ( m, 1H ), 3. 63 ( s, 2H ), 6. 82 ( d, J = 2.4 H z, 1H ), 7. 46-7. 52 ( m, 2H ) , 7.74 (d, J = 7. 5 Hz, 2H) , 9.52 (s , 1H ), 154 12. 55 ( br s, 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 1. 68 m in LC /M S (E SI ) m /z; 419 [M +H ] LC /M S (E SI ) m /z; 417 [ M- H] H -N MR (D MS O -d ) δ: 1.95- 2.06 ( m, 4H) , 2. 23-2. 30 (m , 2H ), 2.94 (d, J = 11.7 H z, 2H) , 3. 16-3. 19 ( m, 1H ), 3. 65 ( s, 2H ), 6. 82 ( d, J = 3.3 H z, 1H ), 7.49 ( d, J = 3. 3 Hz, 1H ), 7. 71 (s, 2H) , 7. 84 (s, 1H ), 9.52 ( s, 155 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 1. 79 m in LC /M S (E SI ) m /z; 435, 4 37 [ M+H ] LC /M S (E SI ) m /z; 433, 435 [ M- H] H -N MR (D MS O -d ) δ: 1.96- 2.04 ( m, 4H) , 2. 23-2. 30 (m , 2H ), 2.96 (d, J = 10.2 H z, 2H) , 3. 22 ( s, 3H ), 3. 67 ( s, 2H ), 6. 81 ( d, J = 3.0 H z, 1H) , 7. 49 (d, J = 3.3 H z, 1H ) , 7. 65 (d, J = 8. 4 H z, 2H) , 7.91 ( d, J = 8.7 156 H z, 2H ), 9. 49 ( s, 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 1. 12 m in LC /M S (E SI ) m /z; 411 [M +H ] LC /M S (E SI ) m /z; 409 [ M- H] H -N MR (D MS O -d ) δ: 1.95- 2.07 ( m, 4H) , 2. 27-2. 33 (m , 2H ), 2.98 (d, J = 11.7 H z, 2H) , 3. 15-3. 18 ( m, 1H ), 3. 70 ( s, 2H ), 6. 82 ( d, J = 3.0 H z, 1H ) , 7. 49 (d, J = 3. 3 H z, 1H ) , 7. 61-7. 68 (m , 2H ), 7.7 6 (t, J = 7.7 157 H z, 1H ), 9. 51 ( s, 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 1. 66 m in LC /M S (E SI ) m /z; 419 [M +H ] LC /M S (E SI ) m /z; 417 [ M- H] TABLE 117 E x D ata H -N MR (D MS O- d ) δ: 1.94- 2.04 (m , 4H ), 2. 26 ( td, J = 10. 8, 3.5 H z, 2H ), 2. 95 (d , J = 11.7 Hz, 2H ), 4. 12 (s , 2H ) , 6.82 (d, J = 3.0 H z, 1H ), 7. 31 (dd, J = 8. 4, 2. 1 H z, 1H ), 7.41 (dd, J = 9.9, 2. 1 H z, 1H) , 7. 49-7. 54 ( m, 2H ), 9. 53 ( s, 1H ), 12. 54 ( br s, 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 1. 54 m in LC /M S (E SI ) m /z; 385, 3 87 [ M+H ] H -N MR (D MS O -d ) δ: 1.95- 2.06 ( m, 4H) , 2. 21-2. 27 (m , 2H ), 2.94 (d, J = 11.4 H z, 2H) , 3. 15-3. 22 ( m, 1H ), 3. 57 ( s, 2H ), 6. 83 ( d, J = 3.3 H z, 1H ), 7.25 ( d, J = 7.8 H z, 1H) , 7. 40 (d, J = 10. 8 Hz , 1H ), 7.50 (d, J = 3.3 H z, 1H ) , 7. 56 (t , J = 8.1 Hz, 1H ), 9.53 ( s, 1H ), 12.54 ( br s, 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 1. 58 m in LC /M S (E SI ) m /z; 385, 3 87 [ M+H ] LC /M S (E SI ) m /z; 383, 385 [ M- H] H -N MR ( CD C l ) δ: 1. 99-2. 13 (m , 2H ), 2.17- 2.37 (m , 4H) , 2.94- 3.10 ( m, 2H) , 3. 16-3. 32 (m , 1H ) , 3. 59 (s, 2H ), 6. 80-6 .88 (m , 1H ) , 7. 21-7. 35 (m , 2H ) , 7. 41 (s, 1H ), 8.34 (d, J = 5.1 H z, 1H ), 9.18 ( br s, 160 1H ), 9. 24 ( s, 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 1. 16 m in LC /M S (E SI ) m /z; 368, 3 70 [ M+H ] LC /M S (E SI ) m /z; 366, 368 [ M- H] H -N MR ( CD C l ) δ: 2. 00-2. 16 (m , 2H ), 2.16- 2.42 (m , 4H) , 3.00- 3.15 ( m, 2H) , 3. 15-3. 30 (m , 1H ) , 3. 71 (s, 2H ), 6. 80-6 .90 (m , 1H ) , 7. 28-7. 37 (m, 1H) , 7. 53 ( t, J = 5. 4 Hz, 1 H) , 8. 38-8. 50 ( m, 2H) , 161 9. 11-9. 30 ( m, 2H ).

LC /M S : condit i on 3, re tent ion ti m e = 0. 86 m in LC /M S (E SI ) m /z; 352 [M +H ] LC /M S (E SI ) m /z; 350 [ M- H] H -N MR ( CD C l ) δ: 2. 00-2. 10 (m , 2H ), 2.16- 2.42 (m , 4H) , 3.01- 3.15 ( m, 2H ), 3. 16-3. 32 ( m, 1H ), 3.74 (s, 2H ), 6. 80-6. 89 (m, 1H ) , 7.29 (t , J = 3. 0 H z, 1H ), 7.40 ( td, J = 8. 7, 3. 0 H z, 1H ), 7.54 ( dd, J = 8. 4, 4. 5 H z, 1H ), 8. 42 ( d, J = 2. 7 H z, 1H ), 9. 08 (br s, 1H ), 9 .22 (s, 1H ) .

LC /M S : condit i on 3, re tent ion ti m e = 1. 17 m in LC /M S (E SI ) m /z; 352 [M +H ] LC /M S (E SI ) m /z; 350 [ M- H] H -N MR ( CD C l ) δ: 2. 00-2. 15 (m , 2H ), 2.19- 2.50 (m , 4H) , 3.02- 3.14 ( m, 2H) , 3. 18-3. 33 (m , 1H ) , 3. 70 (s, 2H ), 6. 82-6 .91 (m , 1H ) , 7. 29-7. 38 ( m, 1H ) , 7. 59 ( d, J = 4. 8 H z, 1H) , 8. 48 ( d, J = 4. 8 Hz, 1H) , 8. 54 ( s, 1H ), 9. 09 ( br s, 1H) , 9.23 (s , 1H) .

LC /M S : condit i on 3, re tent ion ti m e = 1. 13 m in LC /M S (E SI ) m /z; 368, 3 70 [ M+H ] H -N MR (D MS O -d ) δ: 1.93- 2.00 ( m, 4H) , 2. 21-2. 27 (m , 2H ), 2.95 (d, J = 1 0.5 H z, 2H ), 3.59 (s, 2H ), 6. 81 ( d, J = 2.4 Hz, 1H ) , 7 .10 (t, J = 8. 4 H z, 1H ), 7. 21 (t , J = 9.3 H z, 1H ), 7. 48-7. 56 (m, 2H) , 9.52 (s , 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 1. 39 m in LC /M S (E SI ) m /z; 369 [M +H ] TABLE 118 E x D ata H -N MR (D MS O- d ) δ: 1.95- 2.07 (m , 4H ), 2. 23 ( td, J = 11. 3, 3.0 H z, 2H ), 2. 97 (d , J = 11.1 Hz, 2H ), 3. 62 (s , 2H ) , 6.83 (d, J = 3.3 H z, 1H ), 7. 25 ( td, J = 8. 6, 2.6 H z, 1H) , 7.43 (dd , J = 8. 9, 2.6 H z, 1H) , 7. 50 ( d, J = 3. 3 H z, 1H ) , 7.60 (dd, J = 8.6, 6. 2 Hz, 1H ), 9 .52 (s, 1H ) .

LC /M S : condit i on 3, re tent ion ti m e = 1. 50 m in LC /M S (E SI ) m /z; 385, 3 87 [ M+H ] H -N MR (D MS O- d ) δ: 1.91- 2.06 (m , 4H ), 2. 23 ( td, J = 11. 2, 3.1 H z, 2H ), 2. 94 (d , J = 11.7 Hz, 2H ), 3. 55 (s , 2H ) , 6.82 (d, J = 3.3 H z, 1H ), 7. 19-7. 24 (m, 1H ) , 7.35- 7.45 (m , 2H) , 7. 50 ( d, J = 3. 3 Hz, 1H ) , 166 9. 52 ( s, 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 1. 45 m in LC /M S (E SI ) m /z; 369 [M +H ] LC /M S (E SI ) m /z; 367 [ M- H] H -N MR (D MS O -d ) δ: 1.92- 2.09 ( m, 4H) , 2. 25-2. 31 (m , 2H ), 2.96 (d, J = 12.0 H z, 2H ) , 3.67 (s, 2H ) , 6.82 (d, J = 3.3 H z, 1H) , 7.43- 7.52 ( m, 3H ), 7. 77 ( t, J = 8. 0 H z, 1H ), 9. 51 ( s, 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 1. 71 m in LC /M S (E SI ) m /z; 419 [M +H ] LC /M S (E SI ) m /z; 417 [ M- H] H -N MR (D MS O -d ) δ: 1. 91-2. 23 ( m, 8H ), 2.91 (t , J = 11. 6 H z, 1H) , 3. 46 ( s, 2H ), 3. 69-3.71 (m , 2H ), 3. 96 ( br s , 2H) , 6.71 (s, 1 H) , 6.90 ( t, J = 6.8 H z, 2H ), 7.2 5 (t , J = 8.3 H z, 2H ), 7. 43 ( s, 1H ), 9. 37 (s , 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 1. 15 m in LC /M S (E SI ) m /z; 393 [M +H ] H -N MR ( CD C l ) δ: 1. 98-2. 13 (m , 2H ), 2.13- 2.34 (m , 4H) , 2.98- 3.16 ( m, 2H) , 3. 16-3. 32 (m , 1H ), 3.59 ( s, 2H ) , 5. 91 (t t, J = 56. 1, 3. 0 H z, 1H ), 6. 81-6. 90 (m, 1H ) , 7.18 (d, J = 8. 4 H z, 2H ), 7 .27-7 .33 (m, 1H ) , 169 7. 41 ( d, J = 8. 4 H z, 2H ) , 9.19 (br s, 1H ), 9. 23 ( s, 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 1. 72 m in LC /M S (E SI ) m /z; 449 [M +H ] LC /M S (E SI ) m /z; 447 [ M- H] H -N MR ( CD C l ) δ: 1. 96-2. 12 (m , 2H ), 2.12- 2.35 (m , 4H) , 3.00- 3.16 ( m, 2H ), 3.1 6-3. 31 (m , 1H) , 3.54 (s, 2H) , 3.95 (s, 3H ), 6. 75 (d, J = 8. 1 Hz, 1H ), 6.81- 6.90 ( m, 1H) , 7. 27-7. 36 (m , 1H ), 7. 64 (dd, J = 8. 4, 2. 4 H z, 1H ), 8. 11 ( d, J = 2. 1 H z, 1H ), 9.23 (s, 1H ) , 9.51 (br s, 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 1. 22 m in LC /M S (E SI ) m /z; 364 [M +H ] LC /M S : condit i on 3, re tent ion ti m e = 1. 40 m in LC /M S (E SI ) m /z; 386 [M +H ] TABLE 119 Ex D ata H -N MR (C DC l ) δ: 1.1 2-1.2 8 (m, 2H) , 1.6 2 (m, 1H) , 1.8 4-2.0 2 (m, 4H ), 2 .15 (m , 2H ), 2 .52 ( dd, J = 12 .0, 6 .9 H z, 1H) , 2. 66 (dd , J = 12 .0, 6.6 H z, 1H) , 2.98 ( d , J = 1 2.9 Hz, 1H ), 3.1 5 (t t, J = 12. 3, 3 .3 H z, 1H ), 3 .54 ( d , J = 12 .9 H z, 1 H ), 6.7 8 (m, 1 H ), 7.33 -7.40 (m, 4H) , 17 2 7.6 0 (m , 2H ), 9.2 2 (s , 1H ), 9 .45 (b r s, 1H ).

LC /M S: co ndi tion 1, ret enti on time = 2.81 mi n LC /M S(ESI ) m /z; 4 59 [M+ H ] LC /M S(ESI ) m/z ; 45 7 [M -H ] H -N MR (D MSO - d ) δ: 1. 23- 1 .38 (m, 2H ), 1. 71- 1 .86 (m, 2H) , 1.9 5-2.0 9 (m , 4H) , 3 .08 -3.23 (m , 3 H), 6.8 2 (dd, J = 1.7, 3.3 H z, 1H) , 6.8 6 (d , J = 9.2 H z, 2 H), 7.5 0 ( t, J = 3 .0 H z, 1H) , 7 .59 ( t, J = 5.6 H z, 17 3 1H ), 7 .68 (d , J = 8 .9 H z , 2H) , 9 .52 (s , 1 H), 12.5 4 (br s , 1 H).

LC /M S: co ndi tion 1, ret enti on time = 4.30 mi n LC /M S(ESI ) m /z; 4 79 [M+ H ] LC /M S(ESI ) m/z ; 47 7 [M -H ] H -N MR (C D O D ) δ : 1.1 7-1.3 3 (m , 2H) , 1.70 -1.78 (m, 1 H), 1 .78 -1 .90 (m, 2H ), 1 .93-2 .01 (m , 2 H ), 2 .06-2 .15 ( m , 2H ), 2 .66 ( d , J = 7 .0 H z, 2H ), 2.79 - 3.02 (m, 5H ), 3.1 7 (tt, J = 12 .3, 3.3 H z, 1H ), 6.79 (d, J = 3.3 Hz , 1H) , 7. 16-7 .32 (m , 6H ), 7 .38 (d , J = 3.3 Hz , 1H ), 9 .27 (b r s, 17 4 1H ).

LC /M S: co ndi tion 1, ret enti on time = 2.75 mi n LC /M S(ESI ) m /z; 3 75 [M+ H ] LC /M S(ESI ) m/z ; 37 3 [M -H ] H -N MR (D MSO - d ) δ: 1. 24- 1 .39 (m, 2H ), 1. 71- 1 .87 (m, 3H) , 2.0 1-2.0 9 (m , 5H ) , 3.0 0 ( d, J = 5.9 H z , 2H ) , 3 .13-3 .25 (m , 1H) , 5 .94 (bs , 1H ), 6 .57 (b r s, 1 H ), 6.7 9-6.8 3 (m, 2H) , 7.4 4 (d, J = 8.9 H z, 17 5 1H ), 7 .50 (t , J = 3. 0 H z, 1H ), 9.5 2 (s , 1H ), 1 2.53 (br s , 1H ).

LC /M S: co ndi tion 1, ret enti on time = 3.35 mi n LC /M S(ESI ) m /z; 4 55 [M+ H ] LC /M S(ESI ) m/z ; 45 3 [M -H ] H -N MR (D MSO - d ) δ: 1. 19- 1 .34 (m, 2H ), 1. 69- 1 .84 (m, 3H) , 1.9 6-2.0 7 (m , 4 H ), 2.9 3 (t, J = 5.6 H z, 2H) , 3 .11-3 .25 (m, 1H ), 5 .89 (t, J = 5.6 H z, 1H ), 6.5 6-6. 62 (m , 2H) , 6 .81 (dd, J = 3 .0, 1.7 Hz , 1H) , 7.0 5-7.1 1 (m , 2H) , 7.49 ( t, J = 3 .0 H z , 1 H ), 9.5 2 ( s , 1H) , 12.5 3 ( b r s, 17 6 1H ).

LC /M S: co ndi tion 1, ret enti on time = 4.32 mi n LC /M S(ESI ) m /z; 3 81 [M+ H ] LC /M S(ESI ) m/z ; 37 9 [M -H ] H -N MR (CD C l ) δ: 1.24 ( m , 2H) , 1.76 (m , 1 H) , 1 .86-2 .17 (m , 6 H ), 2.5 7 (d, J = 6. 6 H z, 1H) , 3 .16 (t t, J = 12. 3, 3. 6 Hz, 1H ), 3. 81 ( s , 2H) , 6.7 7 (d, J = 3 .3 Hz, 1H ) , 7.2 6-7.2 9 (m, 5H ), 9.2 2 ( s, 1H ), 9.7 0 ( br s , 17 7 1H ).

LC /M S: co ndi tion 1, ret enti on time = 2.84 mi n LC /M S(ESI ) m /z; 3 95 , 39 7 [M +H ] LC /M S(ESI ) m/z ; 39 3, 3 95 [ M-H ] TABLE 120 E x D ata H -N MR (C D Cl ) δ : 1. 19 (m , 2H ), 1. 66 ( m, 1H ), 1.90 ( m, 4H ), 2.12 ( m, 2H ) , 2. 57 (d, J = 6 .6 H z, 2H ) , 2. 70-2. 97 (m , 4H ), 3.16 ( tt , J = 12. 6, 3.3 H z, 1H ), 6. 77 ( d, J = 3. 3 H z, 1H ), 7.15 (m , 3H) , 7.27 (m , 178 2H ), 9. 21 ( s, 1H ), 9. 33 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 2. 97 m in LC /M S (E SI ) m /z; 409, 4 11 [ M+H ] LC /M S (E SI ) m /z; 407, 409 [ M- H] H -N MR ( CD C l ) δ: 1. 17-1. 39 (m , 2H ), 1.71- 2.28 (m , 7H) , 2.86- 3.06 ( m, 4H ) , 3.10- 3.30 ( m, 1H) , 3. 33-3. 55 ( m, 2H) , 6. 30-6. 43 (m , 1H ), 6. 70-6. 88 ( m, 3H ), 7. 20-7. 39 ( m, 1H ), 9. 02 ( br s, 1H ), 9. 22 ( s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 4. 40 m in LC /M S (E SI ) m /z; 391 [M +H ] LC /M S (E SI ) m /z; 389 [ M- H] H -N MR ( CD C l ) δ: 1. 04-1. 28 (m , 2H ), 1.46- 1.73 (m , 1H) , 1.82- 2.02 ( m, 2H ) , 2.04- 2.23 ( m, 4H) , 2. 39-2. 60 ( m, 6H) , 2. 84-3. 00 (m , 4H ), 3. 09-3. 28 ( m, 1H ), 6.72- 6.83 (m , 1H ), 7. 27-7. 37 (m , 1H) , 8. 99 ( br s, 180 1H ), 9. 21 ( s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 38 m in LC /M S (E SI ) m /z; 377 [M +H ] LC /M S (E SI ) m /z; 375 [ M- H] H -N MR ( CD C l ) δ: 1. 00-1. 31 (m , 2H ), 1.50- 1.80 (m , 1H) , 1.81- 2.18 ( m, 7H) , 2. 24 (s , 6H ), 2.26- 2.59 ( m, 4H ), 2.68- 2.92 ( m, 3H) , 3. 08-3. 24 (m, 1H ), 6. 71-6. 83 (m , 1H ), 7.17- 7.33 (m , 1H ), 9.00- 9.40 181 ( m, 1H ), 9. 21 ( s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 0. 34 m in LC /M S (E SI ) m /z; 368 [M +H ] LC /M S (E SI ) m /z; 366 [ M- H] H -N MR ( CD C l ) δ: 1. 00-1. 32 (m , 2H ), 1.40- 1.80 (m , 1H) , 1.82- 2.21 ( m, 7H ), 2.29 (s , 3H) , 2.58 ( d, J = 6.6 H z, 2H ), 3. 08-3. 25 ( m, 1H ) , 3. 76 (s, 2H ), 5.89 ( d, J = 2. 1 H z, 1H ) , 6. 06 (d, J = 3.0 H z, 1H ), 6.78 ( d, J = 3.0 H z, 1H ), 7. 17-7. 32 (m , 1H ), 9. 00-9. 40 ( m, 1H) , 9.21 (s , 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 2. 49 m in LC /M S (E SI ) m /z; 365 [M +H ] LC /M S (E SI ) m /z; 363 [ M- H] H -N MR ( CD C l ) δ: 1. 11-1. 35 (m , 2H ), 1.40- 1.81 (m , 1H) , 1.83- 2.25 ( m, 7H ), 2.57 (s , 3H) , 2.62 ( d, J = 6.6 H z, 2H ), 3. 07-3. 27 ( m, 1H ) , 3. 96 (s , 2H ) , 6. 70-6. 85 ( m, 1H ), 7.10- 7.37 (m , 1H ), 8. 35-8. 46 (m , 183 1H ), 8. 49-8. 59 ( m, 1H ), 9. 00-9. 40 (m, 1H ) , 9.21 (s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 0. 77 m in LC /M S (E SI ) m /z; 377 [M +H ] LC /M S (E SI ) m /z; 375 [ M- H] H -N MR ( CD C l ) δ: 1. 11-1. 38 (m , 5H ), 1.55- 2.35 (m , 9H) , 2.40- 2.85 ( m, 4H ), 3.09- 3.27 (m , 1H ), 3. 72-3. 92 (m , 1H) , 6.80 (d, J = 3. 3 H z, 1H ), 7. 30 ( d, J = 3 .3 H z, 1 H) , 8.60- 10.00 (m , 1H) , 9.2 3 (s , 1H) .

LC /M S : condit i on 1, re tent ion ti m e = 0. 39 m in LC /M S (E SI ) m /z; 329 [M +H ] LC /M S (E SI ) m /z; 327 [ M- H] TABLE 121 E x D ata H -N MR ( CD C l ) δ: 1. 10-1. 50 ( m, 5H ), 1.5 5-2. 35 (m , 9H ), 2.40- 2.90 ( m, 4H ), 3.10- 3.31 (m , 1H ), 3. 75-4. 00 (m , 1H) , 6.80 (d, J = 3. 3 H z, 1H ), 7. 30 ( d, J = 3.3 H z, 1H) , 8.80- 10.00 (m , 1H ), 9. 23 ( s, 1H) .

LC /M S : condi ti on 1, r etent ion t im e = 0. 37 m in LC /M S (E SI ) m /z; 329 [ M+H ] LC /M S (E SI ) m / z; 327 [ M- H] H -N MR (C D OD ) δ: 1. 30 (m , 2H ) , 1.70 -2.1 5 ( m, 7H ), 2. 74 (t , J = 6.6 H z, 2H ) , 2. 92 (d, J = 6.6 H z, 2H) , 3. 21 ( tt , J = 12. 0, 4. 2 H z, 1H) , 4. 92 ( m, 1H ), 6.82 (d, J = 3. 3 H z, 1H ), 6 .83- 7.43 (m , 6H) , 9.30 ( s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 2. 52 m in + + - - LC /M S (E SI ) m /z; 391 [ M+H ] , LC /M S( ES I ) m /z; 38 9 [ M-H ] H -N MR ( CD C l ) δ: 1. 07-1. 31 ( m, 2H ), 1.4 7-1. 74 (m , 1H ), 1.80- 2.32 ( m, 8H ) , 2.34- 2.49 ( m, 2H) , 2. 55-2. 80 ( m, 3H) , 2. 88-3. 25 (m , 3H ), 6. 71-6. 86 ( m, 1H ), 7. 18-7. 39 ( m, 1H ), 9. 01 (br s, 1H ), 9. 21 ( s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 1. 14 m in LC /M S (E SI ) m /z; 350 [ M+H ] LC /M S (E SI ) m / z; 348 [ M- H] H -N MR ( CD C l ) δ: 1. 10-1. 40 ( m, 3H ), 1.5 0-1. 80 (m , 1H ), 1.83- 2.24 ( m, 6H ), 2.68 (d, J = 6. 0 H z, 2H) , 3.06- 3.50 ( m, 3H ), 6. 70-6. 85 (m , 188 1H ), 7. 18-7. 35 (m, 1H ), 9. 10 (br s, 1H ), 9. 22 ( s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 1. 30 m in LC /M S (E SI ) m /z; 353 [ M+H ] H -N MR ( CD C l ) δ: 1. 11-1. 45 ( m, 3H ), 1.7 8-2. 36 (m , 6H ), 2.91- 3.31 ( m, 5H ), 3.00 (s , 3H) , 3. 52-3. 80 ( m, 2H ), 6.40 (d, J = 8. 6 Hz, 1H) , 6. 70-6. 90 (m , 1H) , 7.20- 7.38 (m, 1H ), 7. 50 (s, 1H ), 7. 54-7. 73 (m , 1H ), 9. 22 ( s, 1H ), 9. 30 ( br s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 2. 13 m in + + - - LC /M S (E SI ) m /z; 451 [ M+H ] , LC /M S( ES I ) m /z; 44 9 [ M-H ] H -N MR (C DC l ) δ: 1. 15-1 .40 (m , 3H ), 1.80- 2.30 (m , 6H ), 2.68 ( s, 6H ), 3. 00-3 .30 (m, 5H ) , 3.55- 3.74 (m , 2H) , 6. 40 ( d, J = 8.6 Hz, 1H) , 6. 79 ( t, J = 2. 4 H z, 1H ) , 7.29 (t , J = 3. 0 H z, 1H ), 7. 34 (s, 1 H) , 7.50 ( dd, J = 8. 3, 1.2 H z, 1H ), 9. 09 ( br s, 1H ), 9. 22 ( s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 2.35 m in + + - - LC /M S (E SI ) m /z; 480 [ M+H ] , LC /M S( ES I ) m /z; 47 8 [ M-H ] H -N MR ( CD C l ) δ: 1. 00-1. 40 ( m, 3H ), 1.5 0-2. 40 (m , 7H ), 2.51- 2.93 ( m, 4H ) , 3.00- 3.23 ( m, 1H) , 3. 25-3. 68 ( m, 6H) , 4. 50-4. 89 (m , 1H ), 6. 67-6. 84 ( m, 1H ), 7. 20-7. 42 ( m, 1H ), 9. 20 (s, 1H ), 9. 97 ( br s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 1. 13 m in LC /M S (E SI ) m /z; 383 [ M+H ] LC /M S (E SI ) m / z; 381 [ M- H] H -N MR (D MS O- d ) δ: 1. 13-1. 42 (m, 2H ), 1. 64-2. 15 (m , 6H) , 2. 78-3. 60 ( m, 9H ), 6. 81 ( s, 1H ), 7. 40-7. 62 ( m, 2H ) , 8.99 (s, 1H ) , 9. 08 ( br s, 1H ), 9. 52 ( s, 1H ), 12. 56 ( s, 1H) , 14. 44 ( br s , 1H) .

LC /M S : condi ti on 3, r etent ion t im e = 0. 68 m in LC /M S (E SI ) m /z; 365 [ M+H ] LC /M S (E SI ) m / z; 363 [ M- H] TABLE 122 E x D ata H -N MR ( D MS O- d ) δ: 1. 10-1 .26 (m , 2H) , 1.51- 1.63 (m , 1H) , 1.75 ( qd, J = 12.2, 3 .3 Hz, 2H ) , 1.92- 2.04 (m , 4H ), 2. 42 ( d, J = 6.6 H z, 2H ), 3. 13 ( tt , J = 12. 6, 3.3 Hz , 1H ), 3. 72 ( s, 2H ), 6. 80 ( d, J = 3.6 Hz, 1H ), 7.22 (t t, J = 6. 9, 2. 0 H z, 1H ), 7.28- 7.38 (m , 4H ), 7. 49 ( d, J = 3. 3 H z, 1H ), 9. 51 ( s, 1H ), 12. 52 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 2. 67 m in LC /M S (E SI ) m /z; 361 [M +H ] LC /M S (E SI ) m /z; 359 [ M- H] H -N MR (D MS O- d ) δ: 1. 55-1. 70 (m, 4H) , 1. 81-1. 92 ( m, 2H) , 1. 99-2. 07 (m, 1H ), 2. 20-2. 35 (m , 2H ), 2.84- 2.89 (m , 1H ), 3.16- 3.29 ( m, 1H ), 3.75 (s, 2H ), 7.13 (d, J = 3. 3 H z, 1H) , 7 .23 (tt , J = 6. 9, 1.7 H z, 1H ), 7. 31-7. 43 ( m, 5H ), 9. 50 (s, 1H ), 12. 49 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 2. 22 m in LC /M S (E SI ) m /z; 347 [M +H ] LC /M S (E SI ) m /z; 345 [ M- H] H -N MR ( DM SO -d ) δ: 1.26- 1.42 (m, 2H ), 1.75 (qd, J = 12. 7, 3. 3 H z, 2H ), 1.95- 2.14 (m , 5H ), 2.51- 2.62 ( m, 1H ) , 3.15 ( tt , J = 1 2.3, 3 .7 H z, 1H ), 3. 79 (s, 2H ), 6. 79 (d, J = 3. 3 H z, 1H ) , 7. 22 ( tt , J = 7. 4, 1.6 Hz, 194 1H ), 7. 28-7. 39 (m , 4H ), 7. 48 (d, J = 3.3 Hz, 1H ), 9.50 (s, 1H ), 12.51 b ( br s , 1H) .

LC /M S : condit i on 1, re tent ion ti m e = 1. 47 m in LC /M S (E SI ) m /z; 347 [M +H ] LC /M S (E SI ) m /z; 345 [ M- H] H -N MR (D MS O- d ) δ: 1. 54-1. 69 (m, 4H) , 1. 80-1. 90 ( m, 2H) , 2. 18-2. 33 (m, 2H ), 2. 81-2. 88 (m , 1H ), 3.14- 3.17 (m , 1H ), 3.18- 3.30 ( m, 1H ), 3.73 (s, 2H ), 7.08- 7.20 (m, 3H ), 7. 38-7. 46 (m , 3H ) , 9. 50 ( s, 1H ), 12. 49 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 2. 55 m in LC /M S (E SI ) m /z; 365 [M +H ] LC /M S (E SI ) m /z; 363 [ M- H] H -N MR (D MS O- d ) δ: 1. 25-1. 41 (m, 2H) , 1. 67-1. 83 ( m, 2H) , 1. 95-2. 12 (m , 5H) , 2.51- 2.60 ( m, 1H ), 3.0 8-3. 20 (m , 1 H) , 3. 78 ( s, 2H ), 6. 80 (d, J = 3.3 H z, 1H ), 7. 10-7. 18 ( m, 2H ), 7 .37-7 .44 (m, 2H ) , 7. 49 ( d, J = 3. 3 H z, 1H ) , 9.51 (s, 1H ) , 12.53 (br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 1. 03 m in LC /M S (E SI ) m /z; 365 [M +H ] LC /M S (E SI ) m /z; 363 [ M- H] H -N MR ( CD Cl ) δ: 1.77- 1.92 ( m, 6H ), 2.1 9 (m , 2 H) , 2. 81 (m , 1H ), 3. 00 (d, J = 1 3.2 H z, 1H ), 3.35 (m , 1H) , 3. 55 ( d, J = 13.2 H z, 1H ) , 6. 75 (d, J = 3. 3 H z, 1H ) , 7. 30 ( m, 1H ), 7.37 (m , 3H ), 7. 60 (m , 2H ) , 9. 22 ( s, 1H ), 9. 44 ( br s, 1H) .

LC /M S : condit i on 1, re tent ion ti m e = 2. 75 m in LC /M S (E SI ) m /z; 445 [M +H ] LC /M S (E SI ) m /z; 443 [ M- H] TABLE 123 E x D ata H -N MR ( CD Cl ) δ: 1.26- 1.38 ( m, 2H ), 1.9 2 (m , 2 H) , 2. 15 (m , 4H ), 2. 62 ( tt , J = 11. 4, 3.6 H z, 1H ) , 3.02 (d, J = 1 3.2 H z, 1H ), 3. 15 ( tt , J = 12 .0, 3.3 H z, 1H ), 3.6 0 ( d, J = 13.2 Hz, 1H ), 6. 74 (d, J = 3. 3 H z, 196 1H ), 7. 30 ( d, J = 2.7 H z, 1H ), 7. 39 ( m, 3H ), 7. 61 (m , 2H) , 9.22 (s , b 1H ), 9. 63 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 2. 57 m in LC /M S (E SI ) m /z; 445 [M +H ] LC /M S (E SI ) m /z; 443 [ M- H] H -N MR (D MS O- d ) δ: 1. 56-1. 71 (m, 4H) , 1. 80-1. 91 ( m, 2H) , 2. 13-2. 35 (m , 3H) , 2.82- 2.88 ( m, 1H ), 3.1 9-3. 30 (m , 1 H) , 3. 75 ( s, 2H ), 7. 10 (d, J = 3.3 Hz, 1H ), 7.39- 7.47 ( m, 5H ), 9.5 2 (s, 1H ), 12.51 ( br s , 1H) .

LC /M S : condit i on 1, re tent ion ti m e = 2. 75 m in LC /M S (E SI ) m /z; 381 [M +H ] LC /M S (E SI ) m /z; 379 [ M- H] H -N MR ( DM SO -d ) δ: 1.26- 1.41 (m, 2H ), 1.75 (qd, J = 12. 6, 2. 3 H z, 2H ), 1.95- 2.12 (m , 5H ), 2. 54 (t t, J = 10.9, 3.3 H z, 1H ), 3.14 (t t, J = 11. 9, 3. 3 H z, 1H ) , 3. 78 (s , 2H ), 6. 80 (d, J = 3.3 H z, 1H ), 7.34- 7.43 ( m, 4H ), 7. 49 ( d, J = 3 .0 Hz, 1H ), 9.51 (s, 1H ) , 12.53 (br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 2. 62 m in LC /M S (E SI ) m /z; 381 [M +H ] LC /M S (E SI ) m /z; 379 [ M- H] H -N MR (C D Cl ) δ : 1. 33 (m , 2H ), 1. 94 ( m, 2H ), 2.14 ( m, 4H ), 2.69 ( m, 1H) , 2. 83 (t , J = 6. 9 H z, 2H ), 2.99 (t, J = 6.9 H z, 2H) , 3.16 ( tt , J = 12.0, 3. 3 Hz, 1H ), 7. 75 (d, J = 3. 3 H z, 1H ), 7. 16 (m , 2H ) , 7. 29 (m , 3H ), 9. 21 ( s, 1H ), 9. 46 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 2. 87 m in LC /M S (E SI ) m /z; 395, 3 97 [ M+H ] LC /M S (E SI ) m /z; 393, 395 [ M- H] H -N MR ( CD Cl ) δ: 1.26- 1.38 ( m, 2H ), 1.9 2 (m , 2 H) , 2. 15 (m , 4H ), 2. 62 ( tt , J = 11. 1, 3.3 H z, 1H ) , 2.98 (d, J = 1 2.9 H z, 1H ), 3. 16 ( tt , J = 12 .6, 3.3 H z, 1H ), 3.6 0 ( d, J = 13.2 Hz, 1H ), 6. 74 (d, J = 3. 3 H z, 1H ), 7. 30-7. 39 ( m, 3H ), 7. 55 ( m, 2H ), 9.23 (s, 1H ), 9. 77 (br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 2. 97 m in LC /M S (E SI ) m /z; 479, 4 81 [ M+H ] LC /M S (E SI ) m /z; 477, 479 [ M- H] H -N MR ( CD Cl ) δ: 1.26- 1.43 ( m, 2H ), 1.9 2 (m , 2 H) , 2. 15 (m , 4H ), 2. 63 ( tt , J = 11. 4, 3.3 H z, 1H ) , 3.00 (d, J = 1 3.2 H z, 1H ), 3. 17 ( tt , J = 12 .3, 3.3 H z, 1H ), 3.6 0 ( d, J = 13.2 Hz, 1H ), 6. 74 (d, J = 3. 3 H z, 200 1H ), 7.09 (t , J = 8. 4 H z, 2H ) , 7.3 2 ( d, J = 3. 0 H z, 1H ) , 7.59( dd, J = b 8. 7, 5.7 H z, 2H) , 9.2 4 (s , 1H) , 10.00 (br s, 1H ) .

LC /M S : condit i on 1, re tent ion ti m e = 2. 79 m in LC /M S (E SI ) m /z; 463 [M +H ] LC /M S (E SI ) m /z; 461 [ M- H] TABLE 124 E x D ata H -N MR ( DM SO -d ) δ: 1.19- 1.35 (m, 2H ), 1.78 (qd, J = 12. 6, 4. 0 H z, 2H ), 1.9 2-2. 07 (m , 4H ), 2.51 -2.6 1 (m , 1H ) , 2. 68-2. 75 (m , 2H ) , 2. 78-2. 86 ( m, 2H ), 3. 07-3. 19 (m , 2H ), 6.80 (d, J = 3.6 H z, 1H ) , 201 7. 06-7. 14 ( m, 2H ), 7. 24-7. 31 ( m, 2H ), 7. 49 ( d, J = 3. 6 H z, 1H ) , 9.51 b ( s, 1H) , 12.5 2 (b r s , 1H) .

LC /M S : condit i on 1, re tent ion ti m e = 2. 57 m in LC /M S (E SI ) m /z; 379 [M +H ] LC /M S (E SI ) m /z; 377 [ M- H] H -N MR (C D O D) δ: 1.52 (m , 2H ), 1.90 (m , 2H ), 2. 18 ( m, 4H) , 2. 80-3. 00 (m , 3H) , 3. 23 ( m, 1H ), 4.92 (m , 1H ), 6. 82 (d, J = 3. 3 Hz , 202 1H ), 6. 83-7. 43 ( m, 6H ), 9. 29 ( s, 1H ). b LC /M S : condit i on 1, re tent ion ti m e = 0. 94 m in LC /M S (E SI ) m /z; 377 [M +H ] LC /M S (E SI ) m /z; 375 [ M- H] H -N MR ( CD OD ) δ: 1.43 (m , 2 H) , 1.90 ( m, 2H ), 2. 12 (m , 4H ), 2.71 ( tt , J = 11.1, 3.9 H z, 1H ), 2 .79-2 .91 (m , 2H) , 3. 21 (t t, J = 1 2.3, 3.6 H z, 1H ) , 4. 79 ( m, 1H ), 6.81 ( d, J = 3.3 Hz, 1H ), 7. 25-7. 42 (m , 6H ) , 9. 27 ( s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 1. 29 m in LC /M S (E SI ) m /z; 377 [M +H ] LC /M S (E SI ) m /z; 375 [ M- H] H -N MR (C D O D) δ: 1.57 (m , 2H ), 1.93 (m , 2H ), 2. 20 ( m, 4H) , 2. 95-3. 09 (m , 3H) , 3. 24 ( m, 1H ), 4.90 (m , 1H ), 6. 83 (d, J = 3. 3 Hz , 204 1H ), 7. 27-7. 44 ( m, 6H ), 9. 30 ( s, 1H ). b LC /M S : condit i on 1, re tent ion ti m e = 1. 29 m in LC /M S (E SI ) m /z; 377 [M +H ] LC /M S (E SI ) m /z; 375 [ M- H] LC /M S : c ondi t ion 1, r etent i on t im e = 3.80, 4. 15 mi n ( ci s/t rans mi xt ure) 205 + + LC /M S (E SI ) m /z; 367 [M +H ] LC /M S (E SI ) m /z; 365 [ M- H] H -N MR (D MS O- d ) δ: 1. 72-1. 88 (m, 4H) , 1. 96-2. 13 ( m, 4H) , 3. 19-3. 38 ( m, 2H ), 6. 89 ( d, J = 3. 3 H z, 1H ) , 7. 10-7 .18 ( m, 2H) , 7.51 ( d, J = 3.0 H z, 1H ), 7.63- 7.70 ( m, 2H) , 9. 54 (s , 1H ), 9.98 (s, 1H) , 206 12. 55 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 63 m in LC /M S (E SI ) m /z; 379 [M +H ] LC /M S (E SI ) m /z; 377 [ M- H] H -N MR (D MS O- d ) δ: 1. 66-1. 82 (m, 4H) , 1. 89-1. 97 ( m, 2H) , 2. 00-2. 09 ( m, 2H ) , 2.32- 2.43 (m , 1H ), 3. 14-3. 25 (m, 1H) , 4.27 (d , J = 6. 3 H z, 2H) , 6.86 (dd, J = 3.0, 1. 7 H z, 1H ), 7.12- 7.20 (m , 2H) , 7. 26-7. 32 (m , 2H ), 7. 50 (t , J = 3. 0 Hz , 1H ), 8.31- 8.37 (m , 1H ), 9.52 ( s, 1H) , 12.5 3 (b r s , 1H) .

LC /M S : condit i on 1, re tent ion ti m e = 3. 49 m in LC /M S (E SI ) m /z; 393 [M +H ] LC /M S (E SI ) m /z; 391 [ M- H] TABLE 125 E x D ata H -N MR (D MS O- d ) δ: 1. 60-1. 88 (m, 6H) , 1. 98-2. 06 ( m, 2H) , 2. 20-2. 31 (m, 1H) , 2. 72 ( t, J = 6. 9 Hz, 2 H) , 3. 11-3. 22 ( m, 1H) , 3. 24-3. 31 (m , 2H ), 6.84 ( dd, J = 3. 0, 1. 7 Hz, 1H ), 7.07- 7.16 ( m, 2H) , 7. 21-7. 28 (m , 2H) , 7.50 (t, J = 3.0 H z, 1H ), 7. 85 (t , J = 5. 6 H z, 1H ) , 9. 52 ( s, 1H ), 12. 53 ( br s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 3. 59 m in LC /M S (E SI ) m /z; 407 [M +H ] LC /M S (E SI ) m /z; 405 [ M- H] LC /M S : condit i on 1, re tent ion ti m e = 3. 00 m in 209 LC /M S (E SI ) m /z; 357 [M +H ] LC /M S (E SI ) m /z; 355 [ M- H] H -N MR (D M SO -d ) δ: 1. 78-1. 98 (m , 3H) , 2. 21 ( br s, 1H ), 2.91 (br s , 3H ), 3. 63 (s, 2H ), 6. 57 ( s, 1H ) , 7. 17 ( s, 1H) , 7.57 ( d, J = 7.5 Hz, 2H ), 7.82 ( d, J = 7. 5 Hz, 2H ), 8. 31 (s, 1H ), 8. 83 (s, 1H ), 11. 94 (br s , 1H ).

LC /M S : condit i on 3, re tent ion ti m e = 1. 21 m in LC /M S (E SI ) m /z; 357 [M +H ] H -N MR (C DC l ) δ: 2. 46-2. 63 (m , 2H ), 3.58- 4.09 (m , 5H ), 5.18 (s , 2H ), 6. 76 ( s, 1H ), 7. 31-7. 40 ( m, 6H ), 9. 19 ( br s, 1H ), 9. 24 ( s, 1H ). 211 LC /M S : condit i on 3, re tent ion ti m e = 2. 05 m in LC /M S (E SI ) m /z; 363 [M +H ] LC /M S (E SI ) m /z; 361 [ M- H] H -N MR (C DC l ) δ: 2.02- 2.41 ( m, 5H) , 2. 45-2. 73 (m , 3H ), 3.02 ( d, J = 10.7 H z, 1H) , 3.21- 3.36 (m , 1H) , 3.37 (d, J = 9.4 Hz, 1H) , 4.86 ( dd, J = 10.7, 3.4 H z, 1H) , 6. 82 ( d, J = 3.0 Hz, 1H ), 7. 32 ( br s, 1H ), 7. 54 (d, J = 8 .3 H z, 2H ), 7. 63 (d , J = 8.3 H z, 2H ) , 9. 14 ( br s, 1H) , 9. 25 ( s, 1H ).

LC /M S : condit i on 1, re tent ion ti m e = 2. 67 m in LC /M S (E SI ) m /z; 431 [M +H ] LC /M S (E SI ) m /z; 429 [ M- H] TABLE 126 Ex Data LC /M S: co ndi tion 3, ret enti on time = 1.35 mi n 21 3 LC /M S(ESI ) m /z; 388 [M+ H ] LC /M S(ESI ) m/z ; 38 6 [M - H] H - NMR (D MSO - d ) δ: 1.8 6- 2 .05 ( m , 4H ), 2 .19 -2.3 2 (m, 2H ) , 2 .8 8- 3.0 0 (m , 2H ) , 3. 37 - 3.5 0 ( m , 1H ), 3. 60 (s , 2 H ), 6. 80 -6. 85 ( m, 1 H ), 7 .4 7 -7. 54 (m , 2 H ), 7 .8 0 - 7 .8 9 (m , 1 H ) , 8 . 38 - 8 .4 2 ( m , 1 H) , 21 4 9.5 3 (s , 1 H), 12. 54 (br s , 1 H) .

LC /M S: co ndi tion 3, ret enti on time = 1.21 mi n LC /M S(ESI ) m /z; 368 [M+ H ] LC /M S(ESI ) m/z ; 36 6 [M - H] H - NMR ( DM SO-d ) δ: 1.88 -2.08 (m , 4 H), 2. 13- 2. 29 (m , 2H ), 2.9 4-3.0 7 (m , 2H) , 3.10 -3.22 (m, 3H ), 6 .10- 6 .22 (m , 1 H ), 6.3 7-6.5 3 (m, 3H ), 6.8 1 (d, J = 3 .2 Hz, 1H ) , 7.49 ( d, J = 3 .2 Hz , 1H ), 7.60 (s , 21 5 1H ), 9 .52 (s , 1H ) , 12.5 2 ( br s , 1H) .

LC /M S: co ndi tion 3, ret enti on time = 1.40 mi n LC /M S(ESI ) m /z; 349 [M+ H ] H - NMR (D MSO - d ) δ : 1 .84 -2.05 (m , 4H ) , 2.0 5-2.1 8 (m, 2H ), 2.2 4 (s, 3H ), 2.86 -2.96 (m , 2H) , 3.1 5-3.1 8 ( m , 1 H), 6.8 0 (d , J = 3 .2 Hz , 21 6 1H ), 7 .49 (d , J = 3 .2 H z , 1H ), 9 .52 (s , 1 H), 12.5 3 ( b r s, 1 H).

LC /M S: co ndi tion 3, ret enti on time = 0.47 mi n LC /M S(ESI ) m /z; 257 [M+ H ] H - NMR ( DM SO-d ) δ: 1.85 -2.06 (m , 4 H), 2. 18- 2. 32 (m , 2H ), 2.7 0-2.7 6 (m, 1H) , 2.9 0-3. 03 ( m, 2 H), 3. 68 (s, 2 H ), 6 .82 (d, J = 3. 3 H z, 1 H ), 7.45 - 7.6 2 (m , 4H) , 9 .52 (s , 1 H ), 12.5 3 (b r s, 1H ), 1 3.22 (br 21 7 s, 1H ).

LC /M S: co ndi tion 3, ret enti on time = 1.35 mi n LC /M S(ESI ) m /z; 407 , 40 9 [M +H ] H - NMR ( DM SO-d ) δ: 1.88 -2.15 (m , 4 H), 2. 25- 2. 40 (m , 2H ), 2.9 7-3.1 0 (m, 2H) , 3.1 4-3. 30 ( m, 1 H), 3. 83 (s, 2 H ), 6 .84 (d, J = 3. 0 H z, 1H ), 7 .50 (d , J = 3.0 H z, 1 H), 7 .89 - 7.96 (m, 1 H) , 8 .00 -8 .15 (m , 21 8 2H ), 8 .89-9 .00 (m , 2H ), 9 .52 (s, 1 H), 12.5 3 (br s, 1 H).

LC /M S: co ndi tion 3, ret enti on time = 1.15 mi n LC /M S(ESI ) m /z; 385 [M+ H ] H - NMR ( DM SO-d ) δ: 1.82 -2.08 (m , 4 H), 2. 20- 2. 32 (m , 2H ), 2.9 4-3.1 0 (m, 2H) , 3.1 0-3. 23 ( m, 1 H), 3. 50 (s, 2 H ), 6 .80 (d, J = 3. 2 H z, 1H ), 7.4 8 ( d , J = 3 .2 H z, 1H) , 8.01 (s, 1H ), 8.3 1 (s, 1H ), 9.5 2 21 9 (s, 1H ) , 12 .53 ( b r s, 1H) .

LC /M S: co ndi tion 3, ret enti on time = 0.63 mi n LC /M S(ESI ) m /z; 324 [M+ H ] H - NMR (D MSO - d ) δ : 1 .93 -2.00 (m , 4H ) , 2.1 6-2.2 2 (m, 2H ), 2.9 3 (d, J = 11 .4 H z , 2 H ), 3. 16 (s, 1H ), 3.53 (s , 2 H), 6.7 8 (d d, J = 3.3 , 1.2 , 1H ) , 7.13 ( d, J = 8.4 H z, 2H ), 7. 20 (s, 1 H ), 7.3 9 ( d , J = 7 .8 H z , 22 0 2H ), 7 .45-7 .47 (m , 1H ), 9 .48 (s, 1 H).

LC /M S: co ndi tion 3, ret enti on time = 1.54 mi n LC /M S(ESI ) m /z; 399 [M+ H ] TABLE 127 Ex Data H - NMR (D MSO - d ) δ: 1 .95-2 .06 ( m , 4 H ), 2 .23 (t, J = 9.8 H z, 2H ), 2.9 7 (d, J = 10 .8 H z, 2 H ), 3 .16 (s , 1H ), 3.5 9 ( s, 2 H) , 6 .80 (d , J = 3.3 H z, 1 H) , 7.08 (s, 1 H ), 7.47 - 7.49 (m, 3 H ), 7.61 (d, J = 8.4 Hz , 22 1 2H ), 7 .72 (s , 1H ) , 8.22 ( s, 1 H) , 9.4 9 (s, 1H ).

LC /M S: co ndi tion 3, ret enti on time = 0.48 mi n LC /M S(ESI ) m /z; 399 [M+ H ] H - NMR (D MSO - d ) δ: 1.9 2- 2 .09 ( m , 4H ), 2 .25 -2.3 2 (m, 2H ) , 2 .9 4 ( d , J = 11 .1 H z, 2H ) , 3 .68 (s , 2H) , 6. 82 (d , J = 2.7 Hz , 1H ), 7 .43-7 .54 (m, 3H ), 7 .91 (t, J = 7.5 H z, 1H ), 9 .50 (s, 1H) . 22 2 LC /M S: co ndi tion 3, ret enti on time = 1.35 mi n LC /M S(ESI ) m /z; 376 [M+ H ] LC /M S(ESI ) m/z ; 37 4 [M - H] H - NMR ( DM SO-d ) δ: 1.9 3- 2.0 5 (m , 4 H) , 2.24 ( td, J = 11. 1, 3 .3 H z , 2H ), 2 .92 (d, J = 11.7 H z, 2 H) , 3.58 ( s , 2H ), 6 .81 (d , J = 2.7 Hz , 1H ), 7.4 7- 7.5 3 ( m, 2H ), 7.75 - 7.8 0 (m , 1H ), 7.86 (d d, J = 6 .3, 2. 1 22 3 H z, 1 H ), 9.51 (s, 1H ), 12 .51 (b r s, 1H ).

LC /M S: co ndi tion 3, ret enti on time = 1.37 mi n LC /M S(ESI ) m /z; 376 [M+ H ] LC /M S(ESI ) m/z ; 37 4 [M - H] LC /M S: co ndi tion 3, ret enti on time = 1.63 mi n 22 4 LC /M S(ESI ) m /z; 437 [M+ H ] LC /M S(ESI ) m/z ; 43 5 [M - H] H - NMR ( DM SO-d ) δ: 1.89 -2.08 (m , 4 H), 2. 11- 2. 32 (m , 2H ), 2.8 9-3.0 3 (m, 2H ), 3.1 2-3.2 6 (m , 1H ), 3.40 -3.5 2 (m , 2H ), 4.55 (s , 2H ), 6. 77-7 .00 (m , 4H ), 7.4 7-7.5 3 (m, 1 H ) , 9.52 (s, 1 H), 1 0.66 (br 22 5 s, 1H ), 12 .53 (b r s, 1H ).

LC /M S: co ndi tion 3, ret enti on time = 1.23 mi n LC /M S(ESI ) m /z; 404 [M+ H ] LC /M S(ESI ) m/z ; 40 2 [M - H] H - NMR ( DMSO -d ) δ : 1.90 - 1.9 7 ( m, 4H ), 2. 13 (t, J = 1 0.7 H z , 2H ), 2.6 9 (t, J = 6.6 H z, 2 H ), 2.9 1- 2.9 6 ( m, 5 H ), 3.4 1 (s , 2H ), 3.6 4 (t, J = 6.8 H z, 2H) , 6.7 3 ( d, J = 8 .4 H z, 2 H) , 6 .79 (d , J = 3.3 H z , 1H ), 22 6 7.1 5 (d, J = 8.1 H z, 2H ), 7.4 8 (d , J = 3. 0 H z, 1H ), 9.5 0 (s , 1H ).

LC /M S: co ndi tion 3, ret enti on time = 1.48 mi n LC /M S(ESI ) m /z; 415 [M+ H ] H - NMR ( DM SO-d ) δ: 1.87 -2.08 (m , 4 H), 2. 15- 2. 30 (m , 2H ), 2.9 0-3.0 0 (m, 2H) , 3.1 0-3. 26 ( m, 1 H), 3. 57 (s, 2 H ), 6 .82 (d, J = 3. 3 H z, 1 H), 7 .19 ( dd, J = 1.5 , 8.5 Hz , 1H ) , 7 .36 (d, J = 8 .5 H z, 1H ), 7.3 9 (d, J = 1.5 H z, 1 H ) , 7 .49 (d , J = 3.3 H z, 1 H ) , 9 .52 (s , 1H ), 22 7 12 .52 (b r s, 1H ).

LC /M S: co ndi tion 3, ret enti on time = 1.66 mi n LC /M S(ESI ) m /z; 413 [M+ H ] LC /M S(ESI ) m/z ; 41 1 [M - H] TABLE 128 Ex Data H - NMR ( DM SO-d ) δ: 1.87 -2.08 (m , 4 H), 2. 18- 2. 32 (m , 2H ), 2.9 0-3.0 3 (m, 2H ), 3.0 4-3.2 2 (m , 1H ), 3.55 (s , 2H ), 6.39 -6.48 ( m , 2H ), 6 .81 (d , J = 3.0 Hz , 1H ), 7 .48 (d, J = 3.0 H z, 1 H), 9.5 1 (s , 1H ), 22 8 12 .52 (b r s, 1H ).

LC /M S: co ndi tion 3, ret enti on time = 1.37 mi n LC /M S(ESI ) m /z; 357 , 35 9 [M +H ] H - NMR (D MSO - d ) δ: 1.8 6- 2 .06 ( m , 4H ), 2 .20 -2.3 4 (m, 2H ) , 2 .9 2- 3.0 2 (m , 2H ) , 3. 10 - 3.2 4 ( m , 1H ), 3. 67 (s , 2 H ), 6. 80 -6. 85 ( m, 1H ) , 7.1 4- 7 .3 3 (m , 3H) , 7 .44 -7 .50 ( m, 1 H ), 9. 52 (s , 1H ), 12 .52 22 9 (br s , 1H) .

LC /M S: co ndi tion 3, ret enti on time = 1.60 mi n LC /M S(ESI ) m /z; 413 [M+ H ] LC /M S(ESI ) m/z ; 41 1 [M - H] H - NMR ( DM SO-d ) δ: 1.94 -2.17 (m , 4 H), 3. 46- 3. 65 (m , 3H ), 4.2 5-4.3 8 (m, 2 H), 6 .91 (d , J = 3 .3 H z, 1H ), 7.1 0 (t, J = 6. 9 H z, 1H ), 7.31 (t, J = 6.9 H z, 2H ), 7 .51 (d, J = 7.5 H z, 2H ), 7 .52 (s, 2H ), 23 0 9.5 4 (s , 1H ) , 12 .56 ( br s , 1H ) .

LC /M S: co ndi tion 3, ret enti on time = 2.23 mi n LC /M S(ESI ) m /z; 370 [M+ H ] LC /M S(ESI ) m/z ; 36 8 [M - H] LC /M S: co ndi tion 3, ret enti on time = 1.44 mi n 23 1 LC /M S(ESI ) m /z; 402 , 40 4 [M +H ] LC /M S(ESI ) m/z ; 40 0, 4 03 [ M- H] LC /M S: co ndi tion 3, ret enti on time = 1.49 mi n 23 2 LC /M S(ESI ) m /z; 390 [M+ H ] LC /M S(ESI ) m/z ; 38 8 [M - H] LC /M S: co ndi tion 3, ret enti on time = 1.77 mi n 23 3 LC /M S(ESI ) m /z; 495 , 49 7, 49 9 [M +H ] LC /M S(ESI ) m/z ; 49 3, 4 95, 497 [M- H] LC /M S: co ndi tion 3, ret enti on time = 1.20 mi n 23 4 LC /M S(ESI ) m /z; 425 [M+ H ] LC /M S(ESI ) m/z ; 42 3 [M - H] LC /M S: co ndi tion 3, ret enti on time = 2.44 mi n 23 5 LC /M S(ESI ) m /z; 404 , 40 6 [M +H ] LC /M S(ESI ) m/z ; 40 2, 4 04 [ M- H] LC /M S: co ndi tion 3, ret enti on time = 1.46 mi n 23 6 LC /M S(ESI ) m /z; 353 [M+ H ] LC /M S(ESI ) m/z ; 35 1 [M - H] LC /M S: co ndi tion 3, ret enti on time = 1.51 mi n 23 7 LC /M S(ESI ) m /z; 417 , 41 9 [M +H ] LC /M S: co ndi tion 3, ret enti on time = 1.55 mi n 23 8 LC /M S(ESI ) m /z; 417 , 41 9 [M +H ] LC /M S(ESI ) m/z ; 41 5, 4 17 [ M- H] LC /M S: co ndi tion 3, ret enti on time = 0.50 mi n 23 9 LC /M S(ESI ) m /z; 334 [M+ H ] LC /M S(ESI ) m/z ; 33 2 [M - H] TABLE 129 Ex Data H - NMR ( DM SO-d ) δ: 1.85 -2.08 (m , 4 H), 2. 20- 2. 34 (m , 2H ), 2.9 6-3.0 9 (m, 2H) , 3.0 9-3. 22 ( m, 1 H), 3. 74 (s, 2 H ), 6 .81 (d, J = 3. 2 H z, 1H ), 7.4 8 ( d , J = 3 .2 H z, 1H) , 7.55 (s, 1H ), 9.0 6 (s, 1H ), 9.5 2 24 0 (s, 1H ) , 12 .52 ( b r s, 1H) .

LC /M S: co ndi tion 3, ret enti on time = 0.88 mi n LC /M S(ESI ) m /z; 340 [M+ H ] H- NM R (D MS O- d ) δ: 1 .95- 2 .08 ( m , 4H ), 2.2 2 (t, J = 1 1.1 H z, 2 H ), 2 .9 5 ( d , J = 9 .9 H z , 2 H ), 3 .2 8 ( s , 1 H ), 3. 60 ( s , 2H ) , 6. 82 (br s, 1H) , 7.2 8 (b r s , 1 H ), 7 .42 (d, J = 8 .1 H z, 2H ), 7.4 9 ( t , J = 2.7 H z , 1 H ), 7.8 4 (d, J = 8 .1 H z, 2H ) , 7 .91 (b r s , 1H ) , 9.5 1 24 1 ( s , 1 H), 12 .52 (br s , 1 H ).

LC /M S: co ndi tion 3, ret enti on time = 0.73 mi n LC /M S(ESI ) m /z; 376 [M+ H ] LC /M S(ESI ) m/z ; 37 4 [M - H] H - NMR ( DMSO -d ) δ : 1.95 - 2.0 4 ( m, 4H ), 2. 28 (t, J = 1 0.1 H z , 2H ), 2.9 2 (d , J = 11.7 H z, 2 H ), 3.1 6- 3. 19 (m , 1H) , 3.70 ( s, 2H ), 6.8 2 (d d, J = 3 .3, 1 .5 H z, 1H) , 7 .49 ( d , J = 3.3 H z, 1H ), 7 .92 ( d, J = 8.7 H z, 24 2 1H ), 8 .11-8 .13 (m , 2H ), 9 .51 (s, 1 H).

LC /M S: co ndi tion 3, ret enti on time = 1.34 mi n LC /M S(ESI ) m /z; 383 [M+ H ] LC /M S(ESI ) m/z ; 38 1 [M - H] H - NMR ( DMSO -d ) δ : 1.95 - 2.0 7 ( m, 4H ), 2. 28 (t, J = 1 0.1 H z , 2H ), 2.9 4 (d, J = 1 1.1 H z, 2 H ), 3 .71 (s , 2 H ), 6 .83 (dd , J = 3 .3, 1.2 H z , 1H ), 7.4 9 (d, J = 3.3 H z, 1 H ), 7 .97 (m , 2 H ), 8.13 (s , 1H ), 9.52 (s , 24 3 1H ).

LC /M S: co ndi tion 3, ret enti on time = 1.65 mi n LC /M S(ESI ) m /z; 426 [M+ H ] LC /M S(ESI ) m/z ; 42 4 [M - H] H - NMR ( DM SO-d ) δ: 1.9 1- 2.0 8 (m , 4 H) , 2.30 ( td, J = 11. 3, 2 .9 H z , 2H ), 2 .93 ( d, J = 11.7 H z, 2H ), 3 .16-3 .23 (m, 1H) , 3 .74 (s, 2H ), 6.8 2 (d, J = 3 .3 Hz , 1H ), 7 .48 (d , J = 3.3 H z, 1 H ), 7.8 9 ( d, J = 7 .8 H z, 1 H ), 7.98 (s, 1H ), 8.1 4 (d, J = 7 .8 H z, 1H ), 9.5 0 (s , 1H ). 24 4 LC /M S: co ndi tion 3, ret enti on time = 1.60 mi n LC /M S(ESI ) m /z; 426 [M+ H ] LC /M S(ESI ) m/z ; 42 4 [M - H] H - NMR (DM SO-d ) δ : 1 .35 ( d, J = 6.6 H z, 3H) , 1 .82-2 .05 ( m, 4H ), 2.0 5-2.3 0 (m, 2 H) , 2.83 -2.9 5 ( m, 1 H), 3 .02 - 3.19 (m , 1H) , 3 .55 ( q , J = 6.6 H z, 1H ) , 6.7 9 ( d , J = 8 .3 H z, 2 H ), 7. 18-7 .28 (m, 1H ), 7.2 8-7.4 0 (m, 4 H), 7.48 ( d, J = 3.3 Hz , 1H ), 9. 51 (s, 1 H ), 12.5 1 (br 24 5 s, 1H ).

LC /M S: co ndi tion 3, ret enti on time = 1.44 mi n LC /M S(ESI ) m /z; 347 [M+ H ] LC /M S(ESI ) m/z ; 34 5 [M - H] LC /M S: co ndi tion 3, ret enti on time = 1.16 mi n 24 6 LC /M S(ESI ) m /z; 282 [M+ H ] LC /M S(ESI ) m/z ; 28 0 [M - H] TABLE 130 E x D ata LC /M S : condi ti on 3, r etent ion t im e = 2. 38 m in 247 LC /M S (E SI ) m /z; 406 [ M+H ] LC /M S (E SI ) m / z; 404 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 2. 48 m in 248 LC /M S (E SI ) m /z; 422 [ M+H ] LC /M S (E SI ) m / z; 420 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 2. 48 m in 249 LC /M S (E SI ) m /z; 383 [ M+H ] LC /M S (E SI ) m / z; 381 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 2. 61 m in LC /M S (E SI ) m /z; 401 [ M+H ] LC /M S (E SI ) m / z; 399 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 2. 67 m in 251 LC /M S (E SI ) m /z; 433 [ M+H ] LC /M S (E SI ) m / z; 431 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 2. 36 m in 252 LC /M S (E SI ) m /z; 390 [ M+H ] LC /M S (E SI ) m / z; 388 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 0. 65 m in 253 LC /M S (E SI ) m /z; 371 [ M+H ] LC /M S (E SI ) m / z; 369 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 1. 24 m in 254 + + LC /M S (E SI ) m /z; 343 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 18 m in 255 LC /M S (E SI ) m /z; 335 [ M+H ] LC /M S (E SI ) m / z; 333 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 1. 40 m in 256 LC /M S (E SI ) m /z; 367 [ M+H ] LC /M S (E SI ) m / z; 365 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 1. 08 m in LC /M S (E SI ) m /z; 327 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 48 m in 258 LC /M S (E SI ) m /z; 407 [ M+H ] LC /M S (E SI ) m / z; 405 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 1. 16 m in 259 LC /M S (E SI ) m /z; 310 [ M+H ] LC /M S (E SI ) m / z; 308 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 0. 96 m in 260 LC /M S (E SI ) m /z; 354 [ M+H ] LC /M S (E SI ) m / z; 352 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 1. 09 m in LC /M S (E SI ) m /z; 382 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 2. 22 m in 262 LC /M S (E SI ) m /z; 397 [ M+H ] LC /M S (E SI ) m / z; 395 [ M- H] TABLE 131 E x D ata LC /M S : condi ti on 3, r etent ion t im e = 2. 49 m in 263 LC /M S (E SI ) m /z; 406 [ M+H ] LC /M S (E SI ) m / z; 404 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 2. 06 m in 264 LC /M S (E SI ) m /z; 386 [ M+H ] LC /M S (E SI ) m / z; 384 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 1. 17 m in LC /M S (E SI ) m /z; 355 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 17 m in LC /M S (E SI ) m /z; 355 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 10 m in LC /M S (E SI ) m /z; 341 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 51 m in LC /M S (E SI ) m /z; 405 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 51 m in 269 LC /M S (E SI ) m /z; 413 [ M+H ] LC /M S (E SI ) m / z; 411 [ M- H] H -N MR (C D O D ) δ: 1.34 (m , 2H ), 1. 84-2. 18 (m , 7H) , 2.9 6 (d , J = 6. 9 H z, 2H) , 3.23 (m, 1H ), 3. 82 (s , 3H ), 4. 17 (s , 2H ) , 6. 81 ( d, J = 3. 3 H z, 1H ) , 7. 01(d, J = 8. 7 H z, 2H ) , 7. 40 ( d, J = 3.3 H z, 1H ), 7.44 270 ( d, J = 8. 7 H z, 2H ) 9.30 (s , 1H) .

LC /M S : condi ti on 1, r etent ion t im e = 2. 72 m in LC /M S (E SI ) m /z; 391 [ M+H ] LC /M S (E SI ) m / z; 389 [ M- H] LC /M S : condi ti on 1, r etent ion t im e = 0. 37 m in 271 LC /M S (E SI ) m /z; 355 [ M+H ] LC /M S (E SI ) m / z; 353 [ M- H] LC /M S : condi ti on 1, r etent ion t im e = 1. 40 m in 272 LC /M S (E SI ) m /z; 315 [ M+H ] LC /M S (E SI ) m / z; 313 [ M- H] LC /M S : condi ti on 1, r etent ion t im e = 3. 12 m in 273 LC /M S (E SI ) m /z; 418 [ M+H ] LC /M S (E SI ) m / z; 416 [ M- H] LC /M S : condi ti on 1, r etent ion t im e = 3. 05 m in 274 LC /M S (E SI ) m /z; 418 [ M+H ] LC /M S (E SI ) m / z; 416 [ M- H] LC /M S : condi ti on 1, r etent ion t im e = 4. 40 m in 275 LC /M S (E SI ) m /z; 427 [ M+H ] LC /M S (E SI ) m / z; 425 [ M- H] LC /M S : condi ti on 1, r etent ion t im e = 2. 59 m in 276 LC /M S (E SI ) m /z; 391 [ M+H ] LC /M S (E SI ) m / z; 389 [ M- H] LC /M S : condi ti on 1, r etent ion t im e = 2. 52 m in 277 LC /M S (E SI ) m /z; 391 [ M+H ] LC /M S (E SI ) m / z; 389 [ M- H] TABLE 132 E x D ata LC /M S : condi ti on 1, r etent ion t im e = 0. 37 m in 278 LC /M S (E SI ) m /z; 355 [ M+H ] LC /M S (E SI ) m / z; 353 [ M- H] LC /M S : condi ti on 1, r etent ion t im e = 0. 39 m in 279 LC /M S (E SI ) m /z; 355 [ M+H ] LC /M S (E SI ) m / z; 353 [ M- H] LC /M S : condi ti on 1, r etent ion t im e = 0. 63 m in 280 LC /M S (E SI ) m /z; 311 [ M+H ] LC /M S (E SI ) m / z; 309 [ M- H] LC /M S : condi ti on 1, r etent ion t im e = 0. 39 m in LC /M S (E SI ) m /z; 336 [ M+H ] LC /M S (E SI ) m / z; 334 [ M- H] LC /M S : condi ti on 1, r etent ion t im e = 2. 70 m in 282 LC /M S (E SI ) m /z; 400 [ M+H ] LC /M S (E SI ) m / z; 398 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 1. 36 m in LC /M S (E SI ) m /z; 325 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 46 m in LC /M S (E SI ) m /z; 339 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 36 m in LC /M S (E SI ) m /z; 325 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 15 m in LC /M S (E SI ) m /z; 311 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 22 m in LC /M S (E SI ) m /z; 325 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 07 m in 288 LC /M S (E SI ) m /z; 356 [ M+H ] LC /M S (E SI ) m / z; 354 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 1. 33 m in LC /M S (E SI ) m /z; 355 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 49 m in LC /M S (E SI ) m /z; 339 [ M+H ] LC /M S (E SI ) m / z; 337 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 1. 39 m in 291 LC /M S (E SI ) m /z; 325 [ M+H ] LC /M S (E SI ) m / z; 323 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 2. 33 m in 292 LC /M S (E SI ) m /z; 379 [ M+H ] LC /M S (E SI ) m / z; 377 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 1. 37 m in 293 LC /M S (E SI ) m /z; 355 [ M+H ] LC /M S (E SI ) m / z; 353 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 1. 09 m in 294 LC /M S (E SI ) m /z; 327 [ M+H ] LC /M S (E SI ) m / z; 325 [ M- H] TABLE 133 E x D ata LC /M S : condi ti on 3, r etent ion t im e = 1. 36 m in LC /M S (E SI ) m /z; 325 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 10 m in LC /M S (E SI ) m /z; 299 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 07 m in LC /M S (E SI ) m /z; 329 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 03 m in 298 + + LC /M S (E SI ) m /z; 359 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 62 m in LC /M S (E SI ) m /z; 440 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 2. 38 m in 300 LC /M S (E SI ) m /z; 400 [ M+H ] LC /M S (E SI ) m / z; 398 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 1. 16 m in 301 + + LC /M S (E SI ) m /z; 350 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 14 m in 302 LC /M S (E SI ) m /z; 338 [ M+H ] LC /M S (E SI ) m / z; 336 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 1. 31 m in LC /M S (E SI ) m /z; 421 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 45 m in LC /M S (E SI ) m /z; 421 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 20 m in LC /M S (E SI ) m /z; 369 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 54 m in LC /M S (E SI ) m /z; 397 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 62 m in LC /M S (E SI ) m /z; 440 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 74 m in 308 LC /M S (E SI ) m /z; 437 [ M+H ] LC /M S (E SI ) m / z; 435 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 2. 00 m in 309 LC /M S (E SI ) m /z; 533 [ M+H ] LC /M S (E SI ) m / z; 531 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 1. 71 m in LC /M S (E SI ) m /z; 440 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 30 m in LC /M S (E SI ) m /z; 397 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 46 m in LC /M S (E SI ) m /z; 383 [ M+H ] LC /M S (E SI ) m / z; 381 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 1. 46 m in LC /M S (E SI ) m /z; 383 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 23 m in LC /M S (E SI ) m /z; 393 [ M+H ] TABLE 134 E x D ata LC /M S : condi ti on 3, r etent ion t im e = 0. 96 m in LC /M S (E SI ) m /z; 384 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 41 m in LC /M S (E SI ) m /z; 337 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 2. 52 m in 317 LC /M S (E SI ) m /z; 421 [ M+H ] LC /M S (E SI ) m / z; 419 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 1. 13 m in LC /M S (E SI ) m /z; 382 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 13 m in LC /M S (E SI ) m /z; 382 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 41 m in 320 LC /M S (E SI ) m /z; 436 [ M+H ] LC /M S (E SI ) m / z; 434 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 1. 41 m in 321 LC /M S (E SI ) m /z; 436 [ M+H ] LC /M S (E SI ) m / z; 434 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 1. 60 m in 322 LC /M S (E SI ) m /z; 421 [ M+H ] LC /M S (E SI ) m / z; 419 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 1. 76 m in LC /M S (E SI ) m /z; 405 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 83 m in LC /M S (E SI ) m /z; 419 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 23 m in LC /M S (E SI ) m /z; 343 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 38 m in LC /M S (E SI ) m /z; 387 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 19 m in LC /M S (E SI ) m /z; 341 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 26 m in 328 LC /M S (E SI ) m /z; 361 [ M+H ] LC /M S (E SI ) m / z; 359 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 1. 08 m in 329 LC /M S (E SI ) m /z; 285 [ M+H ] LC /M S (E SI ) m / z; 283 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 1. 18 m in LC /M S (E SI ) m /z; 299 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 28 m in LC /M S (E SI ) m /z; 313 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 38 m in LC /M S (E SI ) m /z; 327 [ M+H ] LC /M S : condi ti on 3, r etent ion t im e = 1. 21 m in LC /M S (E SI ) m /z; 309 [ M+H ] LC /M S : condi ti on 1, r etent ion t im e = 0. 34 m in 334 LC /M S (E SI ) m /z; 424 [ M+H ] LC /M S (E SI ) m / z; 422 [ M- H] TABLE 135 Ex Data LC /M S: co ndi tion 1, ret enti on time = 2.94 mi n 33 5 LC /M S(ESI ) m /z; 468 [M+ H ] LC /M S(ESI ) m/z ; 46 6 [M - H] LC /M S: co ndi tion 1, ret enti on time = 2.75 mi n 33 6 LC /M S(ESI ) m /z; 468 [M+ H ] LC /M S(ESI ) m/z ; 46 6 [M - H] LC /M S: co ndi tion 1, ret enti on time = 2.77 mi n 33 7 LC /M S(ESI ) m /z; 440 [M+ H ] LC /M S(ESI ) m/z ; 43 8 [M - H] LC /M S: co ndi tion 3, ret enti on time = 1.15 mi n 33 8 LC /M S(ESI ) m /z; 329 [M+ H ] LC /M S(ESI ) m/z ; 32 7 [M - H] LC /M S: co ndi tion 3, ret enti on time = 1.19 mi n 33 9 LC /M S(ESI ) m /z; 347 [M+ H ] LC /M S(ESI ) m/z ; 34 5 [M - H] LC /M S: co ndi tion 3, ret enti on time = 0.81 mi n 34 0 LC /M S(ESI ) m /z; 368 [M+ H ] LC /M S: co ndi tion 3, ret enti on time = 1.39 mi n 34 1 LC /M S(ESI ) m /z; 410 [M+ H ] LC /M S(ESI ) m/z ; 40 8 [M - H] LC /M S: co ndi tion 3, ret enti on time = 1.85 mi n 34 2 LC /M S(ESI ) m /z; 403 [M+ H ] LC /M S(ESI ) m/z ; 40 1 [M - H] LC /M S: co ndi tion 3, ret enti on time = 1.38 mi n 34 3 LC /M S(ESI ) m /z; 383 [M+ H ] LC /M S(ESI ) m/z ; 38 1 [M - H] LC /M S: co ndi tion 3, ret enti on time = 1.31 mi n 34 4 LC /M S(ESI ) m /z; 343 [M+ H ] LC /M S(ESI ) m/z ; 34 1 [M - H] LC /M S: co ndi tion 3, ret enti on time = 1.31 mi n 34 5 LC /M S(ESI ) m /z; 432 [M+ H ] LC /M S(ESI ) m/z ; 43 0 [M - H] H - NMR (C D O D ) δ: 1.3 9-1.7 4 (m, 6 H ) , 1 .95 (m , 2H ), 2 .19 ( tt, J = 11 .7, 3.3, 1H ) , 3.05 (tt, J = 1 2.6, 3.9 , 1H ) , 3 .67 (d, J = 14 .4 H z, 1H ), 4.0 2 (d, J = 14 .4 H z, 1H ), 6. 70 ( d , J = 3 .3 H z, 1 H) , 7 .28 ( m , 34 6 4H ), 7 .50 (m , 2H ), 9 .17 (s, 1 H ).

LC /M S: co ndi tion 1, ret enti on time = 3.77 mi n LC /M S(ESI ) m /z; 473 [M+ H ] LC /M S(ESI ) m/z ; 38 9 [M - H] H - NMR (C D O D ) δ: 1.4 1-1.7 6 (m, 6 H ) , 1 .96 (m , 2H ), 2 .20 ( tt, J = 12 , 3 .3, 1H ), 3.0 6 (tt, J = 11.7 , 3.6, 1 H ), 3 .65 ( d, J = 14 .4 H z, 1H ), 4.0 2 (d, J = 14 .4 H z, 1H) , 6. 70 ( d, J = 3 .3 H z, 1H ), 7. 02 (t, J = 8. 7 H z, 2 H), 7 .28 ( d, J = 3 .3 Hz , 1H ), 7.5 3 (dd , J = 8 .7, 5 .4 H z, 2H ), 34 7 9.1 7 (s , 1H ) .

LC /M S: co ndi tion 1, ret enti on time = 3.84 mi n LC /M S(ESI ) m /z; 491 [M+ H ] LC /M S(ESI ) m/z ; 48 9 [M - H] TABLE 136 E x D ata H -N MR (D MS O- d ) δ: 1. 56-1. 85 (m, 4H ) , 1.9 2 ( dd, J = 12.7, 2.5 H z, 2H) , 2.03 ( dd, J = 13.1, 3. 3 H z, 2H ), 2.28 (t t, J = 11. 4, 3. 3 H z, 1H ), 3.16 ( tt , J = 11. 9, 3. 7 H z, 1H ), 6. 69 (br s, 1H ) , 6. 82-6. 85 (m , 1H ), 7. 24 ( br s, 1H ), 7. 49 ( t, J = 2. 9 Hz, 1H ) , 9.51 (s, 1H ) , 12.52 ( br s, 1H) .

LC /M S : condi ti on 1, r etent ion t im e = 1. 22 m in LC /M S (E SI ) m /z; 285 [ M+H ] LC /M S (E SI ) m / z; 283 [ M- H] LC /M S : condi ti on 1, r etent ion t im e = 3. 42 m in 349 LC /M S (E SI ) m /z; 379 [ M+H ] LC /M S (E SI ) m / z; 377 [ M- H] H -N MR ( D MS O- d ) δ : 1.67- 1.87 (m , 4H) , 1.91- 2.10 (m , 4H ), 2. 35-2. 43 ( m, 1H ), 3. 14-3. 25 ( m, 1H ), 4. 37 (d, J = 5.7 Hz, 2H) , 6. 84-6. 87 ( m, 1H ), 7. 44 ( d, J = 7. 8 H z, 2 H) , 7.49 (t , J = 2.9 H z, 1H ), 7. 80 ( d, J = 7.8 H z, 2H) , 8.45 (t , J = 5.7 Hz, 1H) , 9.51 (s, 1H) , 12. 52 ( br s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 3. 34 m in LC /M S (E SI ) m /z; 400 [ M+H ] LC /M S (E SI ) m / z; 398 [ M- H] H -N MR ( DM S O- d ) δ: 1 .65- 1.83 (m , 4H ) , 1.88- 2.11 (m, 5H ) , 3. 14-3. 26 ( m, 1H ), 6. 19 (d, J = 7. 8 H z, 1H ), 6. 84-6 .87 ( m, 1H ) , 7. 46-7. 51 (m , 6H ), 9.14 (d, J = 7.8 H z, 1H ), 9. 51 ( s, 1H) , 12.52 (br 351 s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 3. 34 m in LC /M S (E SI ) m /z; 400 [ M+H ] LC /M S (E SI ) m / z; 398 [ M- H] H -N MR ( DM S O- d ) δ: 1 .60- 1.88 (m , 6H ) , 1.98- 2.06 (m, 2H ) , 2. 19-2. 32 (m, 1H) , 2. 69-2. 76 ( m, 2 H) , 3.12- 3.22 (m , 1H ) , 3.25- 3.33 ( m, 2H ), 6. 83-6. 86 ( m, 1H ), 7.24 (d, J = 8. 3 Hz, 2H ), 7 .35 (d, J = 8. 9 H z, 2H ) , 7.50 ( t, J = 2. 6 H z, 1H ), 7. 85 (t , J = 5. 6 H z, 1H) , 9.52 ( s, 1H) , 12. 53 ( br s , 1H) .

LC /M S : condi ti on 1, r etent ion t im e = 3. 84 m in LC /M S (E SI ) m /z; 423 [ M+H ] LC /M S (E SI ) m / z; 421 [ M- H] H -N MR ( DM S O- d ) δ: 1 .55- 1.89 (m , 6H ) , 1.97- 2.05 (m, 2H ) , 2. 26-2. 39 (m, 1H) , 3. 11-3. 22 ( m, 1 H) , 3.26- 3.34 (m , 2H ) , 4.58- 4.66 ( m, 1H ), 5.4 5 (d, J = 4. 5 H z, 1H) , 6.84 (d, J = 3. 3 H z, 1H ), 7. 21-7. 28 (m , 1H ) , 7. 33 (d, J = 4.1 H z, 4H) , 7. 49 ( d, J = 3. 3 Hz, 1H ), 7. 81 ( t, J = 5. 3 H z, 1H ), 9. 51 ( s, 1H ), 12. 52 (br s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 3. 19 m in LC /M S (E SI ) m /z; 405 [ M+H ] LC /M S (E SI ) m / z; 403 [ M- H] TABLE 137 E x D ata H - N MR ( DM S O-d ) δ: 1.65 -1.82 (m , 4 H), 1. 87- 1. 95 (m , 2H ), 2.0 0-2.0 9 (m , 2H ) , 2.36 -2.43 (m, 1H ), 3 .13- 3 .24 (m , 1 H ), 3.8 5-3.9 8 (m, 2H ), 6 .84- 6 .87 (m, 1H ) , 7. 49 (t , J = 2.9 H z, 1H ) , 8 .47 ( t, J = 6. 5 4 H z, 1 H ), 9.51 (s, 1H ), 12 .52 (b r s, 1H ).

LC /M S : co ndi tion 1, ret enti on time = 3.27 mi n LC /M S (E S I ) m /z; 367 [M+ H ] LC /M S (E S I ) m/z ; 36 5 [M - H ] H - N MR ( DM S O-d ) δ: 1.64 -1.82 (m , 4 H), 1. 87- 1. 96 (m , 2H ), 2.0 1-2.0 9 (m, 2 H ) , 2.26 -2.3 9 ( m, 1 H), 3 .14 - 3.25 (m , 1H ) , 4 .15 ( d , J = 5.9 H z, 2 H ), 6.8 5-6. 88 (m , 1 H), 7.5 0 (t, J = 2 .6 H z, 1H ), 8.55 (t, J 5 = 5.3 Hz , 1H ), 9 .52 (s, 1 H ) , 12. 53 ( b r s, 1 H ) .

LC /M S : co ndi tion 1, ret enti on time = 2.65 mi n LC /M S (E S I ) m /z; 324 [M+ H ] LC /M S (E S I ) m/z ; 32 2 [M - H ] H - N MR ( D MS O -d ) δ: 1 .64-1 .82 (m, 4 H) , 1 .87 -1 .95 ( m, 2 H ), 2.0 0-2.0 8 (m , 2H ), 2.2 6- 2.3 7 (m , 1H ) , 2 .66 ( t , J = 6 .6 H z, 2H ) , 3.1 3-3.2 4 (m , 1H ), 3.2 6- 3.3 2 (m , 2H ) , 6 .84-6 .87 (m , 1H ), 7 .50 (t , J = 3.3 Hz , 1H ), 8 .19 (t, J = 5.6 H z , 1H ) , 9 .52 ( s, 1 H ), 12.5 3 (b r s, 6 1H ).

LC /M S : co ndi tion 1, ret enti on time = 2.65 mi n LC /M S (E S I ) m /z; 338 [M+ H ] LC /M S (E S I ) m/z ; 33 6 [M - H ] LC /M S : co ndi tion 1, ret enti on time = 2.90 mi n 7 LC /M S (E S I ) m /z; 364 [M+ H ] LC /M S (E S I ) m/z ; 36 2 [M - H ] LC /M S : co ndi tion 1, ret enti on time = 2.47 mi n 8 LC /M S (E S I ) m /z; 355 [M+ H ] LC /M S (E S I ) m/z ; 35 3 [M - H ] H - N MR ( D MS O -d ) δ: 0 .39 (d d, J = 4.3 , 2.6 H z, 2 H), 0.61 (dd , J = 6.9 , 2.3 H z, 2 H), 1.6 1-1.7 8 (m, 4H ), 1.8 0- 1.8 9 (m , 2H ) , 1. 98-2.0 7 (m, 2H ), 2.1 6- 2. 28 (m , 1H ) , 2 .60- 2 .68 ( m , 1H ), 3.11 -3.22 (m, 1 H ), 6.8 4 (dd , J = 3 .3, 2 .0 H z , 1H ), 7 .50 ( t, J = 3 .0 H z, 1H ) , 7. 83 ( d , J = 9 4.3 H z, 1 H), 9.52 (s, 1 H ), 12 .53 (b r s, 1 H ).

LC /M S : co ndi tion 1, ret enti on time = 2.92 mi n LC /M S (E S I ) m /z; 325 [M+ H ] LC /M S (E S I ) m/z ; 32 3 [M - H ] H - N MR ( D MS O -d ) δ: 1 .62-1 .80 (m, 4 H) , 1 .83 -1 .92 ( m, 2 H ), 1.9 9-2.0 7 (m , 2H ), 2.2 6- 2.3 7 (m , 1H ) , 3 .10-3 .19 (m , 1H ), 3 .32-3 .44 (m, 4H ), 4.6 5 (t, J = 5.6 H z, 1 H ), 6.8 3-6.8 7 (m , 1H ), 7. 48- 7 .5 2 (m , 36 0 1H ), 7 .76 (t , J = 5. 9 H z, 1H ), 9.5 2 ( s , 1H ) , 1 2.5 3 (br s , 1H ).

LC /M S : co ndi tion 1, ret enti on time = 2.34 mi n LC /M S (E S I ) m /z; 329 [M+ H ] LC /M S (E S I ) m/z ; 32 7 [M - H ] TABLE 138 E x D ata H -N MR ( DM S O- d ) δ: 1 .55- 1.70 (m , 2H ) , 1.76- 1.87 (m, 4H ) , 1. 97-2. 06 (m , 2H ), 2. 32-2. 46 (m , 1H ), 3. 12-3. 23 (m , 1H ), 3.58 (dd, J = 10. 2, 3. 6 H z, 1H ), 3.89 -3.9 6 (m , 1H ) , 3. 99-4. 07 (m , 1H ), 4. 41-4. 49 (m , 1H ), 5.68- 5.73 (m , 1H) , 6. 88 (dd, J = 3. 3, 2. 0 H z, 2H ), 7. 49 ( t, J = 3. 0 H z, 1H ), 9. 51 ( s, 1H ), 12. 52 (br s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 1. 79 m in LC /M S (E SI ) m /z; 341 [ M-H ] LC /M S (E SI ) m / z; 339 [ M- H] H -N MR ( DM S O- d ) δ: 1 .59- 1.86 (m , 6H ) , 1.98- 2.06 (m, 3H ) , 2. 19-2. 30 (m , 2H ), 2.83 ( t, J = 7. 3 H z, 2H ), 3.15 -3.25 ( m, 1H) , 6. 83-6. 86 (m , 1H ), 7. 43 (d, J = 7.9 H z, 2H ) , 7 .50 (t , J = 3. 0 H z, 1H ), 7.78 ( d, J = 7. 6 Hz, 2H) , 7. 87 (t , J = 5. 6 Hz, 1H ), 9. 52 (s, 1H) , 12. 53 ( br s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 3. 40 m in LC /M S (E SI ) m /z; 414 [ M+H ] LC /M S (E SI ) m / z; 412 [ M- H] H -N MR ( D MS O- d ) δ : 1.56- 1.70 (m , 2H) , 1.73- 1.91 (m , 4H ), 1. 97-2. 06 ( m, 2H ), 2. 33-2. 44 ( m, 1H ), 3. 13-3. 25 (m, 1H ) , 3.74-3. 86 ( m, 1H ), 3. 97-4. 05 ( m, 1H ) , 4.11- 4.20 (m , 1H) , 4.41- 4.56 (m , 2H ), 6. 89 ( dd, J = 3. 3, 2. 0 H z, 1H ), 7. 49 ( t, J = 2. 6 H z, 1H ), 9. 51 ( s, 1H ), 12. 52 (br s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 2. 88 m in LC /M S (E SI ) m /z; 350 [ M+H ] LC /M S (E SI ) m / z; 348 [ M- H] H -N MR ( CD Cl ) δ: 1.30- 1.40 (m , 2H ), 1. 81-2. 02 ( m, 2H) , 2.05- 2.25 ( m, 5H ) , 3.10 ( d, J = 6.0 H z, 2H ), 3.12- 3.21 ( m, 1H ) , 6.76 (dd , J = 3. 6, 2. 1 H z, 1 H) , 7. 29 (t, J = 3.0 H z, 1H) , 7. 55-7. 73 ( m, 3H ), 364 7. 91-7. 99 ( m, 2H ), 9. 00 ( br s, 1H ), 9. 21 ( s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 2. 00 m in LC /M S (E SI ) m /z; 396 [ M+H ] LC /M S (E SI ) m / z; 394 [ M- H] H -N MR ( CD Cl ) δ: 1.31- 1.56 (m , 2H ), 1. 86-2. 02 ( m, 2H) , 2.06- 2.24 ( m, 5H ) , 3.09 ( d, J = 6.0 H z, 2H ), 3.11- 3.22 ( m, 1H ) , 6.76 (dd , J = 6. 0, 2. 4 Hz, 1H ), 7.2 2-7. 31 (m , 3H ), 7 .93- 8.00 ( m, 2H ) , 9. 13 (br s , 365 1H ), 9. 21 ( s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 2. 06 m in LC /M S (E SI ) m /z; 414 [ M+H ] LC /M S (E SI ) m / z; 412 [ M- H] H -N MR ( D MS O- d ) δ : 0.96- 1.07 (m , 4H) , 1.31- 1.51 (m , 2H ), 1. 70-1. 91 ( m, 2H ), 1. 95-2. 18 ( m, 4H ), 2. 69-2. 84 (m, 1H ) , 3.15 (d, J = 5. 7 H z, 2H ), 3. 65 ( s, 2H ), 6. 81 ( dd, J = 3. 3, 1. 8 H z, 1H ), 7. 49 ( t, 366 J = 2.7 H z, 1 H) , 9.51 (s , 1H) , 12.52 (br s , 1H) .

LC /M S : condi ti on 3, r etent ion t im e = 1. 51 m in LC /M S (E SI ) m /z; 360 [ M+H ] LC /M S (E SI ) m / z; 358 [ M- H] TABLE 139 E x D ata H -N MR ( CD Cl ) δ: 1.20- 1.38 (m , 2H ), 1. 58-1. 67 ( m, 1H) , 1.87- 2.05 ( m, 2H ), 2. 06-2. 21 ( m, 4H ), 3. 09-3. 19 ( m, 1H ), 3. 22 ( d, J = 6.0 Hz , 2H ), 6. 78 ( dd, J = 3. 0, 1.8 Hz, 1H ), 7. 29 ( t, J = 3. 0 H z, 1H ), 9.11 ( br s, 1H) , 9.22 (s , 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 2. 42 m in LC /M S (E SI ) m /z; 382 [ M+H ] H -N MR ( CD Cl ) δ: 1.51- 1.56 (m , 2H ), 1. 92-2. 12 ( m, 2H) , 2.13- 2.32 ( m, 4H ), 2. 33-2. 51 ( m, 1H ), 3. 11-3. 20 ( m, 1H ), 3. 21 ( d, J = 6.6 Hz , 2H ), 6. 77 ( dd, J = 6. 0, 2.1 Hz, 1H ), 7. 30 ( t, J = 6. 0 H z, 1H ), 9.11 368 ( br s, 1H) , 9.22 (s , 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 2. 16 m in LC /M S (E SI ) m /z; 388 [ M+H ] LC /M S (E SI ) m / z; 386 [ M- H] H -N MR ( CD Cl ) δ: 1.20- 1.38 (m , 2H ), 1. 70-1. 85 ( m, 1H) , 1.85- 2.08 ( m, 4H ), 2. 11-2. 22 ( m, 2H ), 3. 10-3. 22 ( m, 1H ), 3. 26 ( d, J = 6.6 Hz , 2H ), 6. 78 ( dd, J = 3. 3, 2.4 Hz, 1H ), 7. 29 ( t, J = 2. 7 H z, 1H ), 9.14 369 ( br s, 1H) , 9.22 (s , 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 2. 09 m in LC /M S (E SI ) m /z; 297 [ M+H ] LC /M S (E SI ) m / z; 295 [ M- H] H -N MR ( D MS O- d ) δ : 1.22- 1.40 (m , 2H) , 1.47 (s, 6H ), 1.64- 1.83 ( m, 3H ), 1. 91-2. 09 ( m, 3H ) , 2.41- 2.57 (m , 1H) , 3.21- 3.36 (m , 1H ), 3. 30 ( br s, 1H ), 4. 26 ( d, J = 6. 9 H z, 1H ), 5. 07 (s, 1H ), 6. 85-6. 90 ( m, 1H ), 7. 42-7. 52 ( m, 1H ) , 7.89 (s, 1H ), 9. 52 ( s, 1H ), 12. 53 ( s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 1. 53 m in LC /M S (E SI ) m /z; 381 [ M+H ] LC /M S (E SI ) m / z; 379 [ M- H] H -N MR ( D MS O- d ) δ : 1.06- 1.24 (m , 2H) , 1.29- 1.45 (m , 1H ), 1. 66-1. 84 ( m, 2H ), 1. 87-2. 07 ( m, 4H ), 2. 40-2. 54 (m, 2H ) , 3.05-3. 20 ( m, 1H ), 3. 30 ( br s, 1H ), 6. 79 ( d, J = 3. 3 Hz, 1H ) , 7.48 (d, J = 3. 3 H z, 1H ), 9. 50 ( s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 0. 99 m in LC /M S (E SI ) m /z; 271 [ M+H ] H -N MR ( D MS O- d ) δ : 1.12- 1.31 (m , 2H) , 1.52- 1.63 (m , 1H ), 1. 64-1. 82 ( m, 2H ), 1. 82-2. 07 ( m, 4H ), 3. 04 (t, J = 6. 6 H z, 2H ), 3. 08-3. 20 ( m, 1H ), 3. 65 ( s, 2H ), 6. 80 ( dd, J = 3. 0, 1.8 H z, 1H ), 7. 48 ( t, J = 3.0 H z, 1H ), 8. 19-8. 28 (m , 1H ), 9. 51 ( s, 1H ), 12. 51 ( br s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 1. 51 m in LC /M S (E SI ) m /z; 338 [ M+H ] LC /M S (E SI ) m / z; 336 [ M- H] H -N MR ( D MS O- d ) δ : 1.12- 1.32 (m , 2H) , 1.46- 1.64 (m , 1H ), 1. 65-1. 82 ( m, 2H ), 1. 82-2. 07 ( m, 4H ), 3. 05 (t, J = 6. 0 H z, 2H ), 3. 07-3. 20 ( m, 1H ), 3. 23 ( d, J = 11. 6 H z, 1H) , 3.27- 3.35 (m , 1H) , 6. 79 ( dd, J = 3. 0, 1. 8 H z, 1H ), 7. 48 ( t, J = 3. 0 H z, 1H ), 8. 18-8. 31 ( m, 1H ), 9. 51 ( s, 1H ), 12. 51 ( br s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 1. 75 m in LC /M S (E SI ) m /z; 381 [ M+H ] LC /M S (E SI ) m / z; 379 [ M- H] TABLE 140 E x D ata H -N MR ( D MS O- d ) δ : 1.85- 2.02 (m , 4H) , 2.13- 2.30 (m , 2H ), 2.36 ( s, 3H) , 2.8 6-2. 99 ( m, 2H ), 3. 10-3. 24 ( m, 1H ) , 3.67 (s, 2H ), 5. 09 ( q, J = 9.0 H z, 2 H) , 6.81 (d, J = 3. 3 H z, 1H ), 7. 49 ( d, J = 3.3 Hz, 1 H) , 374 9. 52 ( s, 1H ), 12. 54 ( br s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 1. 50 m in LC /M S (E SI ) m /z; 381 [ M+H ] LC /M S (E SI ) m / z; 379 [ M- H] H -N MR ( D MS O- d ) δ : 1.86- 2.04 (m , 4H) , 2.16- 2.32 (m , 2H ), 2.62 ( t, J = 7.5 H z, 2H ), 2. 89 ( t, J = 7.5 H z, 2H ), 3. 01-3. 12 (m , 2H ), 3. 12-3. 24 ( m, 1H ), 6. 76 ( d, J = 3. 3 H z, 1 H) , 7.47 (d, J = 3.3 H z, 1H ), 7. 49 ( d, J = 7.8 H z, 2H) , 7.76 (d, J = 7. 8 H z, 2H ), 9. 52 ( s, 1H ), 12. 53 ( br s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 1. 38 m in LC /M S (E SI ) m /z; 372 [ M+H ] LC /M S (E SI ) m / z; 370 [ M- H] H -N MR ( CD C l ) δ: 2 .19- 2.28 (m, 4 H) , 3.14- 3.23 (m , 2H) , 3.46- 3.53 ( m, 1H ), 4. 06 ( d, J = 12.6 Hz, 2H ) , 6.67 (dd, J = 3.3, 2. 4 Hz, 1H ) , 6. 96 ( d, J = 9. 0 H z, 2 H) , 7.53 (d, J = 9. 0 H z, 2H ), 9. 06 ( br s, 1H ), 376 9. 24 ( s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 2. 07 m in LC /M S (E SI ) m /z; 344 [ M+H ] LC /M S (E SI ) m / z; 342 [ M- H] H -N MR ( D MS O- d ) δ : 1.90- 2.08 (m , 4H) , 2.11- 2.30 (m , 2H ), 2. 70-2. 76 ( m, 1H ), 2. 87-3. 01 ( m, 2H ), 3. 62 (s, 2H ), 7. 56 ( d, J = 8 .3 H z, 2H ), 7. 66 ( s, 1H ), 7. 80 ( d, J = 3. 3 H z, 2H ), 9. 51 (s, 1H ), 12.51 377 ( br s, 1H) .

LC /M S : condi ti on 3, r etent ion t im e = 1. 45 m in LC /M S (E SI ) m /z; 392, 394 [ M+H ] LC /M S (E SI ) m / z; 390, 392 [ M- H] H -N MR ( CD C l ) δ: 1 .56 (m , 2H ) , 1.94- 2.07 (m , 8H) , 2.20 -2.33 (m , 6H ), 3. 01-3. 26 (m, 7H ), 3. 41 (m, 1H ) , 4.26 (d, J = 5.4 H z, 1H ), 4. 34 ( d, J = 5. 4 H z, 1H ), 4.44 (m , 2H) , 6.77 (m , 1H ), 6. 80 (m , 1H ), 7. 22-7. 32 ( m, 10H ), 9. 22 ( s, 2H ), 10. 04 ( br s, 2H ).

LC /M S : condi ti on 1, r etent ion t im e = 0. 99, 1.25 mi n (ci s/t rans mi xt ure) LC /M S (E SI ) m /z; 389 [ M+H ] LC /M S (E SI ) m / z; 387 [ M- H] H -N MR ( CD C l ) δ: 1 .57 (m , 2H ) , 1.94- 2.07 (m , 8H) , 2.19 -2.32 (m , 6H ), 3. 01-3. 22 (m, 7H ), 3. 41 (m, 1H ) , 4.27 (d, J = 5.4 H z, 1H ), 4. 34 ( d, J = 5. 4 H z, 1H ), 4.44 (m , 2H) , 6.76 (m , 1H ), 6. 80 (m , 1H ), 7. 22-7. 30 ( m, 10H ), 9. 22 ( s, 2H ), 10. 28 ( br s, 2H ).

LC /M S : condi ti on 1, r etent ion t im e = 0. 87, 1.03 mi n (ci s/t rans mi xt ure) LC /M S (E SI ) m /z; 389 [ M+H ] LC /M S (E SI ) m / z; 387 [ M- H] TABLE 141 E x D ata H -N MR ( D MS O- d ) δ : 1.58 (m , 6H) , 1.75- 1.84 (m , 12H ), 2. 02 (m , 4H ), 2. 17 ( m, 2H ) , 2.60 (m , 12H) , 2.75 (m , 3H ), 2. 82 (m , 12H ), 3. 17 ( m, 2H ), 3. 51 ( m, 1H ) , 6.82 (m , 1H) , 6.88 (m , 2H) , 7.48 (m , 3H ), 380 9. 50 ( s, 2H ), 9. 52 ( s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 2. 75 m in LC /M S (E SI ) m /z; 363 [ M+H ] LC /M S (E SI ) m / z; 361 [ M- H] H -N MR ( D MS O- d ) δ : 1.76- 1.96 (m , 6H) , 2.10- 2.23 (m , 2H ), 3. 30-3. 40 ( m, 1H ), 3. 49-3. 57 ( m, 1H ), 5. 57 (d, J = 6.9 Hz, 1H) , 6. 61-6. 68 ( m, 2H ), 6. 86-6. 94 ( m, 3H ), 7. 50 (t, J = 2. 6 H z, 1H ), 9. 53 ( s, 1H) , 12. 53 ( br s , 1H) .

LC /M S : condi ti on 1, r etent ion t im e = 3. 22 m in LC /M S (E SI ) m /z; 351 [ M+H ] LC /M S (E SI ) m / z; 349 [ M- H] H -N MR ( D MS O- d ) δ : 1.41 (qd, J = 12. 9, 3.6 Hz, 2H ) , 1.84- 2.19 ( m, 6H ), 3. 20 ( tt , J = 11.9, 3. 6 H z, 1H ), 3.31- 3.39 (m , 1H) , 5.37 (d, J = 8.3 H z, 1 H) , 6.60 -6.6 6 (m , 2H ), 6. 86-6. 95 ( m, 3H ), 7. 50 ( d, J = 3. 3 H z, 1H ), 9. 53 ( s, 1H ), 12. 54 ( br s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 2. 82 m in LC /M S (E SI ) m /z; 351 [ M+H ] LC /M S (E SI ) m / z; 349 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 1. 51 m in 382 + + LC /M S (E SI ) m /z; 392, 399 [ M+H ] LC /M S (E SI ) m / z; 390, 397 [ M- H] H -N MR ( CD C l ) δ: 1 .26- 1.46 (m, 2 H) , 1.87- 2.05 (m , 2H) , 2.08- 2.23 ( m, 4H ), 2. 76-2. 91 ( m, 1H ) , 3.10- 3.24 (m , 1H) , 3.44 (d, J = 12. 5 H z, 1H ), 3. 48 ( d, J = 12.5 Hz, 1H ) , 6.76 (dd, J = 3.3, 1.8 Hz, 1 H) , 7.29 ( t, J = 3.3 H z, 1H ), 9. 08 ( br s, 1H) , 9.2 1 (s , 1H) .

LC /M S : condi ti on 3, r etent ion t im e = 1. 28 m in LC /M S (E SI ) m /z; 399 [ M+H ] LC /M S (E SI ) m / z; 397 [ M- H] H -N MR ( D MS O- d ) δ : 1.60- 1.75 (m , 4H) , 1.77- 1.88 (m , 2H ), 2. 12-2. 25 ( m, 1H ), 2. 25-2. 37 ( m, 1H ), 2. 85-2. 92 (m, 1H ) , 3.20-3. 40 ( m, 3H ), 6. 98 ( dd, J = 3. 3, 2. 0 H z, 1H ), 7. 45 (t, J = 2. 6 H z, 1H ), 9. 52 ( s, 1H ), 12. 51 ( br s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 2. 90 m in LC /M S (E SI ) m /z; 389 [ M+H ] LC /M S (E SI ) m / z; 387 [ M- H] H -N MR ( D MS O- d ) δ : 1.23- 1.39 (m , 2H) , 1.70- 1.86 (m , 2H ), 1. 96-2. 09 ( m, 4H ), 2. 17-2. 28 ( m, 1H ), 2. 54-2. 65 (m, 1H ) , 3.14 (tt , J = 12. 2, 3.0 H z, 1 H) , 3.33 -3.4 5 (m , 2H ), 6. 82 ( d, J = 2. 6 H z, 1 H) , 7. 49 ( d, J = 2. 6 H z, 1 H) , 9.52 (s, 1H ) , 12.53 (br s, 1H ) .

LC /M S : condi ti on 1, r etent ion t im e = 1. 84 m in LC /M S (E SI ) m /z; 389 [ M+H ] LC /M S (E SI ) m / z; 387 [ M- H] TABLE 142 Ex Data H - NMR ( DMSO -d ) δ: 1 .58-1 .86 (m, 6 H) , 2 .09 -2 .30 ( m, 2 H ), 2.4 1-2.5 4 (m , 1H ), 2.6 9- 2.8 1 (m , 1H ) , 3 .25 ( s , 2H ), 3 .88 - 4.05 ( m, 2H ), 6 .94-6 .98 (m , 1H ), 7 .44 (t, J = 3 .0 H z , 1H ), 8 .32-8 .45 (m , 1 H), 38 4 9.5 1 (s , 1H ) , 12 .49 ( s, 1 H) .

LC /M S: co ndi tion 3, ret enti on time = 1.35 mi n LC /M S(ESI ) m /z; 396 [M+ H ] LC /M S(ESI ) m/z ; 39 4 [M - H] H - NMR ( DMSO -d ) δ: 1 .25-1 .41 (m, 2 H) , 1 .67 -1 .84 ( m, 2 H ), 1.9 4-2.0 5 (m , 4H ), 2.4 4- 2.5 7 (m , 1H ) , 3 .06-3 .20 (m , 1H ), 3 .26 (s , 2H ), 3 .87-4 .02 (m , 2H ), 6 .78 (dd, J = 3.0 , 1.5 H z, 1 H), 7 .48 (t, J = 38 4 3.0 H z, 1 H), 8.41 (br s , 1H ), 9 .50 (s , 1H ), 1 2.5 1 (s, 1H ) .

LC /M S: co ndi tion 3, ret enti on time = 1.22 mi n LC /M S(ESI ) m /z; 396 [M+ H ] LC /M S(ESI ) m/z ; 39 4 [M - H] H - NMR ( CD O D ) δ : 1.3 5 ( m, 2H ), 1.8 4 (m , 2H) , 2.0 7 ( m, 4 H ), 2.5 8 (tt, J = 1 1.4 , 3 .3 H z, 1H ), 3.16 (t t, J = 1 2.3 , 3 .3 Hz, 1H ) , 3 .36 ( d , J = 1 3.5 H z, 1H ), 3. 46 (d, J = 12.9 H z , 1 H) , 6 .77 ( d, J = 3.3 H z , 1H ), 7.3 8 (d , J = 3.3 H z, 1 H ), 7.5 0 (d d, J = 7. 5, 4 .2 H z , 1H ), 8.10 (d, J = 38 5 8.1 H z , 1 H ), 8 .55 (dd , J = 5.1 , 1 .2 H z, 1H) , 8.8 1 (d, J = 1 .2 H z, 1H ), 9 .27 (s , 1H ) .

LC /M S: co ndi tion 1, ret enti on time = 0.39 mi n LC /M S(ESI ) m /z; 446 [M+ H ] LC /M S(ESI ) m/z ; 44 4 [M - H] H - NMR ( CD O D ) δ : 1.4 3 ( m, 2H ), 1.8 4 (m , 2H) , 2.0 9 ( m, 4 H ), 2.4 9 (s, 3H ), 2.6 9 (tt, J = 11. 1, 3.6 H z, 1 H), 3 .17 (tt, J = 12 .3, 3.3 H z , 1H ), 3.38 (d, J = 13 .2 H z, 1 H ), 3. 45 (d, J = 12. 9 Hz , 1 H) , 6.7 7 (d , J 38 6 = 3.3 H z, 1H) , 7.3 1 ( d, J = 8 .7 H z, 2 H) , 7 .38 (d , J = 3.3 H z , 1H ), b 7.5 7 (d, J = 8.7 H z, 2H ), 9.2 7 (s , 1H ).

LC /M S: co ndi tion 1, ret enti on time = 2.92 mi n LC /M S(ESI ) m /z; 491 [M+ H ] LC /M S(ESI ) m/z ; 48 9 [M - H] H - NMR ( CD O D ) δ : 1.4 0 ( m, 2H ), 1.8 5 (m , 2H) , 2.1 0 ( m, 4 H ), 2.6 5 (tt, J = 1 1.4 , 3 .6 H z, 1H ), 3.17 (t t, J = 1 2.3 , 3 .6 Hz, 1H ) , 3 .35 ( d , J = 13 .5 Hz , 1 H ), 3.4 2 (d, J = 13.2 H z, 1H ), 3.9 3 (s , 3 H), 6.7 7 (d, J = 38 7 3.3 H z, 1H ), 6 .84 (d, J = 8.7 Hz , 1 H ) , 7. 38 ( d, J = 3 .3 H z , 1 H ), 7.8 9 b (s, 1H ) , 8.3 8 ( d, J = 2 .4 H z, 1 H ), 9.2 7 ( s , 1H) .

LC /M S: co ndi tion 1, ret enti on time = 2.49 mi n LC /M S(ESI ) m /z; 476 [M+ H ] LC /M S(ESI ) m/z ; 47 4 [M - H] H - NMR ( CD O D ) δ : 1.4 2 ( m, 2H ), 1.8 2 (m , 2H) , 2.1 0 ( m, 4 H ), 2.6 8 (tt, J = 11.4 , 3.6 , 1 H ), 3.1 7 (tt , J = 12 .6, 3.3 Hz, 1H ), 3. 37 (d , J = 13 .2 H z, 1H) , 3 .43 ( d, 13 .2 H z, 1H ), 3.81 ( s , 3H) , 6.7 7 ( d, J = 3 .3 38 8 H z, 1H ), 6.97 (d , J = 9.0 Hz, 2H ) , 7.3 8 ( d , J = 3.3 H z, 1 H), 7.5 6 (d, b J = 8 .4 H z, 2H ), 9.2 7 (s , 1H ).

LC /M S: co ndi tion 1, ret enti on time = 2.75 mi n LC /M S(ESI ) m /z; 475 [M+ H ] LC /M S(ESI ) m/z ; 47 3 [M - H] TABLE 143 Ex Data H - NMR ( CD C l ) δ : 0.8 7 ( m , 2H ), 1 .34 ( m , 2 H), 1.73 (m, 2 H), 1.96 (m, 2H ), 2.1 5 (m , 4H ), 2 .68- 2 .79 (m , 3H ) , 3 .18 ( m, 1 H), 6.77 ( d, J = 3.3 H z, 1 H), 6.90 - 7.04 (m, 4H ) , 7.2 8 ( d, J = 3.3 Hz, 1 H ), 9.1 6 ( br s , 38 9 1H ), 9 .21 (s , 1H ) .

LC /M S: co ndi tion 1, ret enti on time = 2.75 mi n LC /M S(ESI ) m /z; 405 [M+ H ] LC /M S(ESI ) m/z ; 40 3 [M - H] H - NMR ( CD C l ) δ : 1.3 3 ( m , 2H ), 1 .92 ( m , 2 H), 2.17 (m, 4 H), 2.68 (tt, J = 11. 1, 3. 3, 1 H ), 3.08 (d, J = 12. 6H z, 1 H ), 3.1 6 ( tt, J = 12 .3, 3.9 H z, 1 H), 3.58 (d, J = 12 H z , 1H ), 3 .89 (s, 3 H ), 3.60 ( s, 3H ), 39 0 6.7 3 (d, J = 3.0 H z, 1H ), 6.8 8 (d , J = 8. 7 H z, 1H ), 7.0 7 (d, J = 8 .4 b H z, 1 H ), 7.21 (m, 1H) , 7.2 9 (m , 1H) , 9 .21 ( s , 1H ), 9 .41 (br s , 1H ).

LC /M S: co ndi tion 1, ret enti on time = 2.67 mi n LC /M S(ESI ) m /z; 505 [M+ H ] LC /M S(ESI ) m/z ; 50 3 [M - H] H - NMR ( CD O D ) δ : 1.4 0 ( m, 2H ), 1.9 0 (m , 2H) , 2.1 4 ( m, 4 H ), 2.7 1 (m, 1H) , 2.9 4 (s , 4H) , 3.29 (m , 1 H ), 6 .82 ( d, J = 3 .3 Hz, 1H ), 7.4 0(d, J = 3 .3 H z, 1H ), 7.4 6 ( d , J = 8.1 H z, 2H) , 7.6 7 ( d, J = 8 .4 39 1 H z, 2 H ) 9.30 ( s, 1 H) .

LC /M S: co ndi tion 1, ret enti on time = 1.62 mi n LC /M S(ESI ) m /z; 386 [M+ H ] LC /M S(ESI ) m/z ; 38 4 [M - H] H - NMR ( CD C l ) δ : 0.4 0 ( m , 2H ), 0 .50 ( m , 2 H), 1.37 (m, 2 H), 1.98 (m, 2H ), 2.1 4- 2. 26( m , 5H ), 2. 82 ( m , 1H ), 3. 18 (tt , J = 1 2.3 , 3.3 H z, 1H ), 3 .71, 6.78 ( d, J = 3.3 Hz , 1H ) , 7 .30 ( d, J = 3.3 Hz , 1H ), 9.23 39 2 (s, 1H ) .

LC /M S: co ndi tion 1, ret enti on time = 3.55 mi n LC /M S(ESI ) m /z; 424 [M+ H ] LC /M S(ESI ) m/z ; 42 2 [M - H] H - NMR ( CD C l ) δ : 1.4 2 ( m , 2H ), 1 .95-2. 20 (m , 6H ), 2 .92 (m , 1H ), 3.2 1 (tt, J = 12 .6, 3 .6 H z , 1H ), 3 .71 (d , J = 7 .8 H z , 2H ), 6 .78 (d, J = 39 3 3.3 H z, 1 H), 7.31 (d, J = 3.3 Hz , 1H) , 9.23 (s, 1H ). b LC /M S: co ndi tion 1, ret enti on time = 0.35 mi n LC /M S(ESI ) m /z; 296 [M+ H ] LC /M S(ESI ) m/z ; 29 4 [M - H] H - NMR ( CD C l ) δ : 1.3 7 ( m , 2H ), 1 .96 ( m , 2 H), 2.16 (m, 4 H), 2.56 (t, J = 6.6 Hz , 2 H) , 2.71 ( tt, J = 11.7 , 3. 6 Hz, 1 H ), 3.0 4 ( t, J = 6.6 H z, 2 H ), 3.18 (tt, J = 11 .7, 3 .9 H z, 1H ), 6 .77 (d d, J = 3.3, 2.1 H z, 39 4 1H ), 7 .30 (t , J = 2. 7 Hz, 1H ), 9.2 2 ( s , 1H) , 9 .36 (br s, 1H) .

LC /M S: co ndi tion 1, ret enti on time = 0.35 mi n LC /M S(ESI ) m /z; 310 [M+ H ] LC /M S(ESI ) m/z ; 30 8 [M - H] TABLE 144 E x D ata H -N MR ( CD C l ) δ: 1 .38 (m , 2H ) , 1.96 (m , 2H ), 2. 17 (m , 4H ), 2. 78 ( tt , J = 11. 1, 3. 3 H z, 1H ), 3. 18 ( tt , J = 12.4, 3. 3 H z, 1H ), 3. 29 (q, J = 9. 6 H z, 2H ), 6. 76 ( dd, J = 3. 3, 2. 1 H z, 1H ), 7 .30 (t , J = 2. 7 Hz, 1H ), 9. 22 ( s, 1H ), 9. 43 ( br s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 0. 37 m in LC /M S (E SI ) m /z; 339 [ M+H ] LC /M S (E SI ) m / z; 337 [ M- H] H -N MR ( CD C l ) δ: 0 .16 (m , 2H ) , 0.51 (m , 2H ), 1. 01 (m , 1H ), 1. 42 ( m, 2H ), 1. 98 ( m, 2H ) , 2.17 (m , 4H) , 2.60 (d, J = 6.9 H z, 2H ), 2. 72 ( tt , J = 11. 1, 3. 9 H z, 1H ), 3. 19 ( tt , J = 12.3, 3. 3 H z, 1H ), 6. 77 (d, J = 3. 3 H z, 1H ), 7. 31 ( d, J = 3. 3 Hz, 1H ) , 9.23 (s , 1H) .

LC /M S : condi ti on 1, r etent ion t im e = 0. 37 m in LC /M S (E SI ) m /z; 311 [ M+H ] LC /M S (E SI ) m / z; 309 [ M- H] H -N MR ( CD O D) δ: 1. 51 ( m, 2H ), 1. 95 ( m, 2H ), 2. 18 ( m, 4H ) , 2 .39 ( s, 6H ) , 2. 42 (m , 1H ), 3.15 ( tt , J = 11.7, 3. 9 H z, 1H ) , 6. 79 ( d, J = 3. 3 H z, 1H ), 7. 29 ( d, J = 3. 3 H z, 1H ) , 9.22 (s, 1H ) . b LC /M S : condi ti on 1, r etent ion t im e = 0. 35 m in LC /M S (E SI ) m /z; 285 [ M+H ] LC /M S (E SI ) m / z; 283 [ M- H] H -N MR ( CD C l ) δ: 1 .33 (m , 2H ) , 1.93 (m , 2H ), 2. 15 (m , 4H ), 2. 51 ( s, 3H) , 2.5 6 (m , 1H ), 3. 18 ( tt , J = 12.3, 3. 6 Hz, 1H ), 6 .78 (d, J = 398 3. 6 Hz, 1H) , 7.28 (d, J = 3. 3 H z, 1H ), 9. 21 (s, 1H ). b LC /M S : condi ti on 1, r etent ion t im e = 0. 35 m in LC /M S (E SI ) m /z; 271 [ M+H ] LC /M S (E SI ) m / z; 269 [ M- H] H -N MR ( CD C l ) δ: 1 .37 (m , 2H ) , 1.97 (m , 2H ), 2. 17 (m , 4H ), 2. 72 ( tt , J = 11. 4, 3. 6 H z, 1H ), 3. 08 ( td, J = 15. 3, 4.5 H z, 2H) , 3.1 8 (t t , J = 12. 3, 3.3 H z, 1 H) , 5.88 (m , 1H ), 6. 77 ( m, 1H ), 7. 31 (m, 1H ) , 9.23 ( s, 1H) , 9.5 9 (b r s , 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 0. 81 m in LC /M S (E SI ) m /z; 321 [ M+H ] LC /M S (E SI ) m / z; 319 [ M- H] H -N MR ( CD C l ) δ: 1 .45 (m , 2H ) , 1.96 (m , 2H ), 2. 16 (m , 4H ), 2. 97 ( m, 1H ), 3. 18 ( tt , J = 12.0, 3. 6 H z, 1H ), 3.79 (m , 1H) , 6.7 7 (m , 1H ), 400 7. 31 ( m, 1H ), 9. 17 ( br s, 1H ), 9. 23 ( s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 4. 04 m in LC /M S (E SI ) m /z; 407 [ M+H ] LC /M S (E SI ) m / z; 405 [ M- H] H -N MR (C D OD ) δ: 1. 71-2. 18 (m , 9H ), 3. 33-3. 45 (m , 1H ), 3.67 (d, J = 6 .6 H z, 2H ), 6. 80 ( d, J = 3. 3 H z, 1H ), 7. 39 (d, J = 3.3 H z, 1H ) , 9. 30 ( s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 1. 53 m in LC /M S (E SI ) m /z; 272 [ M+H ] LC /M S (E SI ) m / z; 270 [ M- H] TABLE 145 E x D ata H -N MR ( CD C l ) δ: 1 .76- 1.91 (m, 2 H) , 1.95- 2.06 (m , 4H) , 2.32- 2.44 ( m, 2H ), 2. 54-2. 64 ( m, 1H ) , 3.26- 3.38 (m , 1H) , 6.78 (dd, J = 3.3, 1. 8 H z, 1H ), 7. 29 ( t, J = 3. 0 H z, 1H ), 9. 19 ( br s, 1H ), 9. 22 ( s, 1H ), 402 9. 84 ( s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 1. 71 m in LC /M S (E SI ) m /z; 270 [ M+H ] LC /M S (E SI ) m / z; 268 [ M- H] H -N MR ( D MS O- d ) δ : 1.56- 1.99 (m , 10H) , 2.39 (d, J = 6. 3 H z, 2H ), 2. 65 ( dd, J = 7. 4, 6. 0 H z, 2H ), 3. 50 ( dd, J = 7. 4, 6. 0 H z, 2H ), 4. 14 ( dd, J = 9. 8, 3.3 H z, 2H ), 6.76 (d, J = 3. 3 H z, 1H ), 7. 47 ( d, J = 3. 3 H z, 1H ), 9. 50 ( s, 1H ), 12. 50 ( br s, 1H) .

LC /M S : condi ti on 1, r etent ion t im e = 0. 94 m in LC /M S (E SI ) m /z; 327 [ M+H ] H -N MR ( D MS O- d ) δ : 1.47- 1.62 (m , 1H) , 1.63- 1.85 (m , 4H ), 1. 89-2. 07 ( m, 3H ), 2. 24-2. 59 ( m, 6H ), 2. 65-2. 75 (m, 1H ) , 3.22-3. 44 ( m, 1H ), 4. 08-4. 29 ( m, 1H ) , 4.62 (d, J = 4.5 H z, 1H) , 2.86- 2.98 (m , 404 1H ), 3. 29-3. 39 (m, 1H ), 6. 77 (d, J = 3.3 H z, 1H) , 7.48 (d, J = 3. 3 H z, 1H ), 9. 51 ( s, 1H ), 12. 51 ( br s, 1H) .

LC /M S : condi ti on 3, r etent ion t im e = 0. 95 m in LC /M S (E SI ) m /z; 341 [ M+H ] H -N MR ( CD C l ) δ: 1 .59- 1.96 (m, 7 H) , 2.06- 2.31 (m , 5H) , 2.42- 2.61 ( m, 3H ), 2. 75 ( d, J = 9.8 Hz, 1H ) , 2.86- 2.98 (m , 1H ), 3. 29-3.39 (m , 1H ), 4. 26-4. 37 (m, 1H ), 6. 77 (d, J = 3.3 H z, 1H) , 7.28 (d, J = 3. 3 H z, 1H ), 9. 22 ( s, 1H ), 9. 30 ( br s, 1H) .

LC /M S : condi ti on 3, r etent ion t im e = 1. 20 m in LC /M S (E SI ) m /z; 341 [ M+H ] H -N MR ( CD C l ) δ: 0 .31- 0.49 (m, 4 H) , 1.54- 1.98 (m , 7H) , 2.09- 2.42 ( m, 3H ), 2. 78 ( d, J = 6.6 Hz, 2H ) , 3.36- 3.44 (m , 1H ), 6. 78 ( d, J = 406 3. 0 H z, 1H ), 7. 29 ( d, J = 3. 0 H z, 1H ) , 9.23 (s, 1H ) , 9.27 (br s, 1H ) .

LC /M S : condi ti on 3, r etent ion t im e = 1. 29 m in LC /M S (E SI ) m /z; 311 [ M+H ] H -N MR ( D MS O- d ) δ : 1.21- 1.38 (m , 2H) , 1.70- 1.83 (m , 4H ), 1. 91-2. 07 ( m, 3H ), 3. 08-3. 19 ( m, 1H ), 3. 33 (dd, J = 18.4, 7. 8 H z, 2H ), 4. 11 ( s, 1H ), 4. 20-4. 27 ( m, 3H ), 6 .79-6. 83 ( m, 1H ) , 7.49 ( q, J 407 = 2. 5 H z, 1H ), 9. 51 ( s, 1H ), 12. 52 ( br s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 3. 60 m in LC /M S (E SI ) m /z; 420 [ M+H ] LC /M S (E SI ) m / z; 418 [ M- H] H -N MR ( D MS O- d ) δ : 1.21- 1.36 (m , 2H) , 1.69- 1.90 (m , 5H ), 1. 98-2. 07 ( m, 2H ), 3. 08-3. 19 ( m, 1H ), 3. 26-3. 34 (m, 2H ) , 4.18 (s, 2H ), 4. 43 ( s, 2H ), 6. 78-6. 83 ( m, 1H ), 7 .49-7. 52 ( m, 1H ) , 9.52 ( s, 408 1H ), 12. 54 (br s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 3. 09 m in LC /M S (E SI ) m /z; 377 [ M+H ] LC /M S (E SI ) m / z; 375 [ M- H] TABLE 146 E x D ata H -N MR ( D MS O- d ) δ : 0.81- 0.89 (m , 4H) , 1.17- 1.30 (m , 2H ), 1. 70-1. 89 ( m, 5H ), 1. 98-2. 07 ( m, 2H ), 2. 74-2. 81 (m, 1H ) , 3.10-3. 20 ( m, 1H ), 3. 25 ( d, J = 7.6 Hz, 2H ) , 4.16 (s, 2H ) , 6.81- 6.85 (m , 1H ), 409 7. 47-7. 52 ( m, 1H ), 9. 52 ( s, 1H ), 12. 53 ( br s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 3. 38 m in LC /M S (E SI ) m /z; 378 [ M+H ] LC /M S (E SI ) m / z; 376 [ M- H] LC /M S : condi ti on 1, r etent ion t im e = 3. 72 m in 410 LC /M S (E SI ) m /z; 432 [ M+H ] LC /M S (E SI ) m / z; 430 [ M- H] H -N MR ( D MS O- d ) δ : 1.13- 1.38 (m , 2H) , 1.70- 1.85 (m , 4H ), 1. 89-2. 06 ( m, 4H ), 3. 08-3. 21 ( m, 1H ), 3. 21-3. 32 (m, 1H ) , 3.38 (d, J = 7. 3 H z, 2H ), 3. 76-3. 89 ( m, 1H ), 4 .21- 4. 32 ( m, 1 H) , 6.80- 6.84 (m , 411 1H ), 7. 47-7. 52 (m, 1H ), 9. 52 (s, 1H ), 12. 53 ( br s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 3. 97 m in LC /M S (E SI ) m /z; 463 [ M+H ] LC /M S (E SI ) m / z; 461 [ M- H] H -N MR ( D MS O- d ) δ : 1.22- 1.41 (m , 2H) , 1.69- 1.96 (m , 5H ), 1. 98-2. 08 ( m, 2H ), 3. 10-3. 22 ( m, 1H ), 3. 37 (d, J = 7.3 Hz, 2H) , 3. 71-3. 86 ( m, 2H ), 4. 44 ( s, 2H ), 6. 79-6. 82 ( m, 1H ), 7. 48-7. 53 ( m, 412 1H ), 9. 53 ( s, 1H ), 12. 54 ( br s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 3. 54 m in LC /M S (E SI ) m /z; 420 [ M+H ] LC /M S (E SI ) m / z; 418 [ M- H] H -N MR ( CD C l ) δ: 0 .15 (m , 2H ) , 0.55 (m , 2H ), 0. 90 (m , 1H ), 1. 48 ( m, 2H ), 1. 90-2. 04 ( m, 4H ) , 2.18 (m, 2H) , 2.61 (d, J = 6.0 H z, 2H ), 2. 97 ( m, 1H ), 3. 12 ( m, 1H ) , 3.18 (q, J = 9.6 H z, 2H) , 6.79 ( d, J = 413 3. 3 H z, 1H ), 7. 30 ( m, 1H ) , 9.22 (s, 1H ), 9. 29 ( br s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 3. 85 m in LC /M S (E SI ) m /z; 393 [ M+H ] LC /M S (E SI ) m / z; 391 [ M- H] H -N MR ( D MS O- d ) δ : 0.12- 0.19 (m , 2H) , 0.48- 0.55 (m , 2H ), 0. 78-0. 90 ( m, 1H ), 1. 08-1. 25 ( m, 2H ), 1. 69-2. 05 (m, 6H ) , 2.33-2. 39 ( m, 5H ), 3. 09-3. 21 ( m, 1H ) , 3.87 (s, 2H ), 6. 83-6. 86 ( m, 1 H) , 7.49 (t , 414 J = 3.0 H z, 1 H) , 9.51 (s , 1H) , 12.52 (br s , 1H) .

LC /M S : condi ti on 1, r etent ion t im e = 3. 74 m in LC /M S (E SI ) m /z; 364 [ M+H ] LC /M S (E SI ) m / z; 362 [ M- H] H -N MR ( D MS O- d ) δ : 0.10- 0.16 (m , 2H) , 0.44- 0.52 (m , 2H ), 0. 83-0. 94 ( m, 1H ), 1. 05-1. 21 ( m, 2H ), 1. 54-1. 68 (m, 1H ) , 1.68-1. 84 ( m, 2H ), 1. 92-2. 06 ( m, 4H ) , 2.44- 2.58 (m , 4H) , 3.09- 3.21 (m , 1H ), 3. 25-3. 39 ( m, 2H ), 6. 80-6. 84 ( m, 1H ), 7. 47-7. 51 (m, 1H ) , 9.51 (s, 1H ), 12. 52 (br s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 4. 45 m in LC /M S (E SI ) m /z; 407 [ M+H ] LC /M S (E SI ) m / z; 405 [ M- H] TABLE 147 E x D ata H -N MR ( D MS O- d ) δ : 1.16- 1.28 (m , 3H) , 1.67- 1.88 (m , 3H ), 1. 93-2. 01 ( m, 2H ), 2. 11-2. 19 ( m, 2H ), 2. 40 (d, J = 5.7 Hz, 2H) , 3.10 ( tt , J = 11. 9, 3. 7 H z, 1H ), 6. 77-6. 80 ( m, 1H ), 7. 48 (t, J = 2. 9 Hz, 416 1H ), 9. 50 ( s, 1H ), 12. 50 ( br s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 2. 75 m in LC /M S (E SI ) m /z; 336 [ M+H ] LC /M S (E SI ) m / z; 334 [ M- H] LC /M S : condi ti on 1, r etent ion t im e = 3. 30 m in 417 LC /M S (E SI ) m /z; 375 [ M+H ] LC /M S (E SI ) m / z; 373 [ M- H] H -N MR ( D MS O- d ) δ : 1.39 (qd, J = 12. 6, 3.0 Hz, 2H ) , 1.72- 1.87 ( m, 2H ), 1. 97-2. 15 ( m, 4H ) , 2.71- 2.80 (m , 1H) , 2.79 (s, 6 H) , 2.99 ( d, J = 6. 6 H z, 2H ), 3.15 (t t, J = 12.2 , 3.3 H z, 1H) , 6.81 (dd, J = 3. 3, 2.0 H z, 1H) , 7. 50 ( t, J = 3.0 H z, 1H ), 9. 52 ( s, 1H ), 12. 54 ( br s , 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 3. 30 m in LC /M S (E SI ) m /z; 363 [ M+H ] LC /M S (E SI ) m / z; 361 [ M- H] LC /M S : condi ti on 1, r etent ion t im e = 3. 13 m in 419 LC /M S (E SI ) m /z; 374 [ M+H ] LC /M S (E SI ) m / z; 372 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 1. 89 m in 420 LC /M S (E SI ) m /z; 417 [ M+H ] LC /M S (E SI ) m / z; 415 [ M- H] H -N MR ( CD C l ) δ: 1 .07- 1.30 (m, 2 H) , 1.80- 2.04 (m , 4H) , 2.06- 2.19 ( m, 2H ), 2. 44 ( d, J = 6.6 Hz, 2H ) , 2.92- 3.04 (m , 2H ), 3. 07-3.19 (m , 1H ), 3. 67-3. 78 (m, 2H ), 3. 76 (d, J = 8.3 H z, 1H) , 3.82 (d, J = 8. 3 421 H z, 1H ), 4. 20-4. 32 ( m, 1H ), 6 .75- 6.80 ( m, 1H ) , 7.23- 7.29 (m , 1H) , 9. 10 ( br s, 1H ), 9. 20 ( s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 1. 52 m in LC /M S (E SI ) m /z; 409 [ M+H ] H -N MR ( CD C l ) δ: 1 .12- 1.30 (m, 3 H) , 1.51 (s, 3H ), 1 .84- 2.18 (m , 7H ), 2. 43 ( d, J = 6.9 H z, 2H) , 3.06 (d, J = 8. 3 H z, 2H ), 3. 09-3. 20 ( m, 1H ), 3. 35 ( d, J = 8.3 Hz, 2H ) , 6.75- 6.81 (m , 1H ), 7. 22-7.29 (m , 1H ), 9. 13 ( br s, 1H ), 9. 21 ( s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 1. 12 m in LC /M S (E SI ) m /z; 341 [ M+H ] H -N MR ( D MS O- d ) δ : 1.08- 1.24 (m , 2H) , 1.35- 1.50 (m , 1H ), 1. 65-1. 81 ( m, 2H ), 1. 83-2. 01 ( m, 4H ), 2. 00 (s, 6H ), 2. 29 ( d, J = 6 .6 H z, 2H ), 2. 68-2. 75 ( m, 3H ), 3 .11 (t t, J = 12.6, 3. 6 Hz, 1H ), 3. 37-3. 42 ( m, 2H ), 6. 79 ( d, J = 3. 3 H z, 1 H) , 7.47 (d, J = 3.3 H z, 1H ), 9. 49 ( s, 1H ), 12. 55 ( br s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 0. 34 m in LC /M S (E SI ) m /z; 354 [ M+H ] LC /M S (E SI ) m / z; 352 [ M- H] TABLE 148 E x D ata H -N MR ( D MS O- d ) δ : 0.94 (t , J = 7. 3 H z, 3H ), 1. 15 (qd, J = 12.6, 2. 6 H z, 2H ), 1. 36-1. 50 ( m, 1H ), 1. 73 (qd, J = 12. 6, 2. 6 H z, 2H ), 1. 84-2. 03 ( m, 4H ), 1. 98 ( s, 3H ), 2. 20 ( q, J = 7. 3 H z, 2H ), 2 .29 (d, J = 6. 6 H z, 2H ), 2. 69 ( t, J = 6. 9 H z, 2H ), 2. 81-2. 92 ( m, 1H ) , 3. 11 ( tt , 424 J = 11.6, 3. 3 H z, 1H ), 3. 43 ( t, J = 6. 9 H z, 2H ), 6. 80 (d, J = 3.3 H z, 1H ), 7. 48 ( d, J = 3.3 H z, 1H) , 9.51 (s, 1H) , 12.53 (br s , 1H) .

LC /M S : condi ti on 1, r etent ion t im e = 0. 34 m in LC /M S (E SI ) m /z; 368 [ M+H ] LC /M S (E SI ) m / z; 366 [ M- H] H -N MR ( D MS O- d ) δ : 1.05- 1.27 (m , 2H) , 1.27- 1.45 (m , 1H ), 1. 54-1. 82 ( m, 2H ), 1. 83-2. 04 ( m, 4H ), 2. 38 (d, J = 6.6 Hz, 1H) , 3. 03-3. 12 ( m, 1H ), 3. 13 ( d, J = 9. 5 H z, 2 H) , 3.55 (d, J = 9.5 H z, 2H ), 6. 80 ( dd, J = 3.0, 2. 1 H z, 2H ), 6. 82 (s, 1H ), 7. 47 ( t, J = 3. 0 H z, 1H ), 9. 50 ( s, 1H ), 12. 50 ( s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 1. 32 m in LC /M S (E SI ) m /z; 395 [ M+H ] LC /M S (E SI ) m / z; 393 [ M- H] LC /M S : condi ti on 3, r etent ion t im e = 1. 42 m in 426 LC /M S (E SI ) m /z; 436 [ M+H ] LC /M S (E SI ) m / z; 434 [ M- H] H -N MR ( D MS O- d ) δ : 1.10- 1.30 (m , 2H) , 1.49- 1.64 (m , 1H ), 1. 66-1. 84 ( m, 2H ), 1. 86-2. 08 ( m, 4H ), 2. 82-2. 93 (m, 5H ) , 3.06-3. 22 ( m, 1H ), 6. 80 ( dd, J = 3. 0, 2. 1 H z, 1H ), 7. 01 (t, J = 6. 3 H z, 1H ), 427 7. 48 ( t, J = 3.0 H z, 1H ), 9. 51 ( s, 1H ), 12. 5 ( s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 1. 57 m in LC /M S (E SI ) m /z; 349 [ M+H ] LC /M S (E SI ) m / z; 347 [ M- H] H -N MR ( D MS O- d ) δ : 1.09- 1.28 (m , 2H) , 1.40 (s, 9H ), 1.64- 1.85 ( m, 2H ), 1. 87-2. 07 ( m, 5H ) , 2.39- 2.57 (m , 2H) , 3.05- 3.26 (m , 1H ), 3. 57 ( brs, 2H ), 4.32 ( d, J = 10.2H z, 2H ), 4. 62 ( d, J = 10.2 Hz, 2H ) , 6. 93 ( d, J = 3. 3 H z, 1 H) , 7.75 (d, J = 3. 3 H z, 1H ), 9. 62 ( s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 2. 09 m in LC /M S (E SI ) m /z; 465 [ M+H ] H -N MR ( D MS O- d ) δ : 1.40- 1.59 (m , 2H) , 1.71- 2.10 (m , 6H ), 2. 26-2. 40 ( m, 1H ), 3. 09-3. 26 ( m, 1H ), 6. 80-6. 87 (m, 1H ) , 6.54 (d, J = 6. 8 H z, 0.2H ) , 7.31 (d, J = 4. 8 H z, 0. 8H) , 9.5 1 (s , 1H) , 10. 4 (s, 0. 8H) , 10.7 (s , 0.2H ), 12. 51 ( s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 1. 51 m in LC /M S (E SI ) m /z; 271 [ M+H ] H -N MR ( CD C l ) δ: 1 .76- 2.06 (m, 4 H) , 2.16- 2.28 (m , 2H) , 2.30- 2.41 ( m, 2H ), 2. 58-2. 73 ( m, 1H ) , 3.17- 3.30 (m , 1H) , 6.75 (dd, J = 3.3, 1. 8 H z, 1H ), 7. 31 ( t, J = 3. 3 H z, 1H ), 9. 15 ( br s, 1H ), 9. 22 ( s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 1. 68 m in LC /M S (E SI ) m /z; 267 [ M+H ] LC /M S (E SI ) m / z; 265 [ M- H] TABLE 149 E x D ata H -N MR ( CD C l ) δ: 1 .48- 1.65 (m, 2 H) , 1.95- 2.13 (m , 4H) , 2.19- 2.33 ( m, 2H ), 2. 85-3. 02 ( m, 1H ) , 3.15- 3.29 (m , 1H) , 6.76 (dd, J = 3.3, 2. 1 H z, 1H ), 7. 23 ( d, J = 10. 4 H z, 1H ) , 7.31 (t , J = 3. 3 Hz, 1H ) , 431 9. 20 ( br s, 1H ), 9. 23 ( s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 1. 99 m in LC /M S (E SI ) m /z; 318 [ M+H ] LC /M S (E SI ) m / z; 316 [ M- H] H -N MR ( D MS O- d ) δ : 1.21- 1.39 (m , 2H) , 1.54- 1.67 (m , 1H ), 1. 68-1. 86 ( m, 2H ), 1. 87-2. 11 ( m, 6H ), 3. 08-3. 22 (m, 1H ) , 4.92 (t, J = 7. 4 H z, 1H ), 6. 80 ( dd, J = 3. 0, 1. 8 H z, 1H ), 7 .49 (t , J = 3. 0 Hz, 432 1H ), 9. 51 ( s, 1H ), 12. 51 ( s, 1H ).

LC /M S : condi ti on 3, r etent ion t im e = 1. 93 m in LC /M S (E SI ) m /z; 320 [ M+H ] LC /M S (E SI ) m / z; 318 [ M- H] H -N MR ( D MS O- d ) δ : 1.70- 1.90 (m , 2H) , 2.00- 2.18 (m , 2H ), 2. 23-2. 80 ( m, 4H ), 3. 20-3. 50 ( m, 1H ), 4. 72 (s, 2H ), 6. 81 ( d, J = 2 .7 H z, 1H ), 7. 49 ( d, J = 1. 8 Hz, 1H ), 9 .51 (s, 1H ) , 12.52 (br s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 3. 79 m in LC /M S (E SI ) m /z; 254 [ M+H ] LC /M S (E SI ) m / z; 252 [ M- H] H -N MR ( CD C l ) δ: 2 .13 (m , 2H ) , 2.30 (m , 2H ), 2. 45 (m , 2H ), 2. 68 ( m, 1H ), 3. 13 ( m, 1H ) , 3.50 (t t, J = 11. 4, 3.9 H z, 1H) , 5.21 (s, 1H ) , 6. 77 ( t, J = 3.0 H z, 1H ), 7. 34 ( t, J = 3.0 H z, 1H ), 9. 25 ( s, 1H ), 9. 38 434 ( br s, 1H) .

LC /M S : condi ti on 1, r etent ion t im e = 3. 37 m in LC /M S (E SI ) m /z; 279 [ M+H ] LC /M S (E SI ) m / z; 277 [ M- H] H -N MR ( CD C l ) δ: 1 .86 (m , 4H ) , 1.96 (m , 2H ), 2. 09 (m , 1H ), 2. 19 ( m, 2H ), 2. 42 ( d, J = 7.5 Hz, 2H ) , 3.46 (m , 1H ), 6. 75 ( t, J = 3.0 H z, 435 1H ), 7. 30 ( t, J = 3. 0 H z, 1H ), 9. 23 ( s, 1H ), 9. 25 ( br s, 1H ). a LC /M S : condi ti on 1, r etent ion t im e = 3. 38 m in LC /M S (E SI ) m /z; 281 [ M+H ] LC /M S (E SI ) m / z; 279 [ M- H] H -N MR ( CD C l ) δ: 1 .43 (m , 2H ) , 1.84- 2.01 (m , 3H) , 2.05 -2.26 (m , 2H ), 2. 20 ( m, 2H ) , 2.41 (m , 2H) , 3.18 (t t, J = 12, 3. 6 H z, 1H ), 6. 78 435 ( m, 1H ), 7. 31 ( m, 1H ) , 9.23 (s, 1H ), 9. 47 (br s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 3. 27 m in LC /M S (E SI ) m /z; 281 [ M+H ] LC /M S (E SI ) m / z; 279 [ M- H] H -N MR ( CD C l ) δ: 1 .31 (t , 3H) , 2.03- 2.32 (m , 5H ), 2. 40-2. 58 (m , 2H ), 3. 50 ( tt , J = 11.1, 3. 6 H z, 1H ), 3. 96 (m , 1H) , 4.2 0 (q , J = 6. 9 H z, 2H ), 5. 76 ( s, 1H ), 6. 78 ( dd, J = 3. 3, 2. 1 H z, 1H ), 7. 33 ( t, J = 436 3. 3 H z, 1H ), 9. 26 ( s, 1H ), 10. 02 ( br s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 3. 80 m in LC /M S (E SI ) m /z; 326 [ M+H ] LC /M S (E SI ) m / z; 324 [ M- H] TABLE 150 E x D ata H -N MR ( CD C l ) δ: 1 .97 (s, 3H ), 2. 00-2. 28 ( m, 5H ) , 2.44 (m, 1H ) , 2. 90 ( m, 1H ), 3. 13 ( m, 1H ) , 3.48 (t t, J = 10. 8, 3.9 Hz, 1H ) , 6.76 (m , 1H ), 7. 31 ( m, 1H ) , 9.17 (br s, 1H ), 9. 23 (s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 3. 54 m in LC /M S (E SI ) m /z; 293 [ M+H ] LC /M S (E SI ) m / z; 291 [ M- H] H -N MR ( CD C l ) δ: 1 .28 (m , 6H ) , 1.75 (m , 4H ), 1. 81-2. 02 (m , 8H ), 2. 13-2. 32 ( m, 8H ), 2. 43 (d, J = 7.2 H z, 2H ), 3. 17 ( tt , J = 11.7, 3. 6 H z, 1H ), 3. 39 ( m, 1H ), 4. 16 (m , 4H ) , 6.78 (m , 2H) , 7.32 (m , 2H ) , 438 9. 25 ( s, 1H ), 9. 26 ( s, 1H ), 10. 00 ( br s, 2H) .

LC /M S : condi ti on 1, r etent ion t im e = 3. 80 m in (ci s/ tr ans m ix tur e) LC /M S (E SI ) m /z; 328 [ M+H ] LC /M S (E SI ) m / z; 326 [ M- H] H -N MR ( CD C l ) δ: 1 .34 (d, J = 7.2 H z, 3H ), 1. 42-1. 61 (m , 5H ), 1. 80 ( m, 2H ), 1. 93 ( m, 2H ) , 2.68 (qui n, J = 7. 2 H z, 1H ), 3. 51 (m , 439 1H ), 6. 76 ( m, 1H ) , 7.29 (m , 1H) , 9.23 (s, 1H ) . a LC /M S : condi ti on 1, r etent ion t im e = 3. 65 m in LC /M S (E SI ) m /z; 295 [ M+H ] LC /M S (E SI ) m / z; 293 [ M- H] H -N MR ( CD C l ) δ: 1 .40 (m , 3H ) , 1.42- 1.61 (m , 5H ), 1. 97 ( m , 2H) , 2. 20 ( m, 2H ), 2. 65 ( qui n, J = 6. 6 H z, 1H ), 3. 19 ( m, 1H ) , 6.79 (m , 439 1H ), 7. 31 ( m, 1H ) , 9.15 (br s, 1H ), 9. 23 (s, 1H ). b LC /M S : condi ti on 1, r etent ion t im e = 3. 49 m in LC /M S (E SI ) m /z; 295 [ M+H ] LC /M S (E SI ) m / z; 293 [ M- H] H -N MR ( CD C l ) δ: 1 .42 (m , 2H ) , 1.91- 2.04 (m , 4H) , 2.20 (m , 2H) , 2. 36 ( m, 1H ), 3. 16 ( tt , J = 12.0, 3. 6 H z, 1H ), 5.37 (dd, J = 16.5 , 1.5 H z, 1H ), 6. 76 ( dd, J = 16. 5, 6.9 H z, 1H ), 6. 77 ( d, J = 3 .3, 1H ), 7.29 440 ( d, J = 3. 3 H z, 1H ), 9.16 (br s, 1H ), 9. 22 (s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 3. 54 m in LC /M S (E SI ) m /z; 293 [ M+H ] LC /M S (E SI ) m / z; 291 [ M- H] H -N MR ( CD C l ) δ: 1 .24 (m , 2H ) , 1.59- 1.73 (m , 5H) , 1.87 -2.04 (m , 2H ), 2. 16 ( m, 2H ) , 2.44( t, J = 7.2 H z, 2H ) , 3.17 (t t, J = 12. 3, 3.3 H z, 1H ), 6. 78 ( dd, J = 3. 3, 2.1, 1H) , 7.30 (t , J = 3.3 H z, 1H ), 9. 22 441 ( s, 1H) , 9.2 8 (b r s , 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 3. 47 m in LC /M S (E SI ) m /z; 295 [ M+H ] LC /M S (E SI ) m / z; 293 [ M- H] H -N MR ( CD C l ) δ: 1 .74 (m , 4H ) , 1.91- 2.17 (m , 6H) , 2.31 (m , 1H) , 3. 40 ( m, 1H ), 3. 93 ( m, 2H ) , 6.77 (m , 1H) , 7.25 (m , 1H ), 9. 12 ( br s, 442 1H ), 9. 22 ( s, 1H ). a LC /M S : condi ti on 1, r etent ion t im e = 3. 42 m in LC /M S (E SI ) m /z; 381 [ M+H ] LC /M S (E SI ) m / z; 379 [ M- H] TABLE 151 E x D ata H -N MR ( CD C l ) δ: 1 .74 (m , 2H ) , 1.98 (m , 4H ), 2. 13 (m , 3H ), 2. 25 ( m, 2H ), 3. 17 ( m, 1H ) , 3.96 (m , 2H) , 6.78 (m , 1H) , 7.28 (m , 1H ), 442 9. 07 ( br s, 1H ), 9. 21 ( s, 1H ). b LC /M S : condi ti on 1, r etent ion t im e = 3. 30 m in LC /M S (E SI ) m /z; 381 [ M+H ] LC /M S (E SI ) m / z; 379 [ M- H] H -N MR ( CD O D) δ: 1. 75 ( m, 4H ) , 1.94 ( m, 3 H) , 2.10- 2.30 (m , 4H) , 3. 39 ( m, 1H ), 4. 15 ( s, 2H ), 6. 80 ( d, J = 3.3 Hz, 1H ) , 7.38 (d, J = 3.3 443 H z, 1H ), 9. 29 ( s, 1H ). a LC /M S : condi ti on 1, r etent ion t im e = 3. 04 m in LC /M S (E SI ) m /z; 338 [ M+H ] LC /M S (E SI ) m / z; 336 [ M- H] H -N MR ( CD O D) δ: 1. 75-2. 33 ( m, 11H ), 3. 54 ( m, 1H ) , 4.16 (s, 2H ), 6. 83 ( d, J = 3. 3 H z, 1 H) , 7.40 (d, J = 3. 3 H z, 1H ), 9. 29 ( s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 2. 85 m in LC /M S (E SI ) m /z; 338 [ M+H ] LC /M S (E SI ) m / z; 336 [ M- H] H -N MR ( CD C l ) δ: 1 .13 (m , 3H ) , 1.33 (m , 2H ), 2. 13 (m , 6H ), 3. 19 ( m, 1H ), 6. 83 ( d, J = 3.3 Hz, 1H ) , 7.33 (d, J = 3.3 H z, 1H ), 9. 24 ( s, 1H ), 9. 35 ( br s, 1H ).

LC /M S : condi ti on 1, r etent ion t im e = 3. 32 m in LC /M S (E SI ) m /z; 293 [ M+H ] LC /M S (E SI ) m / z; 291 [ M- H] H -N MR ( D MS O- d ) δ : 1.60- 1.80 (m , 6H) , 1.99- 2.11 (m , 6H ), 2. 26-2. 32 ( m, 2H ), 4. 60 ( s, 1H ), 6. 83 ( dd, J = 3. 0, 1.7 H z, 1H ), 7. 52 ( t, J = 3.0 H z, 1H ), 9. 54 ( s, 1H ), 12. 58 ( br s, 1H) .

LC /M S : condi ti on 1, r etent ion t im e = 3. 10 m in LC /M S (E SI ) m /z; 310 [ M+H ] LC /M S (E SI ) m / z; 308 [ M- H] Pharmacological assay Now, a pharmacological assay of the tricyclic pyrimidine compounds of the present invention will be described.

ASSAY EXAMPLE 1. Enzyme assay JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd.(PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl , 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 µM, and the plate was incubated at room temperature for 2 hours.

After addition of a termination reagent containing EDTA (ehylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS. From the plot of logarithm of a compound concentration and inhibitory activity, the IC was calculated. The results of JAK3, JAK1, JAK2 and Tyk2 enzyme assays of the compounds of Synthetic Examples are shown in Tables 152 to 155. “*” in the Tables indicates IC > 1 µM.

TABLE 152 Ex .

TABLE 153 Ex .

TABLE 154 Ex .

TABLE 155 Ex .

The tricyclic pyrimidine compounds of the present invention have favorable inhibitory activity against JAKs as shown above.

ASSAY EXAMPLE 2. Signal assay in human whole blood To be a effective pharmaceutical compound for the target diseases of the present invention, especially for rheumatoid arthritis, it is more favorable that the compounds indicate excellent inhibitory activity against JAKs in human whole blood. Inhibitory activity against JAKs in human whole blood can be assessed by, for example, STAT phosphorylation assay in human whole blood as described below.

Compounds are added at the various concentrations to human whole blood which is collected from healthy volunteers and preincubated for 30 minutes. Next, cytokine such as IL-2 or IL-6 is added to the mixture and incubated for 15 minutes. Cytokines can be purchased, for example, from PeproTech Inc. Cytokines are added to mixture at 100 ng/mL as final concentration. The mixture including the blood cells are hemolyzed, fixed, permeabilized, washed, and resuspended in stain buffer. BD Cytofix/Cytoperm® solution (manufactured by Becton, Dickinson and Company (BD)), for example, can be used to hemolyze, fix, and permeabilize. Staining buffer (manufactured by BD), for example, can be used as stain buffer according to each protocol issued by BD. Fluorescence-labeled anti-phosphorylated STAT antibody and fluorescence-labeled anti-CD3 antibody are added to the cell suspension and incubated for 30 minutes. Then, cells are washed and resuspended in stain buffer.

Fluorescence-labeled anti-phosphorylated STAT antibody and fluorescence-labeled anti-CD3 antibody can be purchased, for example from BD, and final concentration of antibodies can be determined according to each protocols issued by BD.

Fluorescence intensity of fluorescence-labeled cells in cell suspension is detected by flow-cytometory. Because the detected fluorescence intensity is proportional to the concentration of the phosphorylated STAT protein in CD3 positive cells, inhibitory activity against STAT phosphorylation by the compounds can be calculated from the ratio between the above mentioned fluorescence intensity and the blank fluorescence intensity which is measured simultaneously without the compounds. From the plot of logarithm of the compound concentrations and the inhibitory activities, the IC value can be calculated.

ASSAY EXAMPLE 3. Inhibition of proliferation of erythro-leukemic cell line The inhibitory activity of the tricyclic pyrimidine compounds of the present invention on cell proliferation mediated by JAK signal can be assayed using a human erythro-leukemic cell line, TF-1.

TF-1 cells can be purchased from ATCC (American Type Culture Collection). TF- 1 cells can be expanded in RPMI1640 media containing 5% FBS and 1 ng/mL GM-CSF (Granulocyte Macrophage Colony-Stimulating Factor) using a CO incubator (5% CO , 37°C). At the assay, TF-1 cells washed by PBS (Phosphate Buffered Saline) are resuspended in RPMI1640 media containing 5% FBS, and dispensed in 96-well culture plate at 1 x 10 cells/well. Compounds at various concentrations are added to the cells and preincubated for 30 minutes, and then cytokine such as IL-4 or IL-6 is added to the cells. Culture plates are incubated using a CO incubator (5% CO , 37°C) for 3 days.

Cell proliferation can be assayed using WST-8 reagent (Kishida Chemical Co., Ltd.) 40 according to instructions by the manufacturer. The formazan pigment is generated by the addition of WST-8 reagent solution to each well of the culture plates and the subsequent incubation in a CO incubator (5% CO , 37°C) for 4 hours, and then detected by measuring the absorbance at 450 nm with a microplate reader. From the plot of logarithm of the compound concentrations and the inhibitory activities, the IC 45 value can be calculated.

REFERENCE SYNTHETIC EXAMPLE 1 Methyl 4-methylpyridinylcarbamate Potassium tert-butoxide (10.3 g, 92.5 mmol) in tetrahydrofuran (25 mL) was stirred at 23 to 27°C for 30 minutes, and dimethyl carbonate (4.67 mL, 55.5 mmol) was added while the temperature was kept at 35°C or below. To the reaction mixture, 3-amino methylpyridine (5.00 g, 46.2 mmol) in tetrahydrofuran (40 mL) stirred at 32 to 38°C for 90 minutes was added dropwise at 20 to 35°C over 2 hours with stirring. The resulting reaction mixture was cooled to 15 to 20°C , stirred with water (25 mL) at 25°C or below for 1 hour and extracted with tetrahydrofuran. The organic layer was azeotropically distilled with toluene under reduced pressure to a volume of about 50 mL and stirred at 23 to 27°C for one day. The precipitated solid was collected by filtration, washed with toluene and dried under reduced pressure to give the title compound as a brown solid (6.77 g, yield 88%).

REFERENCE SYNTHETIC EXAMPLE 2 Methyl rac-(3R,4R)benzylmethylpiperidinylcarbamate Methyl 4-methylpyridinylcarbamate (30.6 g, 184 mmol) and 5% rhodium– carbon (12 g) in acetic acid (120 mL) were stirred at 72 to 78°C under a hydrogen atmosphere (70-80 psi). After disappearance of the starting materials was confirmed by NMR, the reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give a concentrate (40.9 g). The concentrate (31.7 g) was stirred with benzaldehyde (21.5 mL, 202 mmol) in toluene (184 mL) at 20 to 30°C for 30 minutes. The resulting toluene solution was added dropwise at 30°C or below to a toluene (40 mL) solution of sodium triacetoxyborohydride (9.35 g, 44.0 mmol) stirred at to 30°C for 1 hour. The resulting reaction mixture was stirred for 2 hours, adjusted to pH 6-7 with 3 M aqueous sodium hydroxide at 20°C to 30°C and extracted with toluene. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give a brown oil (38.1 g) containing the title compound. The oil was used for the next step without further purification.

REFERENCE SYNTHETIC EXAMPLE 3 rac-(3R,4R)Benzylmethylpiperidinamine Crude methyl rac-(3R,4R)benzylmethylpiperidinylcarbamate (2.3 g) in concentrated hydrochloric acid (15 mL) was refluxed for one day under heating and allowed to cool to room temperature. The hydrochloric acid was removed under reduced pressure, and the reaction mixture was partitioned between chloroform and saturated aqueous sodium chloride. The aqueous layer was basified with saturated aqueous sodium carbonate and extracted with ethyl acetate twice, and the organic layers were combined, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting brown oil (4.94 g) containing the title compound was used for the next step without further purification. 40 REFERENCE SYNTHETIC EXAMPLE 4 1H-Pyrrolo[2,3-b]pyridine 7-oxide m-Chloroperbenzoic acid (25 wt% water content, 12.7 g, 55.2 mmol) in ethyl acetate (30 mL) was gradually added dropwise to 1H-pyrrolo[2,3-b]pyridine (5.14 g, 43.5 mmol) in ethyl acetate (45 mL) cooled to 0°C, and the reaction mixture was stirred 45 at room temperature for one day and then stirred with m-chloroperbenzoic acid (25 wt% water content, 3.93 g, 17.1 mmol) in ethyl acetate (4 mL) at room temperature for 4 hours. The reaction mixture was cooled with ice and filtered, and the resulting solid was purified by silica gel column chromatography (silica gel NH type manufactured by Fuji Silysia Chemical Ltd.: chloroform / methanol = 10/1 (v/v)) to give the title compound as a yellow solid (4.95 g, yield 85%).

REFERENCE SYNTHETIC EXAMPLE 5 4-Chloro-1H-pyrrolo[2,3-b]pyridine 1H-Pyrrolo[2,3-b]pyridine 7-oxide (4.95 g, 36.9 mmol) in N,N-dimethylformamide (10 mL) was heated to 50°C, mixed with methanesulfonyl chloride (8.00 mL, 103 mmol) and stirred at 73°C for 3 hours. The reaction mixture was cooled with ice and diluted with water (70 mL), neutralized with sodium hydroxide and stirred for 10 minutes under cooling with ice. The precipitated solid was collected by filtration, washed with water and dried under reduced pressure to give the title compound as a reddish brown solid (4.65 g, yield 83%).

REFERENCE SYNTHETIC EXAMPLE 6 4-Chloro(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine 4-Chloro-1H-pyrrolo[2,3-b]pyridine (2.84 g, 18.6 mmol) in N,N-dimethylformamide (10 mL) and tetrahydrofuran (10 mL) was stirred with sodium hydride (55 wt% dispersion in mineral oil, 1.08 g, 27.0 mmol) under cooling with ice for 1 hour. The reaction mixture was stirred with triisopropylsilyl chloride (6.0 mL, 28 mmol) at room temperature for one day. After addition of water, the reaction mixture was warmed to room temperature and extracted with hexane twice. The resulting organic layers were combined, washed with saturated aqueous sodium chloride dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane) to give the title compound as a reddish brown oil (5.74 mg, yield 99%).

REFERENCE SYNTHETIC EXAMPLE 7 4-Chloro-1H-pyrrolo[2,3-b]pyridinecarbaldehyde s-Butyllithium - hexane/cyclohexane solution (1.06 M, 27 mL, 29 mmol) was added to 4-chloro(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (5.74 g, 18.6 mmol) in tetrahydrofuran (50 mL) cooled to -78°C, and the reaction mixture was stirred for 1 hour.

The reaction mixture was stirred with N,N-dimethylformamide (7.0 mL, 90 mmol) for another 1 hour and then with 4 M hydrogen chloride - 1,4-dioxane solution (20 mL) for minutes, and after addition of water, extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane (15 mL) and stirred with trifluoroacetic acid (15 mL) for one day.

The reaction mixture was concentrated under reduced pressure, diluted with water and neutralized with saturated aqueous sodium hydrogen carbonate, and the residue was collected by filtration and dried under reduced pressure. The crude product was mixed with ethyl acetate (20 mL) and hexane (20 mL), and the solid was collected by filtration, washed with hexane and dried under reduced pressure to give the title compound as a 40 pale yellow solid (2.72 g, yield 81%).

REFERENCE SYNTHETIC EXAMPLE 8 4-(Cyclohexylamino)-1H-pyrrolo[2,3-b]pyridinecarbaldehyde 4-Chloro-1H-pyrrolo[2,3-b]pyridinecarbaldehyde (845 mg, 4.68 mmol) and cyclohexylamine (2.5 mL, 22 mmol) in ethylene glycol (2 mL) were stirred at 170°C for 1 45 hour under microwave irradiation. The reaction mixture was allowed to cool to room temperature and, after addition of water, extracted with chloroform. The organic layer was stirred with 2 M hydrochloric acid (20 mL) for 1 hour, and the organic layer was separated. The aqueous layer was adjusted to pH 9 or above with 10 M aqueous sodium hydroxide and extracted with chloroform. The organic layers were combined, washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform / methanol = 10/1 (v/v)) to give the title compound as a pale yellow oil (804 mg, yield 71%).

REFERENCE SYNTHETIC EXAMPLE 9 4-(Cyclohexylamino){[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine carbaldehyde 4-(Cyclohexylamino)-1H-pyrrolo[2,3-b]pyridinecarbaldehyde (273 mg, 1.12 mmol) in N,N-dimethylformamide (3 mL) was stirred with sodium hydride (55 wt% dispersion in mineral oil, 61.2 mg, 1.53 mmol) for 1 hour under cooling with ice. The reaction mixture was stirred with [2-(chloromethoxy)ethyl]trimethylsilane (260 µL, 1.47 mmol) at room temperature for one day, and after addition of water, extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane/ ethyl acetate = 5/1 (v/v)) to give the title compound as a pale yellow oil (265 mg, yield 63%).

REFERENCE SYNTHETIC EXAMPLE 10 (4-(Cyclohexylamino){[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinyl) methanol 4-(Cyclohexylamino){[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine- -carbaldehyde (104 mg, 0.279 mmol) in methanol (3 mL) was stirred with sodium borohydride (15.8 mg, 0.418 mmol) at room temperature for 2 hours, after addition of water, the reaction mixture was extracted with chloroform twice, and the organic layers were combined, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting pale yellow oil containing the title compound was used for the next step without further purification.

REFERENCE SYNTHETIC EXAMPLE 11 1-Cyclohexyl{[2-(trimethylsilyl)ethoxy]methyl}-1,2,4,7- tetrahydropyrrolo[3’,2’:5,6]pyrido[4,3-d][1,3]oxazine [4-(Cyclohexylamino){[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin- -yl)methanol (38 mg, 0.10 mmol) and aqueous formaldehyde (35 wt%, 0.6 mL, 8 mmol) in ethanol (2 mL) were stirred at 75°C for 1 hour. The reaction mixture was then stirred with acetic acid (1 mL) at 75°C for 1 hour, allowed to cool to room temperature, and after addition of saturated aqueous sodium hydrogen carbonate, extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 2/1 (v/v)) to give the title compound as a colorless oil (19.8 mg, yield 51%). 40 REFERENCE SYNTHETIC EXAMPLE 12 -(Aminomethyl)-N-cyclohexyl{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- b]pyridinamine (4-(Cyclohexylamino){[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin- -yl)methanol (870 mg, 2,31 mmol) obtained in Reference Synthetic Example 10, 45 phthalimide (681 mg, 4.63 mmol) and triphenylphosphine (1.21, 4.63 mmol) in tetrahydrofuran (10 mL) were stirred at room temperature for 30 minutes and then stirred with diisopropyl azodicarboxylate (936 mg, 4.63 mmol) for one day. The reaction mixture was concentrated under reduced pressure, and after addition of water, extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ ethyl acetate = 10/1 (v/v)) to remove triphenylphosphine oxide. The resulting crude product was dissolved in ethanol (30 mL) and stirred with hydrazine monohydrate (1.0 mL, 12 mmol) at 80°C for 1 hour and allowed to cool to room temperature. The precipitated solid was collected by filtration and washed with ethanol and chloroform. The filtrate and the washings were combined and concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform / methanol = 20/1 (v/v) to give the title compound as a colorless oil (513 mg, yield 59%).

REFERENCE SYNTHETIC EXAMPLE 13 1-Cyclohexyl{[2-(trimethylsilyl)ethoxy]methyl}-3,4-dihydro-1H- pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidin-2(7H)-one -(Aminomethyl)-N-cyclohexyl{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- b]pyridinamine (127 mg, 0.339 mmol) in dichloromethane was stirred with 1,1’- carbonyldiimidazole (65.9 mg, 0.407 mmol) at 60°C for 2 hours. The reaction mixture was concentrated under reduced pressure and, after addition of water, extracted with chloroform. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give the title compound as a colorless oil (93.2 mg, yield 69%).

REFERENCE SYNTHETIC EXAMPLE 14 1-Cyclohexyl-1,4-dihydro{[2-(trimethylsilyl)ethoxy]methyl}-pyrrolo[3’,2’:5,6]pyrido[3,4- e]pyrimidine -(Aminomethyl)-N-cyclohexyl{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- b]pyridinamine (104 mg, 0.278 mmol) obtained in Reference Synthetic Example 12 in ethyl orthoformate (1 mL) was reacted at 180°C for 30 minutes under microwave irradiation and allowed to cool to room temperature. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (Hi Flash column amino type manufactured by Yamazen Corporation: hexane/ ethyl acetate = 1/1 (v/v) to give the title compound as a pale yellow oil (48.8 mg, yield 45%).

REFERENCE SYNTHETIC EXAMPLE 15 2,3-Dihydro-1H-pyrrolo[2,3-b]pyridine 1H-Pyrrolo[2,3-b]pyridine (8.78 g, 74.3 mmol) and 5% palladium-carbon in a mixture of triethylamine (5 mL) and formic acid (30 mL) was stirred at 80°C for 4 days.

The reaction mixture was allowed to cool to room temperature and filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was adjusted to pH 12 with 6 M aqueous sodium hydroxide and stirred at 65°C for 5 hours. The 40 reaction mixture was allowed to cool to room temperature and extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1/2 → ethyl acetate / methanol = 20/1 (v/v)) to give the title compound as a pale yellow solid (2.15 g, yield 24%). 45 REFERENCE SYNTHETIC EXAMPLE 16 -Bromo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine 2,3-Dihydro-1H-pyrrolo[2,3-b]pyridine (4.40 g, 36.6 mmol) in a mixture of pyridine (4.4 mL) and dichloromethane (20 mL) was gradually added dropwise to bromine (7.00 g, 43.8 mmol) in dichloromethane (20 mL) cooled to 0°C, and the resulting reaction mixture was stirred at 0°C for 20 minutes, after addition of saturated aqueous sodium thiosulfate, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure.

The residue was purified by silica gel column chromatography (hexane/ ethyl acetate = 1/1 → 0/1 (v/v)) to give the title compound as a brown solid (2.83 g, yield 39%).

REFERENCE SYNTHETIC EXAMPLE 17 -Bromo-1H-pyrrolo[2,3-b]pyridine -Bromo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine (2.83 g, 14.2 mol) and manganese dioxide (5.0 g, 58 mmol) in chloroform (30 mL) were stirred at 65°C for 3 hours. The reaction mixture was allowed to cool to room temperature and filtered, and the solid was washed with chloroform, and the filtrate and the washings were combined and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ ethyl acetate / chloroform = 2/1/1 →1/1/0 (v/v/v)) to give the title compound as a brown solid (2.14 g, yield 76%).

REFERENCE SYNTHETIC EXAMPLE 18 -Bromo-1H-pyrrolo[2,3-b]pyridine 7-oxide m-Chloroperbenzoic acid (25 wt% water content, 322 mg, 1.40 mmol) in ethyl acetate (5 mL) was gradually added dropwise to 5-bromo-1H-pyrrolo[2,3-b]pyridine (184 mg, 0.934 mmol) in ethyl acetate (10 mL), and the reaction mixture was stirred at room temperature for 6 hours. After addition of saturated aqueous sodium hydrogen carbonate, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure.

The residue was mixed with a mixture of ethyl acetate / hexane = 1/1 (v/v), and the solid was collected by filtration, washed with hexane and dried under reduced pressure to give the title compound as a light brown solid (150 mg, yield 75%).

REFERENCE SYNTHETIC EXAMPLE 19 -Bromochloro{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine -Bromo-1H-pyrrolo[2,3-b]pyridine 7-oxide (150 mg, 0.704 mmol) in N,N- dimethylformamide (2 mL) was heated to 50°C and stirred with methanesulfonyl chloride (58 µL, 0.75 mmol) at 70°C for 2 hours and allowed to cool to room temperature. After addition of saturated aqueous sodium chloride, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in N,N-dimethylformamide (2 mL), cooled to 0°C, mixed with sodium hydride (55 wt% dispersion in mineral oil, 45 mg, 1.03 mmol) and [2- (chloromethoxy)ethyl]trimethylsilane (186 µL, 1.05 mmol) and stirred at room temperature for 3 hours. After addition of saturated aqueous sodium chloride, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over 40 anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 20/1 (v/v)) to give the title compound as a pale yellow oil (158 mg, yield 62%).

REFERENCE SYNTHETIC EXAMPLE 20 -Bromo-N-cyclohexyl{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin 45 amine -Bromochloro{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine (150 mg, 0.415 mmol) and cyclohexylamine (1 mL, 9 mmol) in ethylene glycol (1 mL) were stirred at 200°C for 2 hour under microwave irradiation. The reaction mixture was allowed to cool to room temperature and, after addition of saturated aqueous sodium chloride, extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ ethyl acetate = 10/1 (v/v)) to give the title compound as an orange oil (141 mg, yield 80%).

REFERENCE SYNTHETIC EXAMPLE 21 1-(4-(Cyclohexylamino){[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin yl)ethanone -Bromo-N-cyclohexyl{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin- 4-amine (160 mg, 0.377 mmol) in toluene (3 mL) was stirred with bis(triphenylphosphine)palladium (II) dichloride (35 mg, 0.050 mmol) and tributyl(1- ethoxyvinyl)tin (382 µL, 1.13 mmol) at 75°C for 3 hours. The reaction mixture was allowed to cool to room temperature and stirred with 1 M hydrochloric acid (2 mL) and potassium fluoride (100 mg, 1.73 mmol) at room temperature for 30 minutes. The reaction mixture was filtered, and the solid was washed with ethyl acetate. The filtrate and the washings were mixed with water and extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 20/1 → 5/1 (v/v)) to give the title compound as a yellow oil (58 mg, yield 40%).

REFERENCE SYNTHETIC EXAMPLE 22 1-(4-(Cyclohexylamino){[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin yl)ethanol 1-(4-(Cyclohexylamino){[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- b]pyridinyl)ethanone (13 mg, 0.034 mmol) in methanol (1 mL) was stirred with sodium borohydride (30 mg, 0.79 mmol) at room temperature for 1 hour and at 60°C for another 5 hours. The reaction mixture was allowed to cool to room temperature and, after addition of water, extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 4/1 → 3/1 (v/v)) to give the title compound as a colorless oil (9.1 mg, yield 70%).

REFERENCE SYNTHETIC EXAMPLE 23 1-Cyclohexylmethyl{[2-(trimethylsilyl)ethoxy]methyl}-1,2,4,7- tetrahydropyrrolo[3’,2’:5,6]pyrido[4,3-d][1,3]oxazine 1-(4-(Cyclohexylamino){[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- b]pyridinyl)ethanol (9 mg, 0.02 mmol) and aqueous formaldehyde (35 wt%, 0.3 mL, 4 mmol) in ethanol (1 mL) were stirred at 75°C for 1 hour. The reaction mixture was allowed to cool to room temperature and, after addition of water, extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated 40 under reduced pressure. The resulting pale yellow oil (9 mg) containing the title compound was used for the next step without further purification.

REFERENCE SYNTHETIC EXAMPLE 24 1-Cyclohexyl{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-h][1,6]naphthyridin- 4(7H)-one 45 1-(4-(Cyclohexylamino){[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- b]pyridinyl)ethanone (25 mg, 0.065 mmol) obtained in Reference Synthetic Example 21 in N,N-dimethylformamide dimethyl acetal (0.5 mL) was stirred at 180°C for 3 hours under microwave irradiation. The reaction mixture was allowed to cool to room temperature and concentrated under reduced pressure, and the resulting residue was dissolved in tetrahydrofuran (1 mL) and stirred with 1 M hydrochloric acid (1 mL) at 80°C for 1 hour. The reaction mixture was allowed to cool to room temperature and, after addition of saturated aqueous sodium hydrogen carbonate, extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate / methanol = 1/1/0 → 0/10/1 (v/v/v)) to give the title compound as a colorless oil (13.6 mg, yield 53%).

REFERENCE SYNTHETIC EXAMPLE 25 4-Chloro(methylsulfonyl)(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine s-Butyllithium - hexane/cyclohexane solution (1.06 M, 0.700 mL, 0.742 mmol) was gradually added dropwise to 4-chloro(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (100 mg, 0.324 mmol) obtained in Reference Synthetic Example 6 in tetrahydrofuran (1 mL) cooled to -78°C, and the reaction mixture was stirred at -78°C for 30 minutes and stirred with dimethyl disulfide (30 µL, 0.33 mmol) at -78°C for 30 minutes. After addition of 1 M aqueous sodium hydroxide, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in ethanol (2 mL) and stirred with ammonium molybdate tetrahydrate (40 mg, 0.032 mmol) and aqueous hydrogen peroxide (30 wt%, 132 µL, 1.29 mmol) at room temperature for 5 hours. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure.

The residue was purified by silica gel column chromatography (hexane / ethyl acetate = /1 → 5/1 (v/v)) to give the title compound as a pale yellow oil (61.4 mg, yield 49%).

REFERENCE SYNTHETIC EXAMPLE 26 N-Cyclohexyl(methylsulfonyl)-1H-pyrrolo[2,3-b]pyridinamine 4-Chloro(methylsulfonyl)(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (61 mg, 0.16 mmol) in cyclohexylamine (200 µL, 1.74 mmol) was stirred with N,N- diisopropylethylamine (40 µL, 0.23 mmol) at 120°C for 30 minutes The reaction mixture was allowed to cool to room temperature and, after addition of water, extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate =20/1 → 5/1 (v/v)) to give the title compound as a colorless solid (7.0 mg, yield 15%).

REFERENCE SYNTHETIC EXAMPLE 27 N-Cyclohexyl(methylsulfonyl){[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- b]pyridinamine N-Cyclohexyl(methylsulfonyl)-1H-pyrrolo[2,3-b]pyridinamine (7.0 mg, 0.024 mmol) in N,N-dimethylformamide (1 mL) was stirred with sodium hydride (55 wt% 40 dispersion in mineral oil, 3.0 mg, 0.069 mmol) and [2- (chloromethoxy)ethyl]trimethylsilane (10 µL, 0.057 mmol) at room temperature for 2 hours. After addition of saturated aqueous sodium chloride, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica 45 gel column chromatography (hexane / ethyl acetate = 10/1 → 3/1 (v/v)) to give the title compound as a colorless oil (6.1 mg, yield 60%).

REFERENCE SYNTHETIC EXAMPLE 28 1-Cyclohexyl{[2-(trimethylsilyl)ethoxy]methyl}-1,4-dihydropyrrolo[3’,2’:5,6]pyrido[3,4- b][1,4]thiazine-4,4(7H)-dione N-Cyclohexyl(methylsulfonyl){[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- b]pyridinamine (6.1 mg, 0.014 mmol) in N,N-dimethylformamide dimethyl acetal (2.5 mL) was stirred at 170°C for 3 hours under microwave irradiation. The reaction mixture was allowed to cool to room temperature and concentrated under reduced pressure. The resulting residue was dissolved in tetrahydrofuran (1 mL) and stirred with 1 M hydrochloric acid (1 mL) at 80°C for 1 hour. The reaction mixture was allowed to cool to room temperature and, after addition of water, extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting pale yellow oil (8.5 mg) containing the title compound was used for the next step without further purification.

REFERENCE SYNTHETIC EXAMPLE 29 4-(Cyclohexylamino){[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine carboxylic acid 4-(Cyclohexylamino){[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine- -carbaldehyde (380 mg, 1.02 mmol) obtained in Reference Synthetic Example 9 in acetic acid (4 mL) was stirred with sulphamic acid (150 mg, 1.54 mmol) and 2-methyl butene (500 µL, 4.71 mmol) under cooling with ice, and then sodium chlorite (100 mg, 1.11 mmol) in water (0.5 mL) was added dropwise, and the resulting reaction mixture was stirred at room temperature for 1 hour. Sodium chlorite (30 mg, 0.33 mmol) in water (0.3 mL) was further added dropwise, and the resulting reaction mixture was stirred for 1 hour. After addition of water, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 3/1 → 0/1 (v/v)) to give the title compound as a pale yellow oil (207 mg, yield 52%).

REFERENCE SYNTHETIC EXAMPLE 30 4-(Cyclohexylamino){[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine carboxamide 4-(Cyclohexylamino){[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine- -carboxylic acid (100 mg, 0.257 mmol) in dichloromethane (2 mL) was stirred with 1-(3- dimethylaminopropyl)ethylcarbodiimide hydrochloride (10 mg, 0.052 mmol), N- hydroxybenzotriazole (50 mg, 0.37 mmol) and 7 M ammonia - methanol solution (0.2 mL, 1.4 mmol) at room temperature for one day. After addition of saturated aqueous ammonium chloride, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1/1 → 0/1 (v/v)) to give the title compound as a pale yellow amorphous (71.1 mg, yield 71%). 40 REFERENCE SYNTHETIC EXAMPLE 31 4-(Cyclohexylamino)-N-formyl{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- b]pyridinecarboxamide 4-(Cyclohexylamino){[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine- -carboxamide (45 mg, 0.12 mmol) in triethyl orthoformate (2 mL) was stirred at 120°C 45 for one day. The reaction mixture was allowed to cool to room temperature and concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane / ethyl acetate = 3/1 → 0/1 (v/v)) to give the title compound as a pale yellow amorphous (12.4 mg, yield 27%).

REFERENCE SYNTHETIC EXAMPLE 32 1-Cyclohexyl{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[3',2':5,6]pyrido[4,3- d]pyrimidin-4(7H)-one 4-(Cyclohexylamino)-N-formyl{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- b]pyridinecarboxamide (12.4 mg, 0.0311 mmol) in N-methylpyrrolidinone (0.5 mL) was stirred at 200°C for 30 minutes under microwave irradiation. The reaction mixture was allowed to cool to room temperature and, after addition of saturated aqueous ammonium chloride, extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1/1 (v/v)) to give the title compound as a pale yellow amorphous (9.2 mg, yield 74%).

REFERENCE SYNTHETIC EXAMPLE 33 1-(4-Chloro{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinyl)ethanone -Bromochloro{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine (47 mg, 0.13 mmol) obtained in Reference Synthetic Example 19 in toluene (1 mL) was stirred with bis(triphenylphosphine)palladium (II) dichloride (10 mg, 0.014 mmol) and tributyl(1-ethoxyvinyl)tin (50 µL, 0.15 mmol) at 120°C for 4 hours. The reaction mixture was allowed to cool to room temperature and stirred with water (2 mL) and potassium fluoride (100 mg, 1.73 mmol) at room temperature for 1 hour. The reaction mixture was filtered, and the solid was washed with ethyl acetate. The filtrate and the washings were mixed with water and extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was stirred with hydrogen chloride - methanol solution (10 wt%, 0.1 mL) at room temperature for 10 minutes. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane / ethyl acetate = 10/1 → 2/1 (v/v)) to give the title compound as a pale yellow oil (20 mg, yield 47%).

REFERENCE SYNTHETIC EXAMPLE 34 rac(4-{[(3R,4R)Benzylmethylpiperidinyl]amino}{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinyl)ethanone 1-(4-Chloro{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin yl)ethanone (15 mg, 0.46 mmol) and rac-(3R,4R)benzylmethylpiperidinamine (34 mg, 0.17 mmol) obtained in Reference Synthetic Example 3 in ethylene glycol (3 mL) was stirred with N,N-diisopropylethylamine (10 µL, 0.057 mmol) at 200°C for 1 hour under microwave irradiation. The reaction mixture was allowed to cool to room temperature and stirred with methanol (2 mL) and 1 M hydrochloric acid (1 mL) at 50°C for 30 minutes. The reaction mixture was allowed to cool to room temperature and, after addition of saturated aqueous sodium hydrogen carbonate, extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column 40 chromatography (hexane / ethyl acetate = 10/1 → 4/1 (v/v)) to give the title compound as a yellow oil (7.0 mg, yield 31%).

REFERENCE SYNTHETIC EXAMPLE 35 rac[(3R,4R)Benzylmethylpiperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one 45 rac(4-{[(3R,4R)Benzylmethylpiperidinyl]amino}{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinyl)ethanone (20 mg, 0.041 mmol) in N,N-dimethylformamide dimethyl acetal (1 mL) was stirred at 170°C for 6 hours under microwave irradiation. The reaction mixture was allowed to cool to room temperature and concentrated under reduced pressure, and the resulting residue was dissolved in tetrahydrofuran (1 mL) and stirred with 1 M hydrochloric acid (1 mL) at 80°C for 1 hour. The reaction mixture was allowed to cool to room temperature and, after addition of saturated aqueous sodium hydrogen carbonate, extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate / methanol = 1/1/0 → 0/5/1 (v/v/v)) to give the title compound as a yellow oil (6.1 mg, yield 30%).

REFERENCE SYNTHETIC EXAMPLE 36 rac[(3R,4R)Methylpiperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- h][1,6]naphthyridin-4(7H)-one rac[(3R,4R)Benzylmethylpiperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}- 1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one (98 mg, 0.20 mmol) and 5% palladium- carbon (65 mg) in methanol (2 mL) were stirred at room temperature for 2 hours under a hydrogen atmosphere, then at 40°C for 5 hours and at room temperature for one day.

The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give the title compound as a pale yellow amorphous (76.8 mg, yield 95%).

REFERENCE SYNTHETIC EXAMPLE 37 rac[(3R,4R)(Isobutylsulfonyl)methylpiperidinyl]{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one rac[(3R,4R)Methylpiperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one (23 mg, 0.056 mmol) in dichloromethane (2 mL) was mixed with N,N-diisopropylethylamine (30 µL, 0.17 mmol) and 2- methylpropanesulfonyl chloride (12 µL, 0.092 mmol) under cooling with ice and stirred at room temperature for 2 hours. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate / methanol = 1/1/0 → 0/10/1 (v/v/v)) to give the title compound as a pale pink solid (18.3 mg, yield 62%).

REFERENCE SYNTHETIC EXAMPLE 38 rac{[(3R,4R)Benzylmethylpiperidinyl]amino}-1H-pyrrolo[2,3-b]pyridine carbaldehyde 4-Chloro-1H-pyrrolo[2,3-b]pyridinecarbaldehyde (247 mg, 1.36 mmol) obtained in Reference Synthetic Example 7 and rac-(3R,4R)benzylmethylpiperidinamine (700 mg, 3,42 mmol) obtained in Reference Synthetic Example 3 in ethylene glycol (3 mL) were stirred at 180°C for 3 hours under microwave irradiation. The reaction mixture was allowed to cool to room temperature and, after addition of water and 1 M aqueous sodium hydroxide, extracted with chloroform, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The 40 resulting residue was stirred with 1,4-dioxane (5 mL), 4 M hydrogen chloride - 1,4- dioxane solution (10 mL) and water (2 mL) at room temperature for one day. The reaction mixture was concentrated under reduced pressure, adjusted to pH 9 or above with 1M aqueous sodium hydroxide and extracted with chloroform and water, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under 45 reduced pressure. The residue was purified by silica gel column chromatography (Hi Flash column amino type manufactured by Yamazen Corporation: hexane / ethyl acetate = 1/1 (v/v)) to give the title compound as a brown oil (154 mg, yield 33%).

REFERENCE SYNTHETIC EXAMPLE 39 rac{[(3R,4R)Benzylmethylpiperidinyl]amino}{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinecarbaldehyde rac{[(3R,4R)Benzylmethylpiperidinyl]amino}-1H-pyrrolo[2,3-b]pyridine- -carbaldehyde (118 mg, 0.338 mmol) in N,N-dimethylformamide (3 mL) was cooled to 0°C and stirred with sodium hydride (55 wt% dispersion in mineral oil, 126 mg, 0.586 mmol) for 30 minutes and then with [2-(chloromethoxy)ethyl]trimethylsilane (104 µL. 0.586 mmol) at room temperature for one day. After addition of water, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1/1 (v/v)) to give the title compound as a brown oil (67.5 mg, yield 42%).

REFERENCE SYNTHETIC EXAMPLE 40 rac-(4-{[(3R,4R)Benzylmethylpiperidinyl]amino}{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinyl)methanol rac{[(3R,4R)Benzylmethylpiperidinyl]amino}{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinecarbaldehyde (112 mg, 0.234 mmol) in methanol was stirred with sodium borohydride (13.3 mg, 0.351 mmol) at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure and, after addition of water, extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Hi Flash column amino type manufactured by Yamazen Corporation: hexane / ethyl acetate = 1/1 (v/v)) to give the title compound as a colorless oil (55 mg, yield 49%).

REFERENCE SYNTHETIC EXAMPLE 41 rac[(3R,4R)Benzylmethylpiperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}- 1,2,4,7-tetrahydropyrrolo[3’,2’:5,6]pyrido[4,3-d][1,3]oxazine rac-(4-{[(3R,4R)Benzylmethylpiperidinyl]amino}{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinyl)methanol (55 mg, 0.11 mmol) was stirred with formic acid (2 mL) and acetic acid (200 µL) at 75°C for 4 hours. The reaction mixture was concentrated under reduced pressure and, after addition of water, extracted with chloroform, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 2/1 (v/v)) to give the title compound (34.3 mg, yield 61%).

REFERENCE SYNTHETIC EXAMPLE 42 6-Bromo-3H-imidazo[4,5-b]pyridine 2,3-Diaminobromopyridine (4.10 g, 21.8 mmol) in formic acid (25 mL) was stirred at 100°C for 4 hours. The reaction mixture was allowed to cool to room temperature and concentrated under reduced pressure, and the resulting residue was 40 mixed with water and adjusted to pH 8 or above with saturated aqueous sodium hydrogen carbonate. The precipitated solid was collected by filtration, washed with water and chloroform and dried under reduced pressure to give the title compound as a dark brown solid (4.13 g, yield 96%).

REFERENCE SYNTHETIC EXAMPLE 43 45 6-Bromo-3H-imidazo[4,5-b]pyridine 4-oxide m-Chloroperbenzoic acid (25 wt% water content, 2.77 g, 12.0 mmol) was gradually added dropwise to 6-bromo-3H-imidazo[4,5-b]pyridine (1.58 mg, 7.98 mmol) in ethyl acetate (15 mL), and the reaction mixture was stirred at room temperature for one day. The precipitated solid was collected by filtration and washed with ethyl acetate and diethyl ether and dried under reduced pressure to give the title compound as a pale yellow solid (1.67 g, yield 98%).

REFERENCE SYNTHETIC EXAMPLE 44 6-Bromochloro-3H-imidazo[4,5-b]pyridine 6-Bromo-3H-imidazo[4,5-b]pyridine 4-oxide (1.88 g, 8.82 mmol) in N,N- dimethylformamide (12 mL) was heated to 50°C, mixed with methansulfonyl chloride (8.00 mL, 103 mmol) and stirred at 73°C for 3 hours. The reaction mixture was cooled with ice and gradually poured into saturated aqueous sodium hydrogen carbonate (75 mL), and the precipitated solid was collected by filtration, washed with water and chloroform and dried under reduced pressure to give the title compound as a dark brown solid (1.07 g, yield 52%).

REFERENCE SYNTHETIC EXAMPLE 45 6-Bromochloro{[2-(trimethylsilyl)ethoxy]methyl}-3H-imidazo[4,5-b]pyridine 6-Bromochloro-3H-imidazo[4,5-b]pyridine (1.07 g, 4.60 mmol) in N,N- dimethylformamide (12 mL) was cooled to 0°C, mixed with sodium hydride (55 wt% dispersion in mineral oil, 300 mg, 6.88 mmol) and [2- (chloromethoxy)ethyl]trimethylsilane (12.0 mL, 6.78 mmol) and stirred at room temperature for 3 hours. After addition of saturated aqueous sodium chloride, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane / ethyl acetate = 10/1 → 5/1 (v/v)) to give the title compound as a yellow oil (640 mg, yield 38%).

REFERENCE SYNTHETIC EXAMPLE 46 1-(7-Chloro{[2-(trimethylsilyl)ethoxy]methyl}-3H-imidazo[4,5-b]pyridinyl)ethanone 6-Bromochloro{[2-(trimethylsilyl)ethoxy]methyl}-3H-imidazo[4,5-b]pyridine (379 mg, 1.05 mmol) in toluene (6 mL) was stirred with bis(triphenylphosphine)palladium(II) dichloride (106 mg, 0.151 mmol) and tributyl(1- ethoxyvinyl)tin (435 mg, 1.21 mmol) at 120°C 4 hours. The reaction mixture was allowed to cool to room temperature and stirred with water (20 mL) and potassium fluoride (0.5 g) at room temperature for 1 hour. The reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was stirred with hydrogen chloride - methanol solution (10 wt%, 4 mL) at room temperature for 10 minutes. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane / ethyl acetate = 5/1 → 3/1 (v/v)) to give the title compound as a yellow solid (89.6 mg, yield 26%).

REFERENCE SYNTHETIC EXAMPLE 47 40 1-[7-(Cyclohexylamino){[2-(trimethylsilyl)ethoxy]methyl}-3H-imidazo[4,5-b]pyridin yl]ethanone 1-[7-Chloro{[2-(trimethylsilyl)ethoxy]methyl}-3H-imidazo[4,5-b]pyridin yl]ethanone (89.6 mg, 0.275 mmol) and cyclohexylamine (214 mg, 2.16 mmol) in ethylene glycol (2 mL) were stirred at 180°C for 1 hour under microwave irradiation. 45 The reaction mixture was allowed to cool to room temperature and, after addition of saturated aqueous sodium chloride, extracted with chloroform. The organic layer was stirred with 2 M hydrochloric acid (12 mL) at room temperature for 1 hour. The reaction mixture was basified with 10 M aqueous sodium hydroxide and extracted with chloroform, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure.

The residue was purified by silica gel column chromatography hexane / ethyl acetate = 1/1 (v/v)) to give the title compound as a dark brown oil (88.9 mg, yield 83%).

REFERENCE SYNTHETIC EXAMPLE 48 9-Cyclohexyl{[2-(trimethylsilyl)ethoxy]methyl}-3H-imidazo[4,5-h][1,6]naphthyridin- 6(9H)-one 1-[7-(Cyclohexylamino){[2-(trimethylsilyl)ethoxy]methyl}-3H-imidazo[4,5- b]pyridinyl]ethanone (88.9 mg, 0.229 mmol) in N,N-dimethylformamide dimethyl acetal (2.0 mL) was stirred at 180°C for 5 hours. The reaction mixture was allowed to cool to room temperature and concentrated under reduced pressure, and the resulting residue was dissolved in tetrahydrofuran (5 mL) and stirred with 1 M hydrochloric acid (2 mL) at 80°C for 1 hour. The reaction mixture was allowed to cool to room temperature and, after addition of saturated aqueous sodium hydrogen carbonate, extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate / methanol = 1/1/0 → 0/10/1 (v/v/v)) to give the title compound as a yellow solid (57.5 mg, yield 63%).

REFERENCE SYNTHETIC EXAMPLE 49 1-(3-Bromochloro{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin yl)ethanone 1-(4-Chloro{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin yl)ethanone (91 mg, 0.28 mmol) obtained in Reference Synthetic Example 33 in dichloromethane (3 mL) was mixed with N-bromosuccinimide (75 mg, 0.42 mmol) under cooling with ice and stirred at room temperature for 2 hours. After addition of saturated aqueous sodium thiosulfate, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 5/1 (v/v)) to give the title compound as a colorless oil (61.0 mg, yield 54%).

REFERENCE SYNTHETIC EXAMPLE 50 rac(4-{[(3R,4R)Benzylmethylpiperidinyl]amino}bromo{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinyl)ethanone 1-(3-Bromochloro{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin yl)ethanone (61 mg, 0.15 mmol) was stirred with rac-(3R,4R)Benzyl methylpiperidinamine (85 mg, 0.42 mmol) obtained in Reference Synthetic Example 3 and N,N-diisopropylethylamine (50 µL, 0.29 mmol) at 130°C for 5 hours. The reaction mixture was allowed to cool to room temperature and purified by silica gel column chromatography (hexane / ethyl acetate = 10/1 (v/v)) to give the title compound 40 as a pale yellow oil (28.7 mg, yield 33%).

REFERENCE SYNTHETIC EXAMPLE 51 rac[(3R,4R)Benzylmethylpiperidinyl]bromo{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-h][1,6]naphthyridin(7H)-one The reactions in Reference Synthetic Example 35 were carried out in 45 substantially the same manners except that rac(4-{[(3R,4R)benzyl methylpiperidinyl]amino}bromo{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- b]pyridinyl)ethanone was used instead of rac(4-{[(3R,4R)benzyl methylpiperidinyl]amino}{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin- -yl)ethanone to give the title compound as a colorless oil (12.3 mg, yield 45%).

REFERENCE SYNTHETIC EXAMPLE 52 1-(3,4-Dichloro{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin yl)ethanone 1-(4-Chloro{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin yl)ethanone (80 mg, 0.25 mmol) obtained in Reference Synthetic Example 33 in N,N- dimethylformamide (2 mL) was stirred with N-chlorosuccinimide (66 mg, 0.49 mmol) at 80°C for 3 hours. The reaction mixture was allowed to cool to room temperature and, after addition of saturated aqueous sodium chloride, extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 10/1 → 5/1 (v/v)) to give the title compound as a colorless solid (23.8 mg, yield 27%).

REFERENCE SYNTHETIC EXAMPLE 53 rac(4-{[(3R,4R)Benzylmethylpiperidinyl]amino}chloro{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinyl)ethanone The reactions in Reference Synthetic Example 50 were carried out in substantially the same manners except that 1-(3,4-dichloro{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinyl)ethanone was used instead of 1-(3-bromochloro{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin yl)ethanone to give the title compound as a pale yellow oil (13.4 mg, yield 39%).

REFERENCE SYNTHETIC EXAMPLE 54 rac[(3R,4R)Benzylmethylpiperidinyl]chloro{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one The reactions in Reference Synthetic Example 35 were carried out in substantially the same manners except that rac(4-{[(3R,4R)benzyl methylpiperidinyl]amino}chloro{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- b]pyridinyl)ethanone was used instead of rac(4-{[(3R,4R)benzyl methylpiperidinyl]amino}{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin- 5-yl)ethanone to give the title compound as a colorless oil (5.6 mg, yield 42%).

REFERENCE SYNTHETIC EXAMPLE 55 4-Chloro{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinecarbaldehyde 4-Chloro-1H-pyrrolo[2,3-b]pyridinecarbaldehyde (550 mg, 3.05 mmol) obtained in Reference Synthetic Example 7 in N,N-dimethylformamide (5 mL) was stirred with sodium hydride (60 wt% dispersion in liquid paraffin, 150 mg, 3.75 mmol) for 10 minutes under cooling with ice and then stirred with [2-(chloromethoxy)ethyl]trimethylsilane (650 µL, 3.67 mmol) at room temperature for 30 minutes. After addition of saturated aqueous ammonium chloride, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride, dried over 40 anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 5/1 (v/v)) to give the title compound as a colorless solid (815 mg, yield 86%).

REFERENCE SYNTHETIC EXAMPLE 56 1-(4-Chloro{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinyl)propanol 45 4-Chloro{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine carbaldehyde (117 mg, 0.360 mmol) in tetrahydrofuran (2 mL) was mixed with ethylmagnesium bromide - tetrahydrofuran solution (1.0 M, 1.0 mL, 1.0 mmol) under cooling with ice and stirred at room temperature for one day. After addition of saturated aqueous ammonium chloride, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 4/1 (v/v)) to give the title compound as a colorless oil (75.6 mg, yield 62%).

REFERENCE SYNTHETIC EXAMPLE 57 1-(4-Chloro{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinyl)propan 1-(4-Chloro{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin yl)propanol (75.6 mg, 0.222 mmol) in 1,2-dimethoxyethane (5 mL) was vigorously stirred with manganese dioxide (450 mg, 5.17 mmol) at 60°C for 3 hours and then at 80°C for 3 hours. The reaction mixture was filtered, the solid was washed with chloroform, and the filtrate and the washings were concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 10/1 → 5/1 (v/v)) to give the title compound as a colorless oil (39.9 mg, yield 53%).

REFERENCE SYNTHETIC EXAMPLE 58 rac(4-{[(3R,4R)Benzylmethylpiperidinyl]amino}{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinyl)propanone The reactions in Reference Synthetic Example 50 were carried out in substantially the same manners except that 1-(4-chloro{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinyl)propanone was used instead of 1-(3-bromochloro{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- b]pyridinyl)ethanone to give the title compound as a pale yellow oil (40.1 mg, yield 71%).

REFERENCE SYNTHETIC EXAMPLE 59 rac[(3R,4R)Benzylmethylpiperidinyl]methyl{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one The reactions in Reference Synthetic Example 35 were carried out in substantially the same manners except that rac(4-{[(3R,4R)benzyl methylpiperidinyl]amino}{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin- -yl)propanone was used instead of rac(4-{[(3R,4R)benzylmethylpiperidin yl]amino}{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinyl)ethanone to give the title compound as a colorless oil (18.0 mg, yield 44%).

REFERENCE SYNTHETIC EXAMPLE 60 rac[(3R,4R)Benzylmethylpiperidinyl]bromo{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one rac[(3R,4R)Benzylmethylpiperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}- 1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one (70 mg, 0.14 mmol) obtained in Reference 40 Synthetic Example 35 in dichloromethane (5 mL) was mixed with N-bromosuccinimide (25 mg, 0.14 mmol) under cooling with ice and stirred at room temperature for one day and then with N-bromosuccinimide (8 mg, 0.04 mmol) for one day. After addition of saturated aqueous sodium hydrogen carbonate, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and 45 concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane /ethyl acetate = 5/1 → 2/1 (v/v)) to give a mixture (22.4 mg) containing the title compound. The mixture was used for the next step without further purification.

REFERENCE SYNTHETIC EXAMPLE 61 rac{[(3R,4R)Methyl(4-oxo{[2-(trimethylsilyl)ethoxy]methyl}-4,7-dihydro-1H- pyrrolo[2,3-h][1,6]naphthyridinyl)piperidinyl]sulfonyl}benzonitrile rac[(3R,4R)Methylpiperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one (20 mg, 0.049 mmol) obtained in Reference Synthetic Example 36 in dichloromethane (2 mL) was stirred with 2- cyanobenzenesulfonyl chloride (15 mg, 0.074 mmol) and N,N-diisopropylethylamine (20 µL, 0.11 mmol) at room temperature for 1 hour. The reaction mixture was purified by silica gel column chromatography (hexane / ethyl acetate / methanol = 1/1/0 → 0/10/1 (v/v/v)) to give the title compound as a colorless solid (24.5 mg, yield 87%).

REFERENCE SYNTHETIC EXAMPLES 62 TO 71 The reactions in Reference Synthetic Example 61 were carried out in substantially the same manners except that 3-cyanobenzensulfonyl chloride, ethyl chloroformate, 1-isocyanato(trifluoromethyl)benzene, 1-isocyanato (trifluoromethyl)benzene, 2-(trifluoromethyl)benzoyl chloride, 3-(trifluoromethyl)benzoyl chloride, 2-(4-fluorophenyl)acetyl chloride, 3-(trifluoromethyl)benzenesulfonyl chloride, 4-(trifluoromethyl)benzoyl chloride or benzyl chloroformate was used instead of 2- cyanobenzenesulfonyl chloride to give the compounds of Reference Synthetic Examples 62 to 71. The names, morphologies and yields of the compounds synthesized are shown in Tables 3 to 4.

TABLE 3 Rf Compound Name Morphology Yield rac{[(3R,4R)methyl(4-oxo {[2-(trimethylsilyl)ethoxy]met colorless 62 hyl}-4,7-dihydro-1H-pyrrolo[2,3-h 65% solid ][1,6]naphthyridinyl)piperidin yl]sulfonyl}benzonitrile rac-(3R,4R)-ethyl 4-methyl(4-oxo{[2-(trimethy colorless 63 lsilyl)ethoxy]methyl}-4,7-dihydro 85% -1H-pyrrolo[2,3-h][1,6]naphthyrid inyl)piperidinecarboxylate rac-(3R,4R)methyl(4-oxo{ [2-(trimethylsilyl)ethoxy]methyl} -4,7-dihydro-1H-pyrrolo[2,3-h][1, colorless 64 87% 6]naphthyridinyl)-N-[2-(triflu oil oromethyl)phenyl]piperidinecar boxamide rac-(3R,4R)methyl(4-oxo{ [2-(trimethylsilyl)ethoxy]methyl} -4,7-dihydro-1H-pyrrolo[2,3-h][1, colorless 65 98% 6]naphthyridinyl)-N-[3-(triflu oil oromethyl)phenyl]piperidinecar boxamide rac{(3R,4R)methyl[2-(tri fluoromethyl)benzoyl]piperidin colorless 66 yl}{[2-(trimethylsilyl)ethoxy] 94% methyl}-1H-pyrrolo[2,3-h][1,6]nap hthyridin-4(7H)-one rac{(3R,4R)methyl[3-(tri fluoromethyl)benzoyl]piperidin colorless 67 yl}{[2-(trimethylsilyl)ethoxy] 92% methyl}-1H-pyrrolo[2,3-h][1,6]nap hthyridin-4(7H)-one rac{(3R,4R)[2-(4-fluorophen yl)acetyl]methylpiperidinyl colorless 68 }{[2-(trimethylsilyl)ethoxy]me 80% thyl}-1H-pyrrolo[2,3-h][1,6]napht hyridin-4(7H)-one rac((3R,4R)methyl{[3-(tr ifluoromethyl)phenyl]sulfonyl}pip colorless 69 eridinyl){[2-(trimethylsily 78% l)ethoxy]methyl}-1H-pyrrolo[2,3-h ][1,6]naphthyridin-4(7H)-one rac{(3R,4R)methyl[4-(tri fluoromethyl)benzoyl]piperidin colorless 70 yl}{[2-(trimethylsilyl)ethoxy] 69% methyl}-1H-pyrrolo[2,3-h][1,6]nap hthyridin-4(7H)-one TABLE 4 Rf Compound Name Morphology Yield rac-(3R,4R)-benzyl 4-methyl(4-oxo{[2-(trimethy colorless 71 lsilyl)ethoxy]methyl}-4,7-dihydro 66% -1H-pyrrolo[2,3-h][1,6]naphthyrid inyl)piperidinecarboxylate REFERENCE SYNTHETIC EXAMPLE 72 Phenyl 1,3,4-thiadiazolylcarbamate 1,3,4-Thiadiazolamine (253 mg, 2.50 mmol) in N,N-dimethylacetamide (3 mL) was stirred with phenyl chloroformate (392 µL, 3.13 mmol) at room temperature for one day. Water was added to the reaction mixture, and the precipitated solid was collected by filtration, washed with water and hexane and dried under reduced pressure to give the title compound as a colorless solid (418 mg, yield 76%).

REFERENCE SYNTHETIC EXAMPLE 73 rac-(3R,4R)Methyl(4-oxo{[2-(trimethylsilyl)ethoxy]methyl}-4,7-dihydro-1H- pyrrolo[2,3-h][1,6]naphthyridinyl)-N-(1,3,4-thiadiazolyl)piperidinecarboxamide rac[(3R,4R)Methylpiperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one (30.2 mg, 0.0732 mmol) obtained in Reference Synthetic Example 36 in tetrahydrofuran (3 mL) was refluxed with phenyl 1,3,4-thiadizolylcarbamate (19.6 mg, 0.0886 mmol) and triethylamine (17.9 µL, 0.128 mmol) for 3 hours under heating. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate → chloroform / methanol = 10/1 (v/v)) to give the title compound as a pale yellow solid (44.0 mg, quantitative yield).

REFERENCE SYNTHETIC EXAMPLE 74 Phenyl (3-methylisothiazolyl)carbamate 3-Methylisothiazolamine (156 mg, 1.04 mmol) in pyridine (1.2 mL) was mixed with phenyl chloroformate (260 µL, 2.07 mmol) under cooling with ice and stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure, and after addition of water, extracted with chloroform twice, and the organic layer was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1/1 (v/v)) to give the title compound as a pale yellow solid (173 mg, yield 71%).

REFERENCE SYNTHETIC EXAMPLE 75 rac-(3R,4R)Methyl-N-(3-methylisothiazolyl)(4-oxo{[2- (trimethylsilyl)ethoxy]methyl}-4,7-dihydro-1H-pyrrolo[2,3-h][1,6]naphthyridin yl)piperidinecarboxamide rac[(3R,4R)Methylpiperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one (29.5 mg, 0.0715 mmol) obtained in Reference Synthetic Example 36 in tetrahydrofuran (3 mL) was refluxed with phenyl (3-methylthiazolyl)carbamate (21.2 mg, 0.0905 mmol) and triethylamine (17.5 µL, 0.125 mmol) for 3 hours under heating. The reaction mixture was concentrated under 40 reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate → chloroform / methanol = 10/1 (v/v)) to give the title compound as a yellow oil (38.4 mg, yield 97%).

REFERENCE SYNTHETIC EXAMPLE 76 rac[(3R,4R)(Cyclopentanecarbonyl)methylpiperidinyl]{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one rac[(3R,4R)Methylpiperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one (31.0 mg, 0.751 mmol) obtained in Reference Synthetic Example 36 and triethylamine (30.0 µL, 0.215 mmol) in tetrahydrofuran (4 mL) were stirred with cyclopentanecarbonyl chloride (20.0 µL, 0.165 mmol) at room temperature for one day. After addition of 1 M aqueous sodium hydroxide, the reaction mixture was extracted with chloroform, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform / methanol = 10/1 v/v)) to give the title compound as a pale yellow oil (44.5 mg, quantitative yield).

REFERENCE SYNTHETIC EXAMPLE 77 rac{(3R,4R)methyl[3-(trifluoromethyl)benzyl]piperidinyl}{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one rac[(3R,4R)Methylpiperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one (24.8 mg, 0.0601 mmol) obtained in Reference Synthetic Example 36 in tetrahydrofuran (4 mL) was stirred sodium hydride (55 wt% dispersion in mineral oil, 49.4 mg, 1.23 mmol) and 3-(trifluoromethyl)benzyl bromide (38.2 mg, 0.160 mmol) at room temperature for one day. After addition of water under cooling with ice, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate → chloroform / methanol = 20/1 (v/v)) to give the title compound as a pale yellow oil (26.8 mg, quantitative yield).

REFERENCE SYNTHETIC EXAMPLE 78 rac{(3R,4R)methyl[4-(trifluoromethyl)benzyl]piperidinyl}{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one The reactions in Reference Synthetic Example 77 were carried out in substantially the same manners except that 4-(trifluoromethyl)benzyl bromide was used instead of 3-(trifluoromethyl)benzyl bromide to give the title compound as a pale yellow oil (32.8 mg, quantitative yield).

REFERENCE SYNTHETIC EXAMPLE 79 rac{(3R,4R)methyl[2-(trifluoromethyl)benzyl]piperidinyl}{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one rac[(3R,4R)Methylpiperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}-1H- 40 pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one (13.4 mg, 0.0325 mmol) obtained in Reference Synthetic Example 36 in tetrahydrofuran (4 mL) was stirred with sodium hydride (55 wt% dispersion in mineral oil, 30.6 mg, 0.765 mmol) and 2- (trifluoromethyl)benzyl bromide (27.8 mg, 0.116 mmol) at room temperature for one day.

After addition of water under cooling with ice, the reaction mixture was extracted with 45 ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate → chloroform / methanol = 20/1 (v/v)) to give the title compound as a pale yellow oil, which was used for the next step.

REFERENCE SYNTHETIC EXAMPLE 80 rac{[(3R,4R)Methyl(4-oxo{[2-(trimethylsilyl)ethoxy]methyl}-4,7-dihydro-1H- pyrrolo[2,3-h][1,6]naphthyridinyl)piperidinyl]methyl}benzonitrile rac[(3R,4R)Methylpiperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one (25.0 mg, 0.0606 mmol) obtained in Reference Synthetic Example 36 in tetrahydrofuran (3 mL) was stirred with sodium hydride (55 wt% dispersion in mineral oil, 15.4 mg, 0.385 mmol) and 3-cyanobenzyl bromide (12.8 mg, 0.0653 mmol) at room temperature for one day. The reaction mixture was further stirred with sodium hydride (55 wt% dispersion in mineral oil, 20.8 mg, 0.520 mmol) and 3-cyanobenzyl bromide (11.6 mg, 0.0592 mmol) at room temperature for one day. After addition of water, the reaction mixture was extracted with chloroform twice, and the organic layer was concentrated under reduced pressure.

The residue was purified by silica gel column chromatography (ethyl acetate → chloroform / methanol = 10/1 (v/v)) to give the title compound as a pale yellow oil (32.4 mg, quantitative yield).

REFERENCE SYNTHETIC EXAMPLE 81 rac{[(3R,4R)Methyl(4-oxo{[2-(trimethylsilyl)ethoxy]methyl}-4,7-dihydro-1H- pyrrolo[2,3-h][1,6]naphthyridinyl)piperidinyl]methyl}benzonitrile The reactions in Reference Synthetic Example 77 were carried out in substantially the same manners except that 2-cyanobenzyl bromide was used instead of 3-(trifluoromethyl)benzyl bromide to give the title compound as a pale yellow oil (31.4 mg, yield 97%).

REFERENCE SYNTHETIC EXAMPLE 82 rac{[(3R,4R)Methyl(4-oxo{[2-(trimethylsilyl)ethoxy]methyl}-4,7-dihydro-1H- pyrrolo[2,3-h][1,6]naphthyridinyl)piperidinyl]methyl}benzonitrile The reactions in Reference Synthetic Example 77 were carried out in substantially the same manners except that 4-cyanobenzyl bromide was used instead of 3-(trifluoromethyl)benzyl bromide to give the title compound as a pale yellow oil (28.5 mg, yield 89%).

REFERENCE SYNTHETIC EXAMPLE 83 tert-Butyl rac-(3R,4R)methyl(4-oxo{[2-(trimethylsilyl)ethoxy]methyl}-4,7-dihydro- 1H-pyrrolo[2,3-h][1,6]naphthyridinyl)piperidincarboxylate rac[(3R,4R)Methylpiperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one (20 mg, 0.049 mmol) obtained in Reference Synthetic Example 36 in 1,4-dioxane (2 mL) was stirred with di-tert-butyl bicarbonate (40 mg, 0.18 mmol) and 1 M aqueous sodium hydroxide (200 µL. 0.200 mmol) at room temperature for 1 hour. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and 40 concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / methanol = 1/0 →10/1 (v/v)) to give the title compound as a colorless oil (21.1 mg, yield 85%).

REFERENCE SYNTHETIC EXAMPLE 84 rac[(3R,4R)(4-Fluorophenethyl)methylpiperidinyl]{[2- 45 (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one rac[(3R,4R)Methylpiperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one (20 mg, 0.049 mmol) obtained in Reference Synthetic Example 36 in a mixture of N,N-dimethylformamide (2 mL) and dichloromethane (1 mL) was stirred with 4-fluorophenethyl bromide (22 µL, 0.16 mmol) and N,N-diisopropylethylamine (20 µL, 0.11 mmol) at 50°C for 2 hours and then with sodium hydride (60 wt% dispersion in liquid paraffin,10 mg, 0.24 mmol) at 70°C for 5 hours. The reaction mixture was allowed to cool to room temperature and, after addition of saturated aqueous sodium chloride, extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ ethyl acetate = 1/1 → 0/1 (v/v)) to give a mixture (4.4 mg) containing the title compound.

The mixture was used for the next step without further purification.

REFERENCE SYNTHETIC EXAMPLE 85 rac[(3R,4R)cyclopentylmethylpiperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}- 1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one rac[(3R,4R)Methylpiperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one (32 mg, 0.078 mmol) obtained in Reference Synthetic Example 36 in a mixture of methanol (2 mL) and acetic acid (0.2 mL) was stirred with cyclopentanone (100 µL, 1.13 mmol) and 2-picoline borane (50 mg, 0.47 mmol) at room temperature for 1 hour. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting colorless oil (38 mg) containing the title compound was used for the next step without further purification.

REFERENCE SYNTHETIC EXAMPLE 86 1-{1-[4-(tert-Butyl)cyclohexanecarbonyl]methylpiperidinyl}{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one rac[(3R,4R)Methylpiperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one (20 mg, 0.049 mmol) obtained in Reference Synthetic Example 36 in chloroform (2 mL) was stirred with 4-(tert-butyl) cyclohexanecarboxylic acid (20 mg, 0.11 mmol), 1-(3-dimethylaminopropyl) ethylcarbodidimide hydrochloride (20 mg, 0.10 mmol) and N,N-diisopropylethylamine (50 µL, 0.29 mmol) at room temperature for 2 hours. After addition of 0.1 M aqueous sodium hydroxide, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed with 0.1 M hydrochloric acid, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate) to give two isomers of the title compound in a less polar fraction (Reference Synthetic Example 86a: colorless oil, 9.0 mg, yield 32%) and in more polar fraction (Reference Synthetic Example 86b: colorless oil, 9.3 mg, yield 33%).

REFERENCE SYNTHETIC EXAMPLE 87 4-Chloro{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinecarboxylic acid 4-Chloro{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine 40 carbaldehyde (486 mg, 1.56 mmol) obtained in Reference Synthetic Example 55 in acetic acid (10 mL) was mixed with sulfamic acid (227 mg, 2.34 mmol) and 2-methyl butene (486 µL, 4.58 mmol), and then sodium chlorite (254 mg, 2.81 mmol) in water (0.5 mL) was added dropwise. The resulting reaction mixture was stirred at room temperature for 2 hours, and after addition of water, adjusted to pH 7 with 1 M aqueous 45 sodium hydroxide and extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / methanol = 10/1 → 1/1 (v/v)) to give the title compound as a colorless solid (484 mg, yield 95%).

REFERENCE SYNTHETIC EXAMPLE 88 4-Chloro{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinecarboxamide 4-Chloro{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinecarboxylic acid (480 mg, 1.47 mmol) in thionyl chloride (3 mL) was stirred at room temperature for 2 hours. After addition of toluene, the reaction mixture was concentrated under reduced pressure, and after addition of toluene, concentrated under reduced pressure.

The residue was dissolved in dichloromethane (5 mL), and ammonia - methanol solution (7.0 M, 1.0 mL, 7.0 mmol) was added dropwise, and the resulting reaction mixture was stirred for 1 hour. After addition of saturated aqueous sodium chloride, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the title compound as a colorless solid (461 mg, yield 96%).

REFERENCE SYNTHETIC EXAMPLE 89 4-[(1-Benzylpiperidinyl)amino]{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- b]pyridinecarboxamide 4-Chloro{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine carboxamide (456 mg, 1.40 mmol) was stirred with 1-benzylaminopiperidine (900 mg, 4.73 mmol) and N,N-diisopropylethylamine (250 µL, 1.44 mmol) at 140°C for 3 hours.

The reaction mixture was allowed to cool to room temperature and, after addition of water, extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform → ethyl acetate / methanol = 1/0 → 5/1 (v/v)) to give the title compound as a colorless solid (542 mg, yield 81%).

REFERENCE SYNTHETIC EXAMPLE 90 1-(1-Benzylpiperidinyl){[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidine-2,4(3H,7H)-dione 4-[(1-Benzylpiperidinyl)amino]{[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[2,3-b]pyridinecarboxamide (484 mg, 1.01 mmol) in N,N-dimethylacetamide (5 mL) was stirred with 1,1’-carbonyldiimidazole (486 mg, 3.00 mmol) at 120°C for 3 hours.

The reaction mixture was allowed to cool to room temperature and, after addition of saturated aqueous sodium chloride, extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure.

The residue was purified by silica gel column chromatography (chloroform / methanol = /1 (v/v)) to give the title compound as a colorless solid (360 mg, yield 70%).

REFERENCE SYNTHETIC EXAMPLE 91 1-(Piperidinyl){[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[3’,2’:5,6]pyrido[4,3- d]pyrimidine-2,4(3H,7H)-dione hydrochloride 1-(1-Benzylpiperidinyl){[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidine-2,4(3H,7H)-dione (360 mg, 0.712 mmol) and 5% 40 palladium-carbon (100 mg) in a mixture of methanol and 10 wt % hydrogen chloride - methanol solution (0.5 mL) were stirred with at room temperature for 2 hours under a hydrogen atmosphere, then at 40°C for 5 hours and at room temperature for one day.

The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give the title compound as a colorless solid (324 mg, quantitative yield). 45 REFERENCE SYNTHETIC EXAMPLE 92 4-{[4-(2,4-Dioxo{[2-(trimethylsilyl)ethoxy]methyl}-2,3,4,7-tetrahydro-1H- pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidinyl)piperidinyl]methyl}benzonitrile 1-(Piperidinyl){[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidine-2,4(3H,7H)-dione hydrochloride (50 mg, 0.111 mmol) and 4-cyanobenzaldehyde (29 mg, 0.22 mmol) in a mixture of methanol (2 ml) and acetic acid (0.2 mL) were stirred with 2-picoline borane (50 mg, 0.47 mmol) at room temperature for 2 days. After addition of 1 M aqueous sodium hydroxide, the reaction mixture was extracted with a mixture of ethyl acetate and 2-propanol, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform / methanol = 10/1 (v/v)) to give the title compound as a colorless solid (23.4 mg, yield 40%).

REFERENCE SYNTHETIC EXAMPLE 93 1-{1-[(5-Chlorothiophenyl)methyl]piperidinyl}{[2-(trimethylsilyl)ethoxy]methyl}- 1H-pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidine-2,4(3H,7H)-dione The reactions in Reference Synthetic Example 92 were carried out in substantially the same manners except that 5-chlorothiophenecarbaldehyde was used instead of 4-cyanobenzaldehyde to give the title compound as a colorless solid (21.1 mg, yield 58%).

REFERENCE SYNTHETIC EXAMPLE 94 1-{1-[4-(Trifluoromethyl)benzyl]piperidinyl}{[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidine-2,4(3H,7H)-dione The reactions in Reference Synthetic Example 92 were carried out in substantially the same manners except that 4-(trifluoromethyl)benzaldehyde was used instead of 4-cyanobenzaldehyde to give the title compound as a colorless amorphous (28.1 mg, yield 44%).

REFERENCE SYNTHETIC EXAMPLE 95 1-Cyclohexyl{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[3’,2’:5,6]pyrido[4,3- d]pyrimidine-2,4(3H,7H)-dione 4-(Cyclohexylamino){[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine- -carboxamide (26 mg, 0.067 mmol) obtained in Reference Synthetic Example 30 in N,N-dimethylacetamide (1 mL) was stirred with 1,1’-carbonyldiimidazole (22 mg, 0.14 mmol) at 170°C for 2 hours under microwave irradiation. The reaction mixture was allowed to cool to room temperature and, after addition of water, extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1/1 (v/v)) to give the title compound as a colorless solid (13.7 mg, yield 49%).

REFERENCE SYNTHETIC EXAMPLE 96 1-(4-Chloro{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinyl)ethanone Methylmagnesium bromide - diethyl ether solution (3.0 M, 10 mL, 30 mmol) was added dropwise to 4-chloro{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- 40 b]pyridinecarbaldehyde (4.89 g, 15.7 mmol) obtained in Reference Synthetic Example 55 in tetrahydrofuran (50 mL) under cooling with ice, and the reaction mixture was stirred for 2 hours. After dropwise addition of water and addition of saturated aqueous ammonium chloride, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under 45 reduced pressure. The residue was dissolved in 1,2-dimethoxyethane (25 mL) and vigorously stirred with manganese dioxide (9.0 g, 0.10 mol) at 80°C for 4 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure.

The residue was dissolved in 1,2-dimethoxyethane (25 mL) and vigorously stirred with manganese dioxide (9.0 g, 0.10 mol) at 80°C for 4 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 10/1 (v/v)) to give the title compound as an orange oil (3.09 g, yield 61%). (alternative to Reference Synthetic Example 33) REFERENCE SYNTHETIC EXAMPLE 97 1-(4-[(1-Benzylpiperidinyl)amino]{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- b]pyridinyl)ethanone 1-(4-Chloro{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin yl)ethanone (400 mg, 1.23 mmol) and 1-benzylpiperidinamine (1.70 mL, 8.93 mmol) was stirred with N,N-diisopropylethylamine (251 µL. 1.47 mmol) at 140°C for one day.

The reaction mixture was purified by silica gel column chromatography (hexane / ethyl acetate = 1/1 (v/v)) to give the title compound (343 mg, yield 58%).

REFERENCE SYNTHETIC EXAMPLE 98 1-(1-Benzylpiperidinyl){[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- h][1,6]naphthyridin-4(7H)-one 1-{4-[(1-Benzylpiperidinyl)amino]{[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[2,3-b]pyridinyl}ethanone (343 mg, 0.720 mmol) in N,N-dimethylformamide dimethyl acetal (2 mL) was stirred at 170°C for 6 hours under microwave irradiation.

The reaction mixture was allowed to cool to room temperature and concentrated under reduced pressure, and the residue was dissolved in tetrahydrofuran (5 mL) and stirred with 1 M hydrochloric acid (3 mL) at 80°C for 1 hour. After addition of saturated aqueous sodium hydrogen carbonate, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform / methanol = 9/1 (v/v)) to give the title compound (299 mg, yield 85%).

REFERENCE SYNTHETIC EXAMPLE 99 1-(Piperidinyl){[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-h][1,6]naphthyridin- 4(7H)-one 1-(1-Benzylpiperidinyl){[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- h][1,6]naphthyridin-4(7H)-one (341 mg, 0.697 mmol) in methanol was stirred with 5% palladium-carbon (500 mg) for one day under a hydrogen atmosphere. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Hi Flash column amino type manufactured by Yamazen Corporation: chloroform / methanol = 9/1/ (v/v)) to give the title compound (189 mg, yield 68%).

REFERENCE SYNTHETIC EXAMPLE 100 1-{1-[(5-Chlorothiophenyl)methyl]piperidinyl}{[2-(trimethylsilyl)ethoxy]methyl}- 40 1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one 1-(Piperidinyl){[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- h][1,6]naphthyridin-4(7H)-one (20 mg, 0.050 mmol) in methanol was stirred with 5- chlorothiophencarbaldehyde (6.3 µL, 0.06 mmol), 2-picoline borane (6.4 mg, 0.06 mmol) and acetic acid (100 µL) for one day. The reaction mixture was concentrated 45 under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform / methanol = 10/1 (v/v)) to give the title compound as a colorless oil (20 mg, yield 75%).

REFERENCE SYNTHETIC EXAMPLE 101 1-{1-[4-(Trifluoromethyl)benzyl]piperidinyl}{[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one 1-(Piperidinyl){[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- h][1,6]naphthyridin-4(7H)-one (20 mg, 0.050 mmol) obtained in Reference Synthetic Example 99 in dichloromethane was stirred with 4-(trifluoromethyl)benzyl bromide (14.3 mg, 0.0600 mmol) and triethylamine (10.5 µL, 0.0750 mmol) for one day. After addition of water, the reaction mixture was extracted with chloroform, and the organic layer as dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform / methanol = 9/1 (v/v)) to give the title compound (20 mg, yield 72%).

REFERENCE SYNTHETIC EXAMPLE 102 4-{[4-(4-Oxo{[2-(trimethylsilyl)ethoxy]methyl}-4,7-dihydro-1H-pyrrolo[2,3- h][1,6]naphthyridinyl)piperidinyl]methyl}benzonitrile The reactions in Reference Synthetic Example 101 were carried out in substantially the same manners except that 4-cyanobenzyl bromide was used instead of 4-(trifluoromethyl)benzyl bromide to give the title compound (29.7 mg, yield 77%).

REFERENCE SYNTHETIC EXAMPLE 103 3-Fluoro{[4-(4-oxo{[2-(trimethylsilyl)ethoxy]methyl}-4,7-dihydro-1H-pyrrolo[2,3- h][1,6]naphthyridinyl)piperidinyl]methyl}benzonitrile The reactions in Reference Synthetic Example 101 were carried out in substantially the same manners except that 4-(bromomethyl)fluorobenzonitrile was used instead of 4-(trifluoromethyl)benzyl bromide to give the title compound as a yellow oil (17.6 mg, yield 66%).

REFERENCE SYNTHETIC EXAMPLE 104 4-[(1-Benzylpiperidinyl)amino]-1H-pyrrolo[2,3-b]pyridinecarbaldehyde 4-Chloro-1H-pyrrolo[2,3-b]pyridinecarbaldehyde (600 mg, 3.32 mmol) obtained in Reference Synthetic Example 7 and 1-benzylpiperidinamine (2.53 g, 13.3 mmol) in ethylene glycol (300 µL) were stirred at 180°C for 2 hours under microwave irradiation. The reaction mixture was allowed to cool to room temperature and, after addition of water, extracted with chloroform, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in 1,4-dioxane (5 mL) and stirred with 4 M hydrogen chloride - 1,4-dioxane solution (5 mL) and water (2 mL) at room temperature for one day.

The reaction mixture was concentrated under reduced pressure, adjusted to pH 9 or above with 1M aqueous sodium hydroxide and extracted with chloroform and water, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Hi Flash column amino type manufactured by Yamazen Corporation: hexane / ethyl acetate = 1/1 (v/v)) to give the title compound ( 672 mg, yield 60%). 40 REFERENCE SYNTHETIC EXAMPLE 105 4-[(1-Benzylpiperidinyl)amino]{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- b]pyridinecarbaldehyde 4-[(1-Benzylpiperidinyl)amino]-1H-pyrrolo[2,3-b]pyridinecarbaldehyde (672 mg, 2.01 mmol) in N,N-dimethylformamide (5 mL) was mixed with sodium hydride (55 45 wt% dispersion in mineral oil, 436 mg, 10.0 mmol) under cooling with ice, and the reaction mixture was stirred for 30 minutes. The reaction mixture was stirred with [2- (chloromethoxyl)ethyl]trimethylsilane (885 µL, 5.00 mmol) at room temperature for one day. After addition of water, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1/1 (v/v)) to give the title compound (392 mg, yield 42%).

REFERENCE SYNTHETIC EXAMPLE 106 {4-[(1-Benzylpiperidinyl)amino]{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- b]pyridinyl}methanol 4-[(1-Benzylpiperidinyl)amino]{[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[2,3-b]pyridinecarbaldehyde (289 mg, 0.620 mmol) in methanol was stirred with sodium borohydride (35.3 mg, 0.93 mmol) at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure and, after addition of water, extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ ethyl acetate = 1/1(v/v)) to give the title compound (258 mg, yield 89%).

REFERENCE SYNTHETIC EXAMPLE 107 -(Aminomethyl)-N-(1-benzylpiperidinyl) {[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[2,3-b]pyridinamine {4-[(1-Benzylpiperidinyl)amino]{[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[2,3-b]pyridinyl}methanol (212 mg, 0.454 mmol), phthalimide (134 mg, 0.909 mmol) and triphenylphosphine (238 mg, 0.909 mmol) in tetrahydrofuran was stirred at room temperature for 30 minutes and with diisopropyl azodicarboxylate (184 mg, 0.909 mmol) for one day. The reaction mixture was concentrated under reduced pressure and, after addition of water, extracted with ethyl acetate. The residue was purified by silica gel column chromatography (hexane/ ethyl acetate = 1/1/ (v/v)) to remove triphenylphosphine oxide. The residue was dissolved in ethanol (10 mL) and stirred with hydrazine monohydrate (1.00 mL, 11.6 mmol) at 80°C for 1 hour. The reaction mixture was concentrated under reduced pressure and, after addition of water, extracted with chloroform, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1/1 (v/v)) to give the title compound (51.1 mg, yield 24%).

REFERENCE SYNTHETIC EXAMPLE 108 1-(1-Benzylpiperidinyl){[2-(trimethylsilyl)ethoxy]methyl}-3,4-dihydro-1H- pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidin-2(7H)-one 5-(Aminomethyl)-N-(1-benzylpiperidinyl) {[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[2,3-b]pyridinamine (38 mg, 0.081 mmol) in dichloromethane was stirred with 1,1’-carbonyldiimidazole (20.0 mg, 0.123 mmol) at 80°C for 1 hour. The reaction mixture was concentrated under reduced pressure and, after addition of water, extracted with ethyl acetate, and the organic layer was dried over anhydrous 40 magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform / methanol =10/1 (v/v)) to give the title compound (30.9 mg, yield 77%).

REFERENCE SYNTHETIC EXAMPLE 109 1-(Piperidinyl){[2-(trimethylsilyl)ethoxy]methyl}-3,4-dihydro-1H- 45 pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidin-2(7H)-one 1-(1-Benzylpiperidinyl){[2-(trimethylsilyl)ethoxy]methyl}-3,4-dihydro-1H- pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidin-2(7H)-one (61 mg, 0.12 mmol) in ethanol was stirred with 5% palladium-carbon (60 mg) for one day under a hydrogen atmosphere.

The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give the title compound (48 mg, yield 100%).

REFERENCE SYNTHETIC EXAMPLE 110 1-[1-(Benzylsulfonyl)piperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}-3,4-dihydro-1H- pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidin-2(7H)-one 1-(Piperidinyl){[2-(trimethylsilyl)ethoxy]methyl}-3,4-dihydro-1H- pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidin-2(7H)-one (18.5 mg, 0.0460 mmol) in dichloromethane was mixed with phenylmethanesulfonyl chloride (17.5 mg, 0.092 mmol) and triethylamine (12.8 µL, 0.0920 mmol) for 1 hour under cooling with ice.

After addition of water, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform / methanol = 9/1 (v/v)) to give the title compound as a pale yellow solid (18.4 mg, yield 72%).

REFERENCE SYNTHETIC EXAMPLE 111 1-[1-(Pyridinylmethyl)piperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}-3,4-dihydro- 1H-pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidin-2(7H)-one The reactions in Reference Synthetic Example 110 were carried out in substantially the same manners except that 3-picolyl bromide was used instead of phenylmethanesulfonyl chloride to give the title compound (14 mg, yield 46%).

REFERENCE SYNTHETIC EXAMPLE 112 4-{[4-(2-Oxo{[2-(trimethylsilyl)ethoxy]methyl}-2,3,4,7-tetrahydro-1H- pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidinyl)piperidinyl]methyl}benzonitrile The reactions in Reference Synthetic Example 110 were carried out in substantially the same manners except that 4-cyanobenzyl bromide was used instead of phenylmethanesulfonyl chloride to give the title compound (20.6 mg, yield 54%).

REFERENCE SYNTHETIC EXAMPLE 113 1-{1-[4-(Trifluoromethyl)benzyl]piperidinyl}{[2-(trimethylsilyl)ethoxy]methyl}-3,4- dihydro-1H-pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidin-2(7H)-one The reactions in Reference Synthetic Example 110 were carried out in substantially the same manners except that 4-(trifluoromethyl)benzyl bromide was used instead of phenylmethanesulfonyl chloride to give the title compound (18.9 mg, yield 46%).

REFERENCE SYNTHETIC EXAMPLE 114 4-(2-Oxo{[2-(trimethylsilyl)ethoxy]methyl}-2,3,4,7-tetrahydro-1H- pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidinyl)-N-(1,3,4-thiadiazolyl)piperidine carboxamide 1-(Piperidinyl){[2-(trimethylsilyl)ethoxy]methyl}-3,4-dihydro-1H- pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidin-2(7H)-one (16.3 mg, 0.0407 mmol) obtained in 40 Reference Synthetic Example 109 and phenyl 1,3,4-thiadiazolylcarbamate (10.8 mg, 0.0488 mol) obtained in Reference Synthetic Example 72 in tetrahydrofuran was stirred with triethylamine (8.1µL, 0.061 mmol) at 60°C for 2 hours. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue 45 was purified by silica gel column chromatography (chloroform / methanol = 9/1 (v/v)) to give the title compound as a colorless solid (20 mg, yield 93%).

REFERENCE SYNTHETIC EXAMPLE 115 1-[1-(3,3,3-Trifluoropropanoyl)piperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}-3,4- dihydro-1H-pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidin-2(7H)-one 1-(Piperidinyl){[2-(trimethylsilyl)ethoxy]methyl}-3,4-dihydro-1H- pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidin-2(7H)-one (25 mg, 0.062 mmol) obtained in Reference Synthetic Example 109 in N,N-dimethylformamide was stirred with 3,3,3- trifluoropropionic acid (8.7 mg, 0.068 mmol), O-(7-azabenzotriazolyl)-N,N,N’,N’- tetramethyluronium hexafluorophosphate (28.1 mg, 0.0740 mmol) and N,N- diisopropylethylamine (21.2 µL, 0.124 mmol) at room temperature for 2 hours. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform / methanol = 10/1 (v/v)) to give the title compound as a yellow oil (15.5 mg, yield 49%).

REFERENCE SYNTHETIC EXAMPLE 116 1-[1-(Thiazolylmethyl)piperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}-3,4-dihydro- 1H-pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidin-2(7H)-one 1-(Piperidinyl){[2-(trimethylsilyl)ethoxy]methyl}-3,4-dihydro-1H- pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidin-2(7H)-one (20 mg, 0.050 mmol) obtained in Reference Synthetic Example 109 in methanol was stirred with thiazolcarbaldehyde (6.6 µL, 0.075 mmol), 2-picoline borane (8.0 mg, 0.075 mmol) and acetic acid (100 µL) for one day. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform / methanol = 10/1 (v/v)) to give the title compound (12 mg, yield 48%).

REFERENCE SYNTHETIC EXAMPLE 117 rac{[(3R,4R)Benzylmethylpiperidinyl]amino}-1H-pyrrolo[2,3-b]pyridine carbaldehyde The reactions in Reference Synthetic Example 104 were carried out in substantially the same manners except that rac-(3R,4R)benzylmethylpiperidin amine obtained in Reference Synthetic Example 3 was used instead of 1- benzylpiperidinamine to give the title compound as a brown oil (282 mg, yield 30%). (alternative to Reference Synthetic Example 38) REFERENCE SYNTHETIC EXAMPLE 118 rac{[(3R,4R)Benzylmethylpiperidinyl]amino}{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinecarbaldehyde The reactions in Reference Synthetic Example 105 were carried out in substantially the same manners except that rac{[(3R,4R)benzylmethylpiperidin- 3-yl]amino}-1H-pyrrolo[2,3-b]pyridinecarbaldehyde was used instead of 4-[(1- benzylpiperidinyl)amino]-1H-pyrrolo[2,3-b]pyridinecarbaldehyde to give the title compound (231 mg, yield 60%). (alternative to Reference Synthetic Example 39) REFERENCE SYNTHETIC EXAMPLE 119 rac-(4-{[(3R,4R)Benzylmethylpiperidinyl]amino}{[2- 40 (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinyl)methanol The reactions in Reference Synthetic Example 106 were carried out in substantially the same manners except that rac{[(3R,4R)benzylmethylpiperidin- 3-yl]amino}{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinecarbaldehyde was used instead of 4-[(1-benzylpiperidinyl)amino]{[2- 45 (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinecarbaldehyde to give the title compound as a yellow oil (105 mg, yield 84%). (alternative to Reference Synthetic Example 40) REFERENCE SYNTHETIC EXAMPLE 120 rac(Aminomethyl)-N-[(3R,4R)benzylmethylpiperidinyl]{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinamine The reactions in Reference Synthetic Example 107 were carried out in substantially the same manners except that rac-(4-{[(3R,4R)benzylmethylpiperidin- 3-yl]amino}{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinyl)methanol was used instead of {4-[(1-benzylpiperidinyl)amino]{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinyl}methanol to give the title compound (20.8 mg, yield 21%).

REFERENCE SYNTHETIC EXAMPLE 121 rac[(3R,4R)benzylmethylpiperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}-3,4- dihydro-1H-pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidin-2(7H)-one The reactions in Reference Synthetic Example 108 were carried out in substantially the same manners except that rac(aminomethyl)-N-[(3R,4R)benzyl methylpiperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine amine was used instead of 5-(aminomethyl)-N-(1-benzylpiperidinyl) {[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridineamine to give the title compound (22 mg, yield 100%).

REFERENCE SYNTHETIC EXAMPLE 122 (transAminocyclohexyl)methanol transAminocyclohexanecarboxylic acid (314 mg, 2.19 mmol) was gradually added to sodium bis(2-methoxyethoxy)aluminum hydride - toluene solution (65 wt%, 3.0 mL) in toluene (3mL) at 75°C, and the reaction mixture was stirred for 7 hours. The reaction mixture was allowed to cool to room temperature and stirred with 1 M aqueous sodium hydroxide (20 mL) at 80°C for 10 minutes. The reaction mixture was allowed to cool to room temperature and partitioned between water and toluene, and the aqueous layer was extracted with chloroform three times. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the title compound as a colorless solid (170 mg, yield 60%).

REFERENCE SYNTHETIC EXAMPLE 123 1-(4-{[trans(Hydroxymethyl)cyclohexyl]amino}{[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[2,3-b]pyridinyl)ethanone (transAminocyclohexyl)methanol (170 mg, 1.32 mmol) and 1-(4-chloro{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinyl)ethanone (120 mg, 0.369 mmol) obtained in Reference Synthetic Example 96 in N,N-dimethylacetamide (1 mL) were stirred with N,N-diisopropylethylamine (128 µL, 0.735 mmol) at 140°C for 7 hours.

The reaction mixture was allowed to cool to room temperature and, after addition of saturated aqueous sodium chloride, extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica 40 gel column chromatography (ethyl acetate) to give the title compound as a pale yellow oil (118 mg, yield 77%).

REFERENCE SYNTHETIC EXAMPLE 124 1-[trans(Hydroxymethyl)cyclohexyl]{[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one 45 The reactions in Reference Synthetic Example 98 were carried out in substantially the same manners except that 1-(4-{[trans (Hydroxymethyl)cyclohexyl]amino}{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- b]pyridinyl)ethanone was used instead of 1-{4-[(1-benzylpiperidinyl)amino]{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinyl}ethanone to give the title compound as a pale yellow solid (35 mg, yield 29%).

REFERENCE SYNTHETIC EXAMPLE 125 tert-Butyl (transmethoxycyclohexyl)carbamate tert-Butyl (transhydroxycyclohexyl)carbamate (1.0 g, 4.6 mmol) in tetrahydrofuran (20 mL) was stirred with sodium hydride (55 wt% dispersion in mineral oil, 24 mg, 6.4 mmol) and 15-crown-5 ether (965 µL) for 30 minutes under cooling with ice and then with iodomethane (289 µL) at room temperature for 1 hour. Methanol (2 mL) was added to the reaction mixture, and the precipitated solid was removed by filtration. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 8/1 (v/v)) to give the title compound (708 mg, yield 67%).

REFERENCE SYNTHETIC EXAMPLE 126 transMethoxycyclohexanamine hydrochloride tert-Butyl (transmethoxycyclohexyl)carbamate in ethanol (5 mL) was stirred with acetyl chloride (1.5 mL) for one day under cooling with ice, and the solvent was concentrated under reduced pressure to give the title compound (475 mg, yield 95%).

REFERENCE SYNTHETIC EXAMPLE 127 1-(4-[(transMethoxycyclohexyl)amino]{[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[2,3-b]pyridinyl)ethanone 1-(4-Chloro{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin yl)ethanone (228 mg, 0.170 mmol) obtained in Reference Synthetic Example 96 in ethylene glycol (1 mL) was stirred with transmethoxycyclohexanamine hydrochloride and N,N-diisopropylethylamine at 180°C for 1 hour under microwave irradiation. After addition of saturated aqueous sodium hydrogen carbonate, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1/9 (v/v)) to give the title compound as a yellow oil (179 mg, yield 61%).

REFERENCE SYNTHETIC EXAMPLE 128 1-(transMethoxycyclohexyl){[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- h][1,6]naphthyridin-4(7H)-one 1-(4-[(transMethoxycyclohexyl)amino]{[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[2,3-b]pyridinyl)ethanone (179 mg, 0.428 mmol) in N,N-dimethylformamide dimethyl acetal (3 mL) was stirred at 170°C for 6 hours under microwave irradiation.

The reaction mixture was allowed to cool to room temperature and concentrated under reduced pressure, and the resulting residue was dissolved in tetrahydrofuran (3 mL) and stirred with 1 M hydrochloric acid (3 mL) at 80°C for 1 hour. The reaction mixture was allowed to cool to room temperature and, after addition of saturated aqueous 40 sodium hydrogen carbonate, extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform / methanol = 9/1 (v/v)) to give the title compound (141 mg, yield 77%).

REFERENCE SYNTHETIC EXAMPLES 129 TO 134 45 The reactions in Reference Synthetic Example 101 were carried out in substantially the same manners except that 2-(bromomethyl)(trifluoromethyl)furan, 2- (bromomethyl)nitrofuran, ethyl 5-(chloromethyl)furancarboxylate, 4-(chloromethyl)- 1,2-difluorobenzene, 1,2-dichloro(chloromethyl)benzene or 5-(chloromethyl) (trifluoromethyl)pyridine was used instead of 4-(trifluoromethyI)benzyl bromide to give the compounds of Reference Examples 129 to 134. The names and yields of the compounds synthesized are shown in Table 5.

TABLE 5 Rf Compound Name Yield 1-(1-{[5-(trifluoromethyl)furanyl]methyl}pi peridinyl){[2-(trimethylsilyl)ethoxy]met 129 74% hyl}-1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)- 1-{1-[(5-nitrofuranyl)methyl]piperidinyl 130 }{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrr 84% olo[2,3-h][1,6]naphthyridin-4(7H)-one Ethyl -{[4-(4-oxo{[2-(trimethylsilyl)ethoxy]meth 131 yl}-4,7-dihydro-1H-pyrrolo[2,3-h][1,6]naphthyr 74% idinyl)piperidinyl]methyl}furancarbox ylate 1-[1-(3,4-difluorobenzyl)piperidinyl]{[2 132 -(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3 82% -h][1,6]naphthyridin-4(7H)-one 1-[1-(3,4-dichlorobenzyl)piperidinyl]{[2 133 -(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3 95% -h][1,6]naphthyridin-4(7H)-one 1-(1-{[6-(trifluoromethyl)pyridinyl]methyl} piperidinyl){[2-(trimethylsilyl)ethoxy]m 134 79% ethyl}-1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H )-one REFERENCE SYNTHETIC EXAMPLES 135 TO 143 The reactions in Reference Synthetic Example 100 were carried out in substantially the same manners except that 2-chlorothiazolecarbaldehyde, 4-fluoro (trifluoromethyl)benzaldehyde, 5-nitrothiophenecarbaldehyde, 5-bromofuran carbaldehyde, 5-bromothiophenecarbaldehyde, 4-bromothiophenecarbaldehyde, 2-bromothiazolecarbaldehyde, 2,2-difluorobenzo[d][1,3]dioxolecarbaldehyde or 1H-indolecarbaldehyde was used instead of 5-chlorothiophenecarbaldehyde to give the compounds of Reference Examples 135 to 143. The names and yields of the compounds synthesized are shown in Table 6.

TABLE 6 Rf Compound Name Yield 1-{1-[(2-chlorothiazolyl)methyl]piperidin-4 135 -yl}{[2-(trimethylsilyl)ethoxy]methyl}-1H-p 82% yrrolo[2,3-h][1,6]naphthyridin-4(7H)-one 1-{1-[4-fluoro(trifluoromethyl)benzyl]piper 136 idinyl}{[2-(trimethylsilyl)ethoxy]methyl 86% }-1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one 1-{1-[(5-nitrothiophenyl)methyl]piperidin-4 137 -yl}{[2-(trimethylsilyl)ethoxy]methyl}-1H-p 86% yrrolo[2,3-h][1,6]naphthyridin-4(7H)-one 1-{1-[(5-bromofuranyl)methyl]piperidinyl 138 }{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrr 80% olo[2,3-h][1,6]naphthyridin-4(7H)-one 1-{1-[(5-bromothiophenyl)methyl]piperidin-4 139 -yl}{[2-(trimethylsilyl)ethoxy]methyl}-1H-p 78% yrrolo[2,3-h][1,6]naphthyridin-4(7H)-one 1-{1-[(4-bromothiophenyl)methyl]piperidin-4 140 -yl}{[2-(trimethylsilyl)ethoxy]methyl}-1H-p 65% yrrolo[2,3-h][1,6]naphthyridin-4(7H)-one 1-{1-[(2-bromothiazolyl)methyl]piperidin 141 yl}{[2-(trimethylsilyl)ethoxy]methyl}-1H-py 80% rrolo[2,3-h][1,6]naphthyridin-4(7H)-one 1-{1-[(2,2-difluorobenzo[d][1,3]dioxolyl)me thyl]piperidinyl}{[2-(trimethylsilyl)eth 142 94% oxy]methyl}-1H-pyrrolo[2,3-h][1,6]naphthyridin -4(7H)-one 1-{1-[(1H-indolyl)methyl]piperidinyl} 143 {[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[ 81% 2,3-h][1,6]naphthyridin-4(7H)-one REFERENCE SYNTHETIC EXAMPLE 144 1-[1-(5-Chlorothiophenecarbonyl)piperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}- 1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one 1-(Piperidinyl){[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- h][1,6]naphthyridin-4(7H)-one (20 mg, 0.050 mmol) obtained in Reference Synthetic Example 99 in N,N-dimethylformamide (2 mL) was stirred with 5-chlorothiophene carboxylic acid (13.4 mg, 0.0825 mmol), N,N-diisopropylethylamine (25.5 µL, 0.150 mmol) and O-(7-azabenzotriazolyl)-N,N,N’,N’-tetramethyluronium hexafluorophosphate (34.2 mg, 0.0899 mmol) for one day. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform / methanol = 9/1 (v/v)) to give the title compound (40.0 mg, quantitative yield).

REFERENCE SYNTHETIC EXAMPLES 145 TO 150 The reactions in Reference Synthetic Example 92 were carried out in substantially the same manners except that tert-butyl (2-oxoethyl)carbamate, 5- bromothiophenecarbaldehyde, 2-(tetrahydro-2H-thiopyranyl)acetaldehyde, cyclopropanecarbaldehyde, 2-methylbutanal or 2-(tetrahydro-2H-pyran yl)acetaldehyde was used instead of 4-cyanobenzaldehyde to give the compounds of Reference Synthetic Examples 145 to 150. The names, morphologies and yields of the compounds synthesized are shown in Table 7.

TABLE 7 Rf Compound Name Morphology Yield tert-butyl {2-[4-(2,4-dioxo{[2-(trimethylsilyl)et Colorless 145 hoxy]methyl}-2,3,4,7-tetrahydro-1H-pyrrol 89% solid o[3',2':5,6]pyrido[4,3-d]pyrimidinyl)p iperidinyl]ethyl}carbamate 1-{1-[(5-bromothiophenyl)methyl]piperi dinyl}{[2-(trimethylsilyl)ethoxy]me Colorless 146 70% thyl}-1H-pyrrolo[3',2':5,6]pyrido[4,3-d]p solid yrimidine-2,4(3H,7H)-dione 1-{1-[2-(tetrahydro-2H-thiopyranyl)eth yl]piperidinyl}{[2-(trimethylsilyl) Yellow 147 36% ethoxy]methyl}-1H-pyrrolo[3',2':5,6]pyrid oil o[4,3-d]pyrimidine-2,4(3H,7H)-dione 1-[1-(cyclopropylmethyl)piperidinyl]-7 -{[2-(trimethylsilyl)ethoxy]methyl}-1H-py Colorless 148 51% rrolo[3',2':5,6]pyrido[4,3-d]pyrimidine-2 solid ,4(3H,7H)-dione 1-[1-(2-methylbutyl)piperidinyl]{[2 -(trimethylsilyl)ethoxy]methyl}-1H-pyrrol Colorless 149 56% o[3',2':5,6]pyrido[4,3-d]pyrimidine-2,4(3 solid H,7H)-dione 1-{1-[2-(tetrahydro-2H-pyranyl)ethyl]p iperidinyl}{[2-(trimethylsilyl)etho Colorless 150 80% xy]methyl}-1H-pyrrolo[3',2':5,6]pyrido[4, solid 3-d]pyrimidine-2,4(3H,7H)-dione REFERENCE SYNTHETIC EXAMPLE 151 2-[4-(2,4-Dioxo{[2-(trimethylsilyl)ethoxy]methyl}-2,3,4,7-tetrahydro-1H- pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidinyl)piperidinyl]acetonitrile 1-(Piperidinyl){[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidine-2,4(3H,7H)-dione hydrochloride (40.0 mg, 0.0885 mmol) obtained in Reference Synthetic Example 91 in acetonitrile (1 mL) was mixed with 2-chloroacetonitrile （8.2 µL, 0.133 mmol ） and N,N-diisopropylethylamine (31.0 µL, 0.177 mmol) and stirred at 60°C for 26 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform → methanol / chloroform = 8/92 (v/v)) to give the title compound as a colorless solid (31.2 mg, yield 78%).

REFERENCE SYNTHETIC EXAMPLES 152 TO 156 The reactions in Reference Synthetic Example 151 were carried out in substantially the same manners except that 2,2,2-trifluoroethyl trifluoromethanesulfonate, 5-bromopentanenitrile, 6-bromo-1,1,1-trifluorohexane, 4- bromobutanenitrile or 2-(bromomethyl)tetrahydrofuran was used instead of 2- chloroacetonitrile to give the compounds of Reference Synthetic Examples 152 to 156.

The names, morphologies and yields of the compounds synthesized are shown in Table 8.

TABLE 8 Rf Compound Name Morphology Yield 1-[1-(2,2,2-trifluoroethyl)piperidi nyl]{[2-(trimethylsilyl)ethox Colorless 152 y]methyl}-1H-pyrrolo[3',2':5,6]pyri 81% solid do[4,3-d]pyrimidine-2,4(3H,7H)-dion -[4-(2,4-dioxo{[2-(trimethylsil yl)ethoxy]methyl}-2,3,4,7-tetrahydr Colorless 153 o-1H-pyrrolo[3',2':5,6]pyrido[4,3-d 78% solid ]pyrimidinyl)piperidinyl]pent anenitrile 1-[1-(6,6,6-trifluorohexyl)piperidi nyl]{[2-(trimethylsilyl)ethox Pale yellow 154 y]methyl}-1H-pyrrolo[3',2':5,6]pyri 83% solid do[4,3-d]pyrimidine-2,4(3H,7H)-dion 4-[4-(2,4-dioxo{[2-(trimethylsil yl)ethoxy]methyl}-2,3,4,7-tetrahydr Colorless 155 76% o-1H-pyrrolo[3',2':5,6]pyrido[4,3-d solid ]pyrimidinyl)piperidinyl]buta nenitrile 1-{1-[(tetrahydrofuranyl)methyl] piperidinyl}{[2-(trimethylsil Pale orange 156 yl)ethoxy]methyl}-1H-pyrrolo[3',2': 65% solid ,6]pyrido[4,3-d]pyrimidine-2,4(3H, 7H)-dione REFERENCE SYNTHETIC EXAMPLE 157 3-[4-(2,4-Dioxo{[2-(trimethylsilyl)ethoxy]methyl}-2,3,4,7-tetrahydro-1H- pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidinyl)piperidinyl]propanenitrile 1-(Piperidinyl){[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidine-2,4(3H,7H)-dione hydrochloride (40.0 mg, 0.0885 mmol) obtained in Reference Synthetic Example 91 in ethanol (1 mL) was refluxed with acrylonitrile （11.5 µL, 0.176 mmol ）and N,N-diisopropylethylamine (18.9 µL, 0.110 mmol) for 8.5 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform → methanol / chloroform = 6/94 (v/v)) to give the title compound as a colorless solid (27.3 mg, yield 66%).

REFERENCE SYNTHETIC EXAMPLE 158 4-Aminoadamantanol Concentrated sulfuric acid (35 mL) was mixed with concentrated nitric acid (4.5 mL) and 2-adamantylamine (5.10 g, 4.57 mmol) under cooling with ice, and the reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was added to ice water and adjusted to pH 10 with 7.5 M aqueous sodium hydroxide. After addition of water, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give the title compound as a yellow solid (2.79 g, yield 61%).

REFERENCE SYNTHETIC EXAMPLE 159 159a: Benzyl [(1R,2s,3S,5s,7s)hydroxyadamantanyl]carbamate 159b: Benzyl [(1R,2r,3S,5s,7s)hydroxyadamantanyl]carbamate 4-Aminoadamantanol (2.57 g, 15.4 mmol) in tetrahydrofuran (25 mL) was mixed with benzyl chloroformate (2.30 mL, 16.1 mmol) and 1 M aqueous sodium hydroxide (16.0 mL, 16.0 mmol) under cooling with ice and then stirred at room temperature for one day. After addition of 10% aqueous potassium hydrogen sulfate, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1/2 (v/v)) to give benzyl [(1R,2s,3S,5s,7s) hydroxyadamantanyl]carbamate (Reference Synthetic Example 159a; yellow oil, 1.72 g, yield 37%) in a more polar fraction and benzyl [(1R,2r,3S,5s,7s) hydroxyadamantanyl]carbamate (Reference Synthetic Example 159b; yellow oil, 2.24 g, yield 48%) in a less polar fraction.

REFERENCE SYNTHETIC EXAMPLE 160 (1s,3R,4s,5S,7s)Aminoadamantanol Benzyl [(1R,2s,3S,5s,7s)hydroxyadamantanyl]carbamate (318 mg, 1.05 mmol) obtained in Reference Synthetic Example 159a and 5% palladium-carbon (63 mg) in methanol (2 mL) were stirred at room temperature for one day under a hydrogen atmosphere. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give the title compound as a colorless solid (144 mg, yield 82%).

REFERENCE SYNTHETIC EXAMPLE 161 (1s,3R,4r,5S,7s)Aminoadamantanol Benzyl [(1R,2r,3S,5s,7s)hydroxyadamantanyl]carbamate (2.24 g, 7.46 mmol) obtained in Reference Synthetic Example 159b and 5% palladium-carbon (700 mg) in methanol (30 mL) were stirred at room temperature for one day under a hydrogen atmosphere. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give the title compound as a colorless solid (1.29 g, quantitative yield).

REFERENCE SYNTHETIC EXAMPLE 162 tert-Butyl 3-oxoazetidinecarboxylate tert-Butyl 3-hydroxyazetidinecarboxylate (4.02 g, 23.2 mmol) in dichloromethane (305 mL) was mixed with Dess-Martin Periodinane (9.55 g, 22.5 mmol) under cooling with ice and then stirred at room temperature for 3 hours. After addition of 10% aqueous sodium thiosulfate and saturated aqueous sodium hydrogen carbonate under cooling with ice, the reaction mixture was extracted with chloroform, and the 40 organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 2/1 (v/v)) to give the title compound as a colorless solid (3.39 g, yield 85%).

REFERENCE SYNTHETIC EXAMPLE 163 45 tert-Butyl 3-(cyanomethylene)azetidinecarboxylate Diethyl cyanomethylphosphonate (3.54 g, 20.0 mmom) in tetrahydrofuran (20 mL) was added to potassium tert-butoxide (2.03 g, 21.1 mmol) in tetrahydrofuran (30 mL) under cooling with ice and stirred for 30 minutes. The reaction mixture was mixed with tert-butyl 3-oxoazetidinecarboxylate （2.96 g, 17.3 mmol ） in tetrahydrofuran (15 mL) and stirred at room temperature for 1 day, and after addition of water, extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure.

The resulting residue was purified by silica gel column chromatography (hexane / ethyl acetate = 3/1 (v/v)) to give the title compound as a colorless solid (1.93 g, yield 58%).

REFERENCE SYNTHETIC EXAMPLE 164 tert-Butyl 3-(cyanomethyl)azetidinecarboxylate tert-Butyl 3-(cyanomethylene)azetidinecarboxylate (823 mg, 4.24 mmol) in a mixture of methanol (20 mL) and 1,4-dioxane (10 mL) was stirred with 5% palladium- carbon (129 mg) for one day under a hydrogen atmosphere. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane / ethyl acetate = 1/1 (v/v)) to give the title compound as a colorless oil (657 mg, yield 79%).

REFERENCE SYNTHETIC EXAMPLE 165 2-(Azetidinyl)acetonitrile hydrochloride tert-Butyl 3-(cyanomethyl)azetidinecarboxylate (621 mg, 3.17 mmol) in 1,4- dioxane (4 mL) was stirred with 4 M hydrogen chloride - 1,4-dioxane solution (6 mL) at room temperature for 1 day. The reaction mixture was concentrated under reduced pressure to give the title compound as a colorless oil (543 mg, quantitative yield).

REFERENCE SYNTHETIC EXAMPLE 166 4-{[trans(Hydroxymethyl)cyclohexyl]amino}{[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[2,3-b]pyridinecarboxamide 4-Chloro{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine carboxamide (680 mg, 2.09 mmol) obtained in Reference Synthetic Example 88 in N,N-dimethylacetamide (1.1 mL) was mixed with N,N-diisopropylethylamine (1.1 mL) and (transAminocyclohexyl)methanol (945 mg, 7.31 mmol) obtained in Reference Synthetic Example 122 and stirred at 130°C for 3 hours. The reaction mixture was allowed to cool to room temperature and, after addition of saturated aqueous ammonium chloride, extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 5/1 (v/v)) to give the title compound as a colorless solid (781 mg, yield 89%).

REFERENCE SYNTHETIC EXAMPLE 167 1-[trans(Hydroxymethyl)cyclohexyl]{[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidine-2,4(3H,7H)-dione 4-{[trans(Hydroxymethyl)cyclohexyl]amino}{[2-(trimethylsilyl)ethoxy]methyl}- 1H-pyrrolo[2,3-b]pyridinecarboxamide (270 mg, 0.645 mmol) in N,N- dimethylacetamide (3 mL) was mixed with N,N-diisopropylethylamine (3 mL) and 1,1’- 40 carbonyldiimidazole (1.04 g, 6.45 mmol) and stirred at 120°C for 3 hours. The reaction mixture was allowed to cool to room temperature and stirred with 1M aqueous sodium hydroxide (3 mL) and acetonitrile (3 mL) for 5 hours. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was 45 purified by silica gel column chromatography (ethyl acetate / hexane = 9/1 (v/v)) to give the title compound as a colorless solid (206 mg, yield 73%).

REFERENCE SYNTHETIC EXAMPLE 168 trans(2,4-Dioxo{[2-(trimethylsilyl)ethoxy]methyl}-2,3,4,7-tetrahydro-1H- pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidinyl)cyclohexanecarbaldehyde 1-[trans(Hydroxymethyl)cyclohexyl]{[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidine-2,4(3H,7H)-dione (107 mg, 0.240 mmol) in a mixture of toluene (1 mL) and dimethyl sulfoxide (0.25 mL) was mixed with 2- iodoxybenzoic acid (80.9 mg, 0.288 mmol) and stirred at 50°C for 2 hours. After addition of saturated aqueous sodium thiosulfate and saturated aqueous sodium hydrogen carbonate, the reaction mixture was stirred at room temperature for 30 minutes, and extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1/1 →7/3 (v/v)) to give the title compound as a colorless solid (70.1 mg, yield 66%).

REFERENCE SYNTHETIC EXAMPLE 169 1-(4-{[(2,2,2-Trifluoroethyl)amino]methyl}cyclohexyl){[2-(trimethylsilyl)ethoxy]methyl}- 1H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidine-2,4(3H,7H)-dione trans(2,4-Dioxo{[2-(trimethylsilyl)ethoxy]methyl}-2,3,4,7-tetrahydro-1H- pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidinyl)cyclohexanecarbaldehyde (30.4 mg, 0.0680 mmol) in a mixture of methanol (0.5 mL) and acetic acid (50 µL) was stirred with 2,2,2- trifluoroethanamine hydrochloride (12.1 mg, 0.089 mmol) and 2-picoline borane (9.50 mg, 0.089 mmol) at room temperature for 1 day. After addition of 1 M aqueous sodium hydroxide, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure.

The residue was purified by silica gel thin layer chromatography (ethyl acetate / hexane = 1/1 (v/v)) to give the title compound as a colorless solid (32.3 mg, yield 90%).

REFERENCE SYNTHETIC EXAMPLE 170 3-[trans(2,4-Dioxo{[2-(trimethylsilyl)ethoxy]methyl}-2,3,4,7-tetrahydro-1H- pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidinyl)cyclohexyl]acrylonitrile trans(2,4-Dioxo{[2-(trimethylsilyl)ethoxy]methyl}-2,3,4,7-tetrahydro-1H- pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidinyl)cyclohexanecarbaldehyde (34.2 mg, 0.0770 mmol) obtained in Reference Synthetic Example 168 in tetrahydrofuran (2 mL) was mixed with diethyl cyanomethylphosphonate (37 µL, 0.235 mmol) and sodium hydride (55 wt% dispersion in mineral oil, 10 mg, 0.235 mmol) under cooling with ice and then stirred at room temperature for 30 minutes. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1/2 →1/0 (v/v)) to give the title compound as a colorless solid (32.0 mg, yield 92%).

REFERENCE SYNTHETIC EXAMPLES 171 AND 172 40 The reactions in Reference Synthetic Example 89 were carried out in substantially the same manners except that (1s,3R,4r,5S,7s)aminoadamantanol obtained in Reference Synthetic Example 161 or (1s,3R,4s,5S,7s)aminoadamantan- 1-ol obtained in Reference Synthetic Example 160 was used instead of 1-benzyl aminopiperidine to give the compounds of Reference Examples 171 and 172. The 45 names, morphologies and yields of the compounds synthesized are shown in Table 9.

TABLE 9 Rf Compound Name Morphology Yield 4-{[(1R,2r,3S,5s,7s)hydroxyadama ntanyl]amino}{[2-(trimethylsi Brown 171 86% lyl)ethoxy]methyl}-1H-pyrrolo[2,3-b oil ]pyridinecarboxamide 4-{[(1R,2s,3S,5s,7s)hydroxyadama ntanyl]amino}{[2-(trimethylsi Colorless 172 58% lyl)ethoxy]methyl}-1H-pyrrolo[2,3-b oil ]pyridinecarboxamide REFERENCE SYNTHETIC EXAMPLES 173 AND 174 The reactions in Reference Synthetic Example 90 were carried out in substantially the same manners except that 4-{[(1R,2r,3S,5s,7s)hydroxyadamantan- 2-yl]amino}{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinecarboxamide obtained in Reference Synthetic Example 171 or 4-{[(1R,2s,3S,5s,7s) hydroxyadamantanyl]amino}{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- b]pyridinecarboxamide obtained in Reference Synthetic Example 172 was used instead of 4-[(1-benzylpiperidinyl)amino]{[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[2,3-b]pyridinecarboxamide to give the compounds of Reference Synthetic Examples 173 and 174. The names, morphologies and yields of the compounds synthesized are shown in Table 10.

TABLE 10 Rf Compound Name Morphology Yield 1-[(1R,2r,3S,5s,7s)hydroxyadaman tanyl]{[2-(trimethylsilyl)eth Colorless 173 oxy]methyl}-1H-pyrrolo[3',2':5,6]py 95% solid rido[4,3-d]pyrimidine-2,4(3H,7H)-di 1-[(1R,2s,3S,5s,7s)hydroxyadaman tanyl]{[2-(trimethylsilyl)eth Yellow 174 oxy]methyl}-1H-pyrrolo[3',2':5,6]py 99% rido[4,3-d]pyrimidine-2,4(3H,7H)-di REFERENCE SYNTHETIC EXAMPLES 175 AND 176 The reactions in Reference Synthetic Example 97 were carried out in substantially the same manners except that (1s,3R,4r,5S,7s)aminoadamantanol obtained in Reference Synthetic Example 161 or (1s,3R,4s,5S,7s)aminoadamantan- 1-ol obtained in Reference Synthetic Example 160 was used instead of 1- benzylpiperidineamine to give the compounds of Reference Synthetic Examples 175 and 176. The names, morphologies and yields of the compounds synthesized are shown in Table 11.

TABLE 11 Rf Compound Name Morphology Yield 1-(4-{[(1R,2r,3S,5s,7s)hydroxyad amantanyl]amino}{[2-(trimethy Yellow 175 78% lsilyl)ethoxy]methyl}-1H-pyrrolo[2, solid 3-b]pyridinyl)ethanone 1-(4-{[(1R,2s,3S,5s,7s)hydroxyad amantanyl]amino}{[2-(trimethy Yellow 176 91% lsilyl)ethoxy]methyl}-1H-pyrrolo[2, solid 3-b]pyridinyl)ethanone REFERENCE SYNTHETIC EXAMPLES 177 AND 178 The reactions in Reference Synthetic Example 98 were carried out in substantially the same manners except that 1-(4-{[(1R,2r,3S,5s,7s) hydroxyadamantanyl]amino}{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- b]pyridinyl)ethanone obtained in Reference Synthetic Example 175 or 1-(4- {[(1R,2s,3S,5s,7s)hydroxyadamantanyl]amino}{[2-(trimethylsilyl)ethoxy]methyl}- 1H-pyrrolo[2,3-b]pyridinyl)ethanone obtained in Reference Synthetic Example 176 was used instead of 1-{4-[(1-benzylpiperidinyl)amino]{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridinyl}ethanone to give the compounds of Reference Synthetic Examples 177 and 178. The names, morphologies and yields of the compounds synthesized are shown in Table 12.

TABLE 12 Rf Compound Name Morphology Yield 1-[(1R,2r,3S,5s,7s)hydroxyadaman tanyl]{[2-(trimethylsilyl)eth Yellow 177 82% oxy]methyl}-1H-pyrrolo[2,3-h][1,6]n solid aphthyridin-4(7H)-one 1-[(1R,2s,3S,5s,7s)hydroxyadaman tanyl]{[2-(trimethylsilyl)eth Yellow 178 83% oxy]methyl}-1H-pyrrolo[2,3-h][1,6]n solid aphthyridin-4(7H)-one REFERENCE SYNTHETIC EXAMPLE 179 3-Amino-1,1,1-trifluoro(pyridinyl)propanol Isopropylmagnesium chloride-lithium chloride complex - tetrahydrofuran solution (1.3 M, 20.7 mL, 27.0 mmol) was added dropwise to 5-bromochloropyridine (5.20 g, 27.0 mmol) in tetrahydrofuran (40 mL) under cooling with ice, and the reaction mixture was stirred for 30 minutes and then mixed with ethyl 2,2,2-trifluoroacetate (11.5 g, 81.0 mmol) under cooling with ice and stirred at room temperature for 10 minutes. After addition of 1M hydrochloric acid, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a yellow oil. The yellow oil was dissolved in nitromethane (30 mL) and stirred with potassium carbonate (3.73 g, 27.0 mmol) at room temperature for minutes. The reaction mixture was added to 1M hydrochloric acid and extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 3/1 (v/v)) to give a yellow oil. The yellow oil was dissolved in tetrahydrofuran (20 mL), mixed with 10% palladium-carbon (600 mg) and triethylamine (2.60 mL, 18.7 mmol) and then stirred at room temperature for one day under a hydrogen atmosphere. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate → ethyl acetate / methanol / triethylamine = 9/1/1 (v/v/v)) to give the title compound as a colorless solid (913 mg, yield 31%(4 steps)).

SYNTHETIC EXAMPLE 1 1-Cyclohexylmethyl-1,2,4,7-tetrahydropyrrolo[3’,2’:5,6]pyrido[4,3-d][1,3]oxazine Crude 1-cyclohexylmethyl{[2-(trimethylsilyl)ethoxy]methyl}-1,2,4,7- tetrahydropyrrolo[3’,2’:5,6]pyrido[4,3-d][1,3]oxazine (9 mg) obtained in Reference Synthetic Example 23 in N,N-dimethylformamide (1mL) was stirred with ethylenediamine (50 µL, 0.75 mmol) and tetrabutylammonium fluoride (1.0 M tetrahydrofuran solution, 100 µL, 0.100 mmol) at 80°C for 1 hour and allowed to cool to room temperature. After addition of saturated aqueous sodium chloride, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (hexane / ethyl acetate = 1/2 (v/v)) to give the title compound as a colorless amorphous (1.8 mg, yield 29% (two steps)).

SYNTHETIC EXAMPLE 2 1-Cyclohexyl-1,2,4,7-tetrahydropyrrolo[3’,2’:5,6]pyrido[4,3-d][1,3]oxazine 1-Cyclohexyl{[2-(trimethylsilyl)ethoxy]methyl}-1,2,4,7- tetrahydropyrrolo[3’,2’:5,6]pyrido[4,3-d][1,3]oxazine (17 mg, 0.044 mmol) obtained in Reference Synthetic Example 11 in N,N-dimethylformamide (1 mL) was stirred with ethylenediamine (50 µL, 0.75 mmol) and tetrabutylammonium fluoride (1.0 M tetrahydrofuran solution, 120 µL, 0.120 mmol) at 80°C for 2 hours and allowed to cool to room temperature. After addition of saturated aqueous sodium chloride, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (ethyl acetate / methanol = 20/1 (v/v)) to give the title compound as a colorless solid (2.0 mg, yield 18%).

SYNTHETIC EXAMPLE 3 1-Cyclohexyl-1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one 1-Cyclohexyl{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- h][1,6]naphthyridin-4(7H)-one (9 mg, 0.02 mmol) obtained in Reference Synthetic Example 24 in N,N-dimethylformamide (1 mL) was stirred with ethylenediamine (25 µL, 0.37 mmol) and tetrabutylammonium fluoride (1.0 M tetrahydrofuran solution, 70 µL, 0.070 mmol) at 80°C for 30 minutes and allowed to cool to room temperature. After addition of saturated aqueous sodium chloride, the reaction mixture was extracted with 40 ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (ethyl acetate / methanol = 20/1 (v/v)) to give the title compound as a colorless solid (3.3 mg, yield 54%).

SYNTHETIC EXAMPLE 4 45 rac[(3R,4R)Benzylmethylpiperidinyl]-1H-pyrrolo[2,3-h][1,6]naphthyridin- 4(7H)-one rac[(3R,4R)Benzylmethylpiperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}- 1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one (90 mg, 0.18 mmol) obtained in Reference Synthetic Example 35 in N,N-dimethylformamide (3 mL) was stirred with ethylenediamine (50 µL, 0.75 mmol) and tetrabutylammonium fluoride (1.0 M tetrahydrofuran solution, 900 µL, 0.900 mmol) at 80°C for 2 hours and allowed to cool to room temperature. After addition of water, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was mixed with ethyl acetate, and the solid was collected by filtration to give the title compound as a pale orange solid (46.5 mg, yield 70%).

SYNTHETIC EXAMPLE 5 rac[(3R,4R)Methylpiperidinyl]-1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one hydrochloride rac[(3R,4R)Benzylmethylpiperidinyl]-1H-pyrrolo[2,3-h][1,6]naphthyridin- 4(7H)-one (16 mg, 0.043 mmol) and 5% palladium-carbon (15 mg) in methanol (2 mL) was stirred with hydrogen chloride - methanol solution (10 wt%, 20 µL) at 40°C for 2 hours under a hydrogen atmosphere. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give the title compound as a pale yellow solid (15 mg, quantitative yield).

SYNTHETIC EXAMPLE 6 rac[(3R,4R)(2,3-Difluorobenzyl)methylpiperidinyl]-1H-pyrrolo[2,3- h][1,6]naphthyridin-4(7H)-one (Synthetic Example 6a) rac[(3R,4R)-1,4-Dimethylpiperidinyl]-1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one (Synthetic Example 6b) rac[(3R,4R)methylpiperidinyl]-1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)- one hydrochloride (18 mg, 0.057 mmol) and 2,3-difluorobenzaldehyde (10 mg, 0.070 mmol) in a mixture of methanol (1 mL)/acetic acid (1 mL) was stirred with 2-picoline borane (10 mg, 0.094 mmol) at room temperature for one day. After addition of saturated aqueous sodium hydrogen carbonate and 1 M aqueous sodium hydroxide, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (chloroform / methanol = 20/1 (v/v)) to give rac[(3R,4R)(2,3-difluorobenzyl)methylpiperidinyl]-1H-pyrrolo[2,3- h][1,6]naphthyridin-4(7H)-one (less polar fraction: 6.1 mg, yield 26%) as a pale yellow solid and rac[(3R,4R)-1,4-dimethylpiperidinyl]-1H-pyrrolo[2,3-h][1,6]naphthyridin- 4(7H)-one (more polar fraction: 5.9 mg, yield 35%) as a colorless oil.

SYNTHETIC EXAMPLE 7 rac[(3R,4R)Methyl(4-oxo-4,7-dihydro-1H-pyrrolo[2,3-h][1,6]naphthyridin yl)piperidin-1yl]oxopropanenitrile rac[(3R,4R)Methylpiperidinyl]-1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)- one hydrochloride (15 mg, 0.040 mmol) obtained in Synthetic Example 5, 1-(3- 40 dimethylaminopropyl)ethylcarbodiimide hydrochloride (10 mg, 0.052 mmol), N- hydroxybenzotriazole (6 mg, 0.04 mmol), 2-cyanoacetic acid (5 mg, 0.06 mmol) and N,N-diisopropylethylamine (30 µL, 0.017 mmol) in N,N-dimethylformamide (0.5 mL) was stirred at room temperature for 2 hours. After addition of water, the reaction mixture was extracted with chloroform, and the aqueous layer was extracted with a mixture of 45 chloroform/2-propanol. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (ethyl acetate / methanol = 20/1 (v/v)), and the crude product was further purified by silica gel thin layer chromatography (NH-PLC05 plate manufactured by Fuji Silysia Chemical Ltd.: chloroform / methanol = 10/1 (v/v)) to give the title compound as a colorless solid (2.5 mg, yield 17%).

SYNTHETIC EXAMPLE 8 rac[(3R,4R)(2-Cyclopropylacetyl)methylpiperidinyl]-1H-pyrrolo[2,3- h][1,6]naphthyridin-4(7H)-one rac[(3R,4R)Methylpiperidinyl]-1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)- one hydrochloride (20 mg, 0.054 mmol) obtained in Synthetic Example 5, 1-(3- dimethylaminopropyl)ethylcarbodiimide hydrochloride (20 mg, 0.10 mmol), 2- cyclopropylacetic acid (10 µL) and N,N-diisopropylethylamine (26 µL, 0.015 mmol) in N,N-dimethylformamide (1 mL) was stirred at room temperature for 6 hours. After addition of saturated aqueous sodium hydrogen carbonate, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (chloroform / methanol = 15/1 (v/v)), and the crude product was further purified by silica gel thin layer chromatography (NH-PLC05 plate manufactured by Fuji Silysia Chemical Ltd.: chloroform / methanol = 30/1 (v/v)) to give the title compound as a colorless solid (7.9 mg, yield 40%).

SYNTHETIC EXAMPLE 9 rac[(3R,4R)Methyl(3,3,3-trifluoropropanoyl)piperidinyl]-1H-pyrrolo[2,3- h][1,6]naphthyridin-4(7H)-one rac[(3R,4R)Methylpiperidinyl]-1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)- one hydrochloride (15.6 mg, 0.0489 mmol) obtained in Synthetic Example 5, 1-(3- dimethylaminopropyl)ethylcarbodiimide hydrochloride (12.5 mg, 0.0978 mmol), 3,3,3- trifluoropropionic acid (13 µL, 0.098 mmol) and N,N-diisopropylethylamine (26 µL, 0.015 mmol) in N,N-dimethylformamide (1 mL) was stirred at room temperature for one day.

After addition of saturated aqueous sodium hydrogen carbonate, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (chloroform / methanol = 4/1 (v/v)) to give the title compound as a colorless solid (12.2 mg, yield 64%).

SYNTHETIC EXAMPLE 10 rac[(3R,4R)(Isobutylsulfonyl)methylpiperidinyl]-1H-pyrrolo[2,3- h][1,6]naphthyridin-4(7H)-one rac[(3R,4R)(Isobutylsulfonyl)methylpiperidinyl]{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one (18 mg, 0.034 mmol) obtained in Reference Synthetic Example 37 in dichloromethane (1 mL) was stirred with trifluoroacetic acid (1 mL) at room temperature for 3 hours. After addition of saturated aqueous sodium hydrogen carbonate, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous sodium 40 sulfate and concentrated under reduced pressure. The residue was dissolved in a mixture of dichloromethane (1 mL) and methanol (1 mL) and stirred with ethylenediamine (100 µL, 1.50 mmol) and 1 M aqueous sodium hydroxide (100 µL, 0.100 mmol) at room temperature for one day. After addition of water, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous 45 sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (ethyl acetate / methanol = 20/1 (v/v)) to give the title compound as a colorless solid (8.2 mg, yield 60%).

SYNTHETIC EXAMPLE 11 rac[(3R,4R)Methyl(2,2,2-trifluoroethylsulfonyl)piperidinyl]-1H-pyrrolo[2,3- h][1,6]naphthyridin-4(7H)-one rac[(3R,4R)Methylpiperidinyl]-1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)- one hydrochloride (16 mg, 0.050 mmol) obtained in Synthetic Example 5 in a mixture of dichloromethane (1 mL) and N,N-dimethylformamide (100 µL) was mixed with N,N- diisopropylethylamine (30 µL, 0.17 mmol) and 2,2,2-trifluoroethanesulfonyl chloride (20 mg, 0.11 mmol) under cooling with ice and stirred at room temperature for one day.

After addition of saturated aqueous sodium hydrogen carbonate, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (ethyl acetate / methanol = 10/1 (v/v)) to give the title compound as a colorless solid (2.5 mg, yield 12%).

SYNTHETIC EXAMPLE 12 1-Cyclohexyl-1,4-dihydropyrrolo[3’,2’:5,6]pyrido[3,4-b][1,4]thiazine-4,4(7H)-dione Crude 1-cyclohexyl{[2-(trimethylsilyl)ethoxy]methyl}-1,4- dihydropyrrolo[3’,2’:5,6]pyrido[3,4-b][1,4]thiazine-4,4(7H)-dione (8.5 mg) obtained in Reference Synthetic Example 28 in dichloromethane (1 mL) was stirred with trifluoroacetic acid (1 mL) at room temperature for 3 hours. After addition of saturated aqueous sodium hydrogen carbonate, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in methanol (1 mL) and stirred with ethylenediamine (20 µL, 0.30 mmol) and 1 M aqueous sodium hydroxide (20 µL, 0.020 mmol) at room temperature for 3 hours. The precipitated solid was collected by filtration to give the title compound as a colorless solid (1.7 mg, yield 39% (two steps)).

SYNTHETIC EXAMPLE 13 1-Cyclohexyl-1H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidin-4(7H)-one 1-Cyclohexyl{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[3',2':5,6]pyrido[4,3- d]pyrimidin-4(7H)-one (9 mg, 0.02 mmol) obtained in Reference Synthetic Example 32 in dichloromethane (2 mL) was stirred with trifluoroacetic acid (1 mL) at room temperature for 2 hours. After addition of saturated aqueous sodium hydrogen carbonate, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure.

The resulting residue was dissolved in methanol (2 mL) and dichloromethane (1 mL) and stirred with ethylenediamine (50 µL, 0.75 mmol) and 1 M aqueous sodium hydroxide (50 µL, 0.050 mmol) at room temperature for 3 days. After addition of water, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (chloroform / methanol = 30/1 (v/v)) to 40 give the title compound as a colorless solid (2.1 mg, yield 35%).

SYNTHETIC EXAMPLE 14 rac[(3R,4R)Benzylmethylpiperidinyl]-1,2,4,7- tetrahydropyrrolo[3’,2’:5,6]pyrido[4,3-d][1,3]oxazine rac[(3R,4R)Benzylmethylpiperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}- 45 1,2,4,7-tetrahydropyrrolo[3’,2’:5,6]pyrido[4,3-d][1,3]oxazine (64.6 mg, 0.131 mmol) obtained in Reference Synthetic Example 41 in dichloromethane (2 mL) was stirred with trifluoroacetic acid (1 mL) at room temperature for 2 hours, and the reaction mixture was concentrated under reduced pressure. The resulting residue was stirred with dichloromethane (4mL), methanol (2 mL), ethylenediamine (200 µL, 3.00 mmol) and 1 M aqueous sodium hydroxide (2 mL, 2 mmol) at room temperature for 1 hour. The reaction solution was concentrated under reduced pressure, and after addition of water, extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (chloroform / methanol = 10/1 (v/v)) to give the title compound as a pale yellow amorphous (28.2 mg, yield 59%).

SYNTHETIC EXAMPLE 15 rac[(3R,4R)Methylpiperidinyl]-1,2,4,7-tetrahydropyrrolo[3’,2’:5,6]pyrido[4,3- d][1,3]oxazine rac[(3R,4R)Benzylmethylpiperidinyl]-1,2,4,7- tetrahydropyrrolo[3’,2’:5,6]pyrido[4,3-d][1,3]oxazine (28.2 mg, 0.0777 mmol) in ethanol was stirred with 5% palladium-carbon (30 mg) and concentrated hydrochloric acid (2 drops) at 50°C for 2 hours under a hydrogen atmosphere. The reaction mixture was allowed to cool to room temperature and filtered, and the filtrate was concentrated under reduced pressure to give the title compound (21.2 mg, yield 100%).

SYNTHETIC EXAMPLE 16 rac[(3R,4R)Methyl(pyrrolo[3',2':5,6]pyrido[4,3-d][1,3]oxazin-1(2H,4H,7H)- yl)piperidinyl]oxopropanenitrile rac[(3R,4R)Methylpiperidinyl]-1,2,4,7- tetrahydropyrrolo[3’,2’:5,6]pyrido[4,3-d][1,3]oxazine (21.2 mg, 0.0777 mmol) in N,N- dimethylformamide was stirred with cyanoacetic acid (15 mg, 0.18 mmol), O-(7- azabenzotriazolyl)-N,N,N’,N’-tetramethyluronium hexafluorophosphate (67 mg, 0.18 mmol), N,N-diisopropylethylamine (44.9 µL, 0.264 mmol) at room temperature for one day. After addition of water, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (Hi Flash column amino type manufactured by Yamazen Corporation: chloroform / methanol =20/1 (v/v)) to give the title compound as a yellow oil (3 mg, yield 10%).

SYNTHETIC EXAMPLE 17 1-Cyclohexyl-3,4-dihydro-1H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidin-2(7H)-one 1-Cyclohexyl{[2-(trimethylsilyl)ethoxy]methyl}-3,4-dihydro-1H- pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidin-2(7H)-one (46.6 mg, 0.116 mmol) obtained in Reference Synthetic Example 13 in dichloromethane (3 mL) was stirred with trifluoroacetic acid (1 mL) at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was stirred with dichloromethane (2 mL), methanol (1 mL), ethylenediamine (200 µL, 3.00 mmol) and 1 M aqueous sodium hydroxide (1 mL, 1 mmol) for one day. The reaction mixture was 40 concentrated under reduced pressure, and after addition of water, extracted with chloroform, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give the title compound as a colorless solid (22.2 mg, yield 70%).

SYNTHETIC EXAMPLE 18 45 1-Cyclohexyl-1H-pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidin-2(7H)-one 1-Cyclohexyl-3,4-dihydro-1H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidin-2(7H)-one (18 mg, 0.066 mmol) in chloroform (2 mL) was stirred with manganese dioxide (100 mg, 1.15 mmol) at 50°C for 5 hours. The reaction mixture was filtered, and the filtrate was purified by silica gel column chromatography (Hi Flash column amino type manufactured by Yamazen Corporation: chloroform / methanol = 10/1 (v/v)) to give the title compound as a colorless solid (0.58 mg, yield 3.2%).

SYNTHETIC EXAMPLE 19 1-Cyclohexyl-1,4-dihydro-7H-pyrrolo[3’,2’:5,6]pyrido[3,4-e]pyrimidine 1-Cyclohexyl-1,4-dihydro{[2-(trimethylsilyl)ethoxy]methyl}- pyrrolo[3’,2’:5,6]pyrido[3,4-e]pyrimidine (48.8 mg, 0.127 mmol) obtained in Reference Synthetic Example 14 in dichloromethane (2 mL) was stirred with trifluoroacetic acid (1 mL) for one day. The reaction mixture was concentrated under reduced pressure and stirred with dichloromethane (2 mL), methanol (1 mL), ethylenediamine (300 µL, 4.49 mmol) and 1 M aqueous sodium hydroxide (1 mL, 1 mmol) for one day. The reaction mixture was concentrated under reduced pressure and extracted with chloroform, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Hi Flash column amino type manufactured by Yamazen Corporation: chloroform / methanol = 10/1 (v/v)) to give the title compound as a colorless solid (11 mg, yield 34%).

SYNTHETIC EXAMPLE 20 9-Cyclohexyl-3H-imidazo[4,5-h][1,6]naphthyridin-6(9H)-one 9-Cyclohexyl{[2-(trimethylsilyl)ethoxy]methyl}-3H-imidazo[4,5- h][1,6]naphthyridin-6(9H)-one (57.5 mg, 0.144 mmol) obtained in Reference Synthetic Example 48 in dichloromethane (2 mL) was stirred with trifluoroacetic acid (2mL) at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and the resulting residue was stirred with dichloromethane (4 mL), methanol (1 mL), ethylenediamine (200 µL, 3.00 mmol) and 1 M aqueous sodium hydroxide (1 mL, 1 mmol) at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by silica gel chromatography (chloroform / methanol = 10/1 (v/v)) to give the title compound as a pale yellow solid (23.0 mg, yield 59%).

SYNTHETIC EXAMPLES 21 TO 47 The reactions in Synthetic Example 10 were carried out in substantially the same manners except that the compounds obtained in Reference Synthetic Examples 51, 54, 59 to 71, 73 or 75 to 85 were used instead of rac[(3R,4R)(isobutylsulfonyl) methylpiperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- h][1,6]naphthyridin-4(7H)-one to give the compounds of Synthetic Examples 21 to 47.

The names, morphologies and yields of the compounds synthesized are shown in Tables 13 to 15.

TABLE 13 TABLE 14 TABLE 15 SYNTHETIC EXAMPLE 48 1-{1-[4-(tert-Butyl)cyclohexanecarbonyl]methylpiperidinyl}-1H-pyrrolo[2,3- h][1,6]naphthyridin-4(7H)-one The reactions in Synthetic Example 10 were carried out in substantially the same manners except that Reference Synthetic Examples 86a or 86b obtained in Reference Synthetic Example 86 were used instead of rac[(3R,4R)(isobutylsulfonyl) methylpiperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- h][1,6]naphthyridin-4(7H)-one to give the two isomers of the title compound, Synthetic Example 48a (colorless amorphous, 5.0 mg, 71%) or Synthetic Example 48b (colorless amorphous, 4.1 mg, yield 56%).

SYNTHETIC EXAMPLES 49 TO 53 The reactions in Synthetic Example 10 were carried out in substantially the same manners except that the compounds obtained in Reference Synthetic Examples 90 and 92 to 95 were used instead of rac[(3R,4R)(isobutylsulfonyl)methylpiperidin- 3-yl]{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one to give the compounds of Synthetic Examples 49 to 53. The names, morphologies and yields of the compounds synthesized are shown in Table 16.

TABLE 16 SYNTHETIC EXAMPLES 54 TO 58 The reactions in Synthetic Example 10 were carried out in substantially the same manners except that the compounds obtained in Reference Synthetic Examples 98 and 100 to 103 were used instead of rac[(3R,4R)(isobutylsulfonyl) methylpiperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- h][1,6]naphthyridin-4(7H)-one to give the compounds of Synthetic Examples 54 to 58.

The names, morphologies and yields of the compounds synthesized are shown in Table 17.

TABLE 17 SYNTHETIC EXAMPLES 59 TO 67 The reactions in Synthetic Example 10 were carried out in substantially the same manners except that the compounds obtained in Reference Synthetic Examples 108 and 110 to 116 and 121 were used instead of rac[(3R,4R)(isobutylsulfonyl) methylpiperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- h][1,6]naphthyridin-4(7H)-one to give the compounds of Synthetic Examples 59 to 67.

The names, morphologies and yields of the compounds synthesized are shown in Table 18.

TABLE 18 SYNTHETIC EXAMPLE 68 1-(Piperidinyl)-3,4-dihydro-1H-pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidin-2(7H)-one 1-(1-Benzylpiperidinyl)-3,4-dihydro-1H-pyrrolo[3’,2’:5,6]pyrido[4,3-d]pyrimidin- 2(7H)-one (25.6 mg, 0.0708 mmol) obtained in Synthetic Example 59 and 5% palladium-carbon (30 mg) in ethanol was stirred with 10 wt% hydrogen chloride- methanol (2 drops) at 50°C for 2 hours under a hydrogen atmosphere. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give the title compound as a colorless solid (9 mg, yield 46%).

SYNTHETIC EXAMPLES 69 TO 85 The reactions in Synthetic Example 10 were carried out in substantially the same manners except that the compounds obtained in Reference Synthetic Examples 124 and 128 to 144 were used instead of rac[(3R,4R)(isobutylsulfonyl) methylpiperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- h][1,6]naphthyridin-4(7H)-one to give the compounds of Synthetic Examples 69 to 85.

The names, morphologies and yields of the compounds synthesized are shown in Tables 19 and 20.

TABLE 19 Ex Compound Name Morphology Yield 1-(trans(hydroxymethyl)cycloh pale yellow 69 exyl)-1H-pyrrolo[2,3-h][1,6]naph 38% solid thyridin-4(7H)-one 1-(transmethoxycyclohexyl)-1H 70 -pyrrolo[2,3-h][1,6]naphthyridin brown solid 42% -4(7H)-one 1-(1-{[5-(trifluoromethyl)furan- 2-yl]methyl}piperidinyl)-1H-p 71 yellow solid quant yrrolo[2,3-h][1,6]naphthyridin-4 (7H)-one 1-{1-[(5-nitrofuranyl)methyl] 72 Yellow oil 33% piperidinyl}-1H-pyrrolo[2,3-h ][1,6]naphthyridin-4(7H)-one ethyl -{[4-(4-oxo-4,7-dihydro-1H-pyrr yellow 73 olo[2,3-h][1,6]naphthyridinyl quant amorphous )piperidinyl]methyl}furanc arboxylate 1-[1-(3,4-difluorobenzyl)piperid 74 inyl]-1H-pyrrolo[2,3-h][1,6]n Yellow oil 80% aphthyridin-4(7H)-one 1-[1-(3,4-dichlorobenzyl)piperid 75 inyl]-1H-pyrrolo[2,3-h][1,6]n yellow solid quant aphthyridin-4(7H)-one 1-(1-{[6-(trifluoromethyl)pyridi nyl]methyl}piperidinyl)-1H 76 yellow solid quant -pyrrolo[2,3-h][1,6]naphthyridin -4(7H)-one 1-{1-[(2-chlorothiazolyl)meth 77 yl]piperidinyl}-1H-pyrrolo[2, Yellow oil 69% 3-h][1,6]naphthyridin-4(7H)-one 1-{1-[4-fluoro(trifluoromethy l)benzyl]piperidinyl}-1H-pyrr 78 yellow solid 96% olo[2,3-h][1,6]naphthyridin-4(7H )-one 1-{1-[(5-nitrothiophenyl)meth 79 brown solid 27% yl]piperidinyl}-1H-pyrrolo[2, 3-h][1,6]naphthyridin-4(7H)-one 1-{1-[(5-bromofuranyl)methyl] 80 piperidinyl}-1H-pyrrolo[2,3-h yellow solid quant ][1,6]naphthyridin-4(7H)-one 1-{1-[(5-bromothiophenyl)meth 81 yl]piperidinyl}-1H-pyrrolo[2, yellow solid quant 3-h][1,6]naphthyridin-4(7H)-one 1-{1-[(4-bromothiophenyl)meth 82 yl]piperidinyl}-1H-pyrrolo[2, yellow solid quant 3-h][1,6]naphthyridin-4(7H)-one TABLE 20 SYNTHETIC EXAMPLE 86 1-{1-[(2-Methylthiazolyl)methyl]piperidinyl}-1H-pyrrolo[2,3-h][1,6]naphthyridin- 4(7H)-one 1-(Piperidinyl){[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3- h][1,6]naphthyridin-4(7H)-one (30 mg, 0.075 mmol) obtained in Reference Synthetic Example 99 in dichloromethane was stirred with 4-(chloromethyl)methylthiazole hydrochloride (13.3 mg, 0.0901 mmol) and triethylamine (16 µL, 0.11 mmol) at 40°C for one day. After addition of water, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was roughly purified by silica gel column chromatography (chloroform / methanol = 9/1 (v/v)), and the resulting crude product was dissolved in dichloromethane (2 mL) and stirred with trifluoroacetic acid (1mL) at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in a mixture of dichloromethane (2 mL) and methanol (1 mL) and stirred with ethylenediamine (200 µL) and 1 M aqueous sodium hydroxide (1 mL) for one day. After addition of water, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give the title compound as a brown oil (6.3 mg, yield 22%).

SYNTHETIC EXAMPLE 87 1-[1-(5-Chlorothiophenecarbonyl)piperidinyl]-1H-pyrrolo[2,3-h][1,6]naphthyridin- 4(7H)-one 1-[1-(5-Chlorothiophenecarbonyl)piperidinyl]{[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one obtained in Reference Synthetic Example 144 in dichloromethane (2 mL) was stirred with trifluoroacetic acid (1 mL) at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in a mixture of dichloromethane (2 mL) and methanol (1 mL) and stirred with ethylenediamine (200 µL) and 1 M aqueous sodium hydroxide (1 mL) for one day. The precipitated solid was collected by filtration to give the title compound as a colorless solid (22.8 mg, yield 73%).

SYNTHETIC EXAMPLES 88 TO 107 The reactions in Synthetic Example 14 were carried out in substantially the same manners except that the compounds obtained in Reference Synthetic Examples 145 to 157, 167, 169, 170, 173, 174, 177 or 178 were used instead of rac[(3R, 4R) Benzylmethylpiperidinyl]{[2-(trimethylsilyl)ethoxy]methyl}-1,2,4,7-tetrahydro- pyrrolo[3’, 2’:5,6]pyrido[4,3-d][1,3]oxazine to give the compounds of Synthetic Examples 88 to 107. The names, morphologies and yields of the compounds synthesized are shown in Tables 21 and 22.

TABLE 21 Ex Compound Name Morphology Yield 1-[1-(2-aminoethyl)piperidinyl]- 88 1H-pyrrolo[3',2':5,6]pyrido[4,3-d]p brown solid 90% yrimidine-2,4(3H,7H)-dione 1-{1-[(5-bromothiophenyl)methyl] piperidinyl}-1H-pyrrolo[3',2':5, 89 Colorless solid 77% 6]pyrido[4,3-d]pyrimidine-2,4(3H,7H )-dione 1-{1-[2-(tetrahydro-2H-thiopyran yl)ethyl]piperidinyl}-1H-pyrrolo 90 Colorless solid 26% [3',2':5,6]pyrido[4,3-d]pyrimidine- 2,4(3H,7H)-dione 1-[1-(cyclopropylmethyl)piperidin-4 91 -yl]-1H-pyrrolo[3',2':5,6]pyrido[4, Colorless solid 24% 3-d]pyrimidine-2,4(3H,7H)-dione 1-[1-(2-methylbutyl)piperidinyl] 92 -1H-pyrrolo[3',2':5,6]pyrido[4,3-d] Colorless solid 4% pyrimidine-2,4(3H,7H)-dione 1-{1-[2-(tetrahydro-2H-pyranyl)e thyl]piperidinyl}-1H-pyrrolo[3', 93 Colorless solid 13% 2':5,6]pyrido[4,3-d]pyrimidine-2,4( 3H,7H)-dione 2-[4-(2,4-dioxo-2,3,4,7-tetrahydro- 1H-pyrrolo[3',2':5,6]pyrido[4,3-d]p 94 Colorless solid 3% yrimidinyl)piperidinyl]aceton itrile 1-[1-(2,2,2-trifluoroethyl)piperidi 95 nyl]-1H-pyrrolo[3',2':5,6]pyrido Colorless solid 38% [4,3-d]pyrimidine-2,4(3H,7H)-dione -[4-(2,4-dioxo-2,3,4,7-tetrahydro- 1H-pyrrolo[3',2':5,6]pyrido[4,3-d]p 96 Colorless solid 88% yrimidinyl)piperidinyl]pentan enitrile 1-[1-(6,6,6-trifluorohexyl)piperidi 97 nyl]-1H-pyrrolo[3',2':5,6]pyrido Colorless solid 29% [4,3-d]pyrimidine-2,4(3H,7H)-dione 4-[4-(2,4-dioxo-2,3,4,7-tetrahydro- 1H-pyrrolo[3',2':5,6]pyrido[4,3-d]p 98 Colorless solid 4% yrimidinyl)piperidinyl]butane nitrile TABLE 22 Ex Compound Name Morphology Yield 1-{1-[(tetrahydrofuranyl)methyl]pipe Colorless 99 ridinyl}-1H-pyrrolo[3',2':5,6]pyrido 40% solid [4,3-d]pyrimidine-2,4(3H,7H)-dione 3-[4-(2,4-dioxo-2,3,4,7-tetrahydro-1H-p Colorless 100 43% yrrolo[3',2':5,6]pyrido[4,3-d]pyrimidin solid yl)piperidinyl]propanenitrile 1-[trans(hydroxymethyl)cyclohexyl]-1 Colorless 101 H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimi 74% solid dine-2,4(3H,7H)-dione 1-(trans{[(2,2,2-trifluoroethyl)amin o]methyl}cyclohexyl)-1H-pyrrolo[3',2':5 Colorless 102 75% ,6]pyrido[4,3-d]pyrimidine-2,4(3H,7H)-d solid ione 3-[trans(2,4-dioxo-2,3,4,7-tetrahydr Colorless 103 o-1H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyr 53% solid imidinyl)cyclohexyl]acrylonitrile 1-((1R,2r,3S,5s,7s)hydroxyadamantan- Colorless 104 2-yl)-1H-pyrrolo[3',2':5,6]pyrido[4,3-d 41% solid ]pyrimidine-2,4(3H,7H)-dione 1-((1R,2s,3S,5s,7s)hydroxyadamantan- Brown 105 2-yl)-1H-pyrrolo[3',2':5,6]pyrido[4,3-d 25% ]pyrimidine-2,4(3H,7H)-dione 1-((1R,2r,3S,5s,7s)hydroxyadamantan- Colorless 106 2-yl)-1H-pyrrolo[2,3-h][1,6]naphthyridi 55% solid n-4(7H)-one 1-((1R,2s,3S,5s,7s)hydroxyadamantan- Colorless 107 2-yl)-1H-pyrrolo[2,3-h][1,6]naphthyridi 69% solid n-4(7H)-one SYNTHETIC EXAMPLE 108 1-[1-(2-Morpholinoethyl)piperidinyl]-1H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidine- 2,4(3H,7H)-dione 1-(Piperidinyl){[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[3',2':5,6]pyrido[4,3- d]pyrimidine-2,4(3H,7H)-dione hydrochloride (30.0 mg, 0.0664 mmol) obtained in Reference Synthetic Example 91 and 4-(2-chloroethyl)morpholine hydrochloride (36.8 mg, 0.198 mmol) in acetonitrile (1.5 mL) were mixed with N,N-diisopropylethylamine (79.5 µL, 0.462 mmol) and stirred at 60°C for 15 hours and then with 4-(2- chloroethyl)morpholine hydrochloride (36.8 mg, 0.198 mmol) and N,N- diisopropylethylamine (34.1 µL, 0.198 mmol) for 30.5 hours. The reaction mixture was allowed to cool to room temperature and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (methanol / chloroform = 3/97 → 12/88 (v/v)). The resulting crude product was dissolved in dichloromethane (1.5 mL) and stirred with trifluoroacetic acid (0.5 mL) at room temperature for 2 hours. The reaction mixture was azeotropically distilled with toluene under reduced pressure, and the residue was dissolved in methanol (2 mL) and stirred with ethylenediamine (75 µL, 1.12 mmol) and 1 M aqueous sodium hydroxide (0.8 mL) at room temperature for 2.5 hours. The reaction mixture was concentrated under reduced pressure and, after addition of water, extracted with 1-butanol four times. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (Hi Flash column amino type manufactured by Yamazen Corporation: methanol / chloroform = 0/1 → 9/91 (v/v)) to give the title compound as a colorless solid (1.5 mg, yield 6% (three steps)).

SYNTHETIC EXAMPLE 109 tert-Butyl 4-({2-[4-(2,4-dioxo-2,3,4,7-tetrahydro-1H-pyrrolo[3',2':5,6]pyrido[4,3- d]pyrimidinyl)piperidinyl]ethyl}amino)piperidinecarboxylate 1-[1-(2-Aminoethyl)piperidinyl]-1H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidine- 2,4(3H,7H)-dione (20.0 mg, 0.0609 mmol) obtained in Synthetic Example 88 and tert- butyl 4-oxopiperidinecarboxylate (24.3 mg, 0.122 mmol) in a mixture of methanol (1 mL) and acetic acid (100 µL) were stirred with 2-picoline borane (13.0 mg, 0.122 mmol) at room temperature for 17 hours. The reaction mixture was basified with 1 M aqueous sodium hydroxide and extracted with a mixture of chloroform and 2-propanol four times.

The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methanol / chloroform = 0/1 → 1/0 (v/v)) to give the title compound as a colorless solid (18.0 mg, yield 57%).

SYNTHETIC EXAMPLE 110 1-(1-{2-[(Cyclopropylmethyl)amino]ethyl}piperidinyl)-1H-pyrrolo[3',2':5,6]pyrido[4,3- d]pyrimidine-2,4(3H,7H)-dione The reactions in Synthetic Example 109 were carried out in substantially the same manners except that cyclopropanecarbaldehyde was used instead of tert-butyl 4- oxopiperidinecarboxylate to give the title compound as a colorless solid (5.5 mg, yield 23%).

SYNTHETIC EXAMPLE 111 1-{1-[2-(Piperidinylamino)ethyl]piperidinyl}-1H-pyrrolo[3',2':5,6]pyrido[4,3- d]pyrimidine-2,4(3H,7H)-dione tert-Butyl 4-({2-[4-(2,4-dioxo-2,3,4,7-tetrahydro-1H-pyrrolo[3',2':5,6]pyrido[4,3- d]pyrimidinyl)piperidinyl]ethyl}amino)piperidinecarboxylate (16.9 mg, 0.0330 mmol) obtained in Synthetic Example 109 in a mixture of dichloromethane (1 mL) and methanol (1 mL) was stirred with trifluoroacetic acid (100 µL, 1.31 mmol) at room temperature for 2.5 hours and then with trifluoroacetic acid (400 µL, 5.23 mmol) at room temperature for 2.5 hours and then with trifluoroacetic acid (500 µL, 6.53 mmol) at room temperature for 4.5 hours and then with trifluoroacetic acid (2 mL, 26.1 mmol) at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by silica gel chromatography (Hi Flash column amino type manufactured by Yamazen Corporation: methanol / ethyl acetate = 40 1/4 → 4/1 (v/v)) to give the title compound as a colorless solid (4.21 mg, yield 30%).

SYNTHETIC EXAMPLE 112 1-{trans[((R)Hydroxypyrrolidinyl)methyl]cyclohexyl}-1H- pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidine-2,4(3H,7H)-dione trans(2,4-Dioxo{[2-(trimethylsilyl)ethoxy]methyl}-2,3,4,7-tetrahydro-1H- 45 pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidinyl)cyclohexanecarbaldehyde (30.0 mg, 0.067 mmol) obtained in Reference Synthetic Example 168 in a mixture of methanol (0.5 mL) and acetic acid (50 µL) was stirred with (R)hydroxy-pyrrolidine (14.3 mg, 0.088 mmol) and 2-picoline borane (9.4 mg, 0.088 mmol) at room temperature for 1 day. After addition of 1M aqueous sodium hydroxide, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel thin layer chromatography (ethyl acetate / methanol = 10/1 (v/v)) to give the compound as a colorless solid. The resulting colorless solid was dissolved in dichloromethane (1.0 mL) and stirred with trifluoroacetic acid (0.4 mL) at room temperature for 5 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was stirred with methanol (0.7 mL), ethylenediamine (30 µL) and 1 M aqueous sodium hydroxide (30 µL) at room temperature for 1 day. The reaction mixture was filtered and the resulting solid was washed with water and methanol to give the title compound as a colorless solid (20.0 mg, yield 52% (three steps)).

SYNTHETIC EXAMPLES 113 TO 132 The reactions in Synthetic Example 112 were carried out in substantially the same manners except that 3-hydroxyazetidine hydrochloride, thiomorpholine-1,1- dioxide, 4,4-difluoropiperidine, 3,3'-iminodipropionitrile, cyclopropylmethylamine, (R) cyanopyrrolidine, 3,3-dimethylazetidine, 2-methylaminoethanol, 2-(phenylmethyl)amino- ethanol, 1-trifluoromethylcyclopropylamine, N-(2-aminoethyl)morpholine, 2-(azetidin- 3-yl)acetonitrile hydrochloride, 2,2-dimethylcyclopropylamine hydrochloride, 1- aminomethylcyclohexanol, aminoacetonitrile hydrochloride, 4-trifluoromethylpiperidine, 3-(trifluoromethyl)azetidinol hydrochloride, tetrahydrofurylmethylamine, 2- methoxyethanamine or 3-amino-1,1,1-trifluoro(pyridinyl)propanol obtained in Reference Synthetic Example 179 were used instead of (R)hydroxy-pyrrolidine to give the compounds of Synthetic Examples 113 to 132. The names, morphologies and yields of the compounds synthesized are shown in Tables 23 and 24.

TABLE 23 Ex Compound Name Morphology Yield 1-{trans[(3-hydroxyazetidinyl)m ethyl]cyclohexyl}-1H-pyrrolo[3',2':5, Colorless 62% 6]pyrido[4,3-d]pyrimidine-2,4(3H,7H)- solid (3steps) dione 1-{trans[(1,1-dioxidothiomorpholin o)methyl]cyclohexyl}-1H-pyrrolo[3',2' Colorless 33% :5,6]pyrido[4,3-d]pyrimidine-2,4(3H,7 solid (3steps) H)-dione 1-{trans[(4,4-difluoropiperidin yl)methyl]cyclohexyl}-1H-pyrrolo[3',2 Colorless 68% ':5,6]pyrido[4,3-d]pyrimidine-2,4(3H, solid (3steps) 7H)-dione 3,3'-({[trans(2,4-dioxo-2,3,4,7-te trahydro-1H-pyrrolo[3',2':5,6]pyrido[ Colorless 63% 4,3-d]pyrimidinyl)cyclohexyl]methy solid (3steps) l}azanediyl)dipropanenitrile 1-(trans{[(cyclopropylmethyl)amino ]methyl}cyclohexyl)-1H-pyrrolo[3',2': Colorless 45% ,6]pyrido[4,3-d]pyrimidine-2,4(3H,7H solid (3steps) )-dione (R){[trans(2,4-dioxo-2,3,4,7-te trahydro-1H-pyrrolo[3',2':5,6]pyrido[ Colorless 63% 4,3-d]pyrimidinyl)cyclohexyl]methy solid (3steps) l}pyrrolidinecarbonitrile 1-{trans[(3,3-dimethylazetidiny l)methyl]cyclohexyl}-1H-pyrrolo[3',2' Brown 47% :5,6]pyrido[4,3-d]pyrimidine-2,4(3H,7 oil (3steps) H)-dione 1-(trans{[(2-hydroxyethyl)(methyl) amino]methyl}cyclohexyl)-1H-pyrrolo[3 Colorless 52% ',2':5,6]pyrido[4,3-d]pyrimidine-2,4( solid (3steps) 3H,7H)-dione 1-(trans{[benzyl(2-hydroxyethyl)am ino]methyl}cyclohexyl)-1H-pyrrolo[3', Colorless 56% 2':5,6]pyrido[4,3-d]pyrimidine-2,4(3H solid (3steps) ,7H)-dione 1-[trans({[1-(trifluoromethyl)cycl opropyl]amino}methyl)cyclohexyl]-1H-p Colorless 43% yrrolo[3',2':5,6]pyrido[4,3-d]pyrimid solid (3steps) ine-2,4(3H,7H)-dione TABLE 24 Ex Compound Name Morphology Yield 1-(trans{[(2-morpholinoethyl)amino ]methyl}cyclohexyl)-1H-pyrrolo[3',2': Colorless 17% ,6]pyrido[4,3-d]pyrimidine-2,4(3H,7H solid (3steps) )-dione 2-(1-{[trans(2,4-dioxo-2,3,4,7-tet rahydro-1H-pyrrolo[3',2':5,6]pyrido[4 Colorless 5% ,3-d]pyrimidinyl)cyclohexyl]methyl solid (3steps) }azetidinyl)acetonitrile 1-(trans{[(2,2-dimethylcyclopropyl )amino]methyl}cyclohexyl)-1H-pyrrolo[ Colorless 35% 3',2':5,6]pyrido[4,3-d]pyrimidine-2,4 solid (3steps) (3H,7H)-dione 1-[trans({[(1-hydroxycyclohexyl)me thyl]amino}methyl)cyclohexyl]-1H-pyrr Colorless 23% olo[3',2':5,6]pyrido[4,3-d]pyrimidine solid (3steps) -2,4(3H,7H)-dione 2-({[trans(2,4-dioxo-2,3,4,7-tetra hydro-1H-pyrrolo[3',2':5,6]pyrido[4,3 Colorless 46% -d]pyrimidinyl)cyclohexyl]methyl}a solid (3steps) mino)acetonitrile 1-(trans{[4-(trifluoromethyl)piper idinyl]methyl}cyclohexyl)-1H-pyrro Colorless 70% lo[3',2':5,6]pyrido[4,3-d]pyrimidine- solid (3steps) 2,4(3H,7H)-dione 1-(trans{[3-hydroxy(trifluorome thyl)azetidinyl]methyl}cyclohexyl) Brown 55% -1H-pyrrolo[3',2':5,6]pyrido[4,3-d]py oil (3steps) rimidine-2,4(3H,7H)-dione 1-[trans({[(tetrahydrofuranyl)m ethyl]amino}methyl)cyclohexyl]-1H-pyr Colorless 72% rolo[3',2':5,6]pyrido[4,3-d]pyrimidin solid (3steps) e-2,4(3H,7H)-dione 1-(trans{[(2-methoxyethyl)amino]me thyl}cyclohexyl)-1H-pyrrolo[3',2':5,6 Colorless 19% ]pyrido[4,3-d]pyrimidine-2,4(3H,7H)-d solid (3steps) ione 1-[trans({[3,3,3-trifluorohydro xy(pyridinyl)propyl]amino}methy Colorless 61% 132 l)cyclohexyl]-1H-pyrrolo[3',2':5,6]py solid (3steps) rido[4,3-d]pyrimidine-2,4(3H,7H)-dion SYNTHETIC EXAMPLE 133 trans(2,4-Dioxo-2,3,4,7-tetrahydro-1H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidin yl)cyclohexanecarbaldehyde 1-[trans (Hydroxymethyl)cyclohexyl]-1H-pyrrolo[3',2':5,6]pyrido[4,3- d]pyrimidine-2,4(3H,7H)-dione (35.0 mg, 0.111 mmol) obtained in Synthetic Example 101 in a mixture of toluene (1 mL) and dimethyl sulfoxide (0.25 mL) was mixed with 2- iodoxybenzoic acid (37.4 mg, 0.133 mmol) and stirred at 50°C for 2 hours. The reaction mixture was allowed to cool to room temperature and stirred with saturated aqueous sodium thiosulfate and saturated aqueous sodium hydrogen carbonate at room temperature for 30 minutes. The precipitated solid was collected by filtration to give the title compound as a colorless solid (26.7 mg, yield 77%).

SYNTHETIC EXAMPLE 134 3-[trans(2,4-Dioxo-2,3,4,7-tetrahydro-1H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidin yl)cyclohexyl]propanenitrile 3-[trans(2,4-Dioxo{[2-(trimethylsilyl)ethoxy]methyl}-2,3,4,7-tetrahydro-1H- pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidinyl)cyclohexyl]acrylonitrile (16.2 mg, 0.0347 mmol) obtained in Reference Synthetic Example 170 in tetrahydrofuran (1.0 mL) was stirred with 5% palladium-carbon (10 mg) at room temperature for 1 day under a hydrogen atmosphere. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane (1.0 mL) and stirred with trifluoroacetic acid (0.4 mL) at room temperature for 5 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was stirred with methanol (0.7 mL), ethylenediamine (30 µL) and 1 M aqueous sodium hydroxide (30 µL) at room temperature for 1 day.

The reaction mixture was filtered, and the resulting solid was washed with water and methanol to give the title compound as a colorless solid (2.73 mg, yield 25% (three steps)).

SYNTHETIC EXAMPLE 135 2-Cyano-N-{[trans(2,4-dioxo-2,3,4,7-tetrahydro-1H-pyrrolo[3',2':5,6]pyrido[4,3- d]pyrimidinyl)cyclohexyl]methyl}-N-(2,2,2-trifluoroethyl)acetamide 1-(4-{[(2,2,2-Trifluoroethyl)amino]methyl}cyclohexyl){[2- (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidine-2,4(3H,7H)- dione (25.0 mg, 0.048 mmol) obtained in Reference Synthetic Example 169 in N,N- dimethylformamide (1 mL) was stirred with 2-cyanoacetic acid (10 mg, 0.071 mmol), O- (7-azabenzotriazolyl)-N,N,N’,N’-tetramethyluronium hexafluorophosphate (27 mg, 0.071 mmol) and N,N-diisopropylethylamine (16 µL, 0.095 mmol) at room temperature for 3 days. After addition of saturated aqueous sodium hydrogen carbonate, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform / methanol = 19/1 (v/v)) to give the compound as a yellow oil. The resulting yellow oil was dissolved in dichloromethane (1.0 mL) and stirred with trifluoroacetic acid (150 µL) at room temperature for 1 day. The reaction mixture was concentrated under reduced pressure, and the resulting residue was stirred with methanol (1 mL), ethylenediamine (50 µL) and 1 M aqueous sodium hydroxide (50 µL) at room temperature for 1 day. The precipitated solid was collected by filtration to give the title compound as a colorless 40 solid (2.70 mg, yield 14%(three steps)).

SYNTHETIC EXAMPLE 136 1-(trans{[Methyl(2,2,2-trifluoroethyl)amino]methyl}cyclohexyl)-1H- pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidine-2,4(3H,7H)-dione 1-(4-{[(2,2,2-Trifluoroethyl)amino]methyl}cyclohexyl){[2- 45 (trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidine-2,4(3H,7H)- dione (30 mg, 0.048 mmol) obtained in Reference Synthetic Example 169 in a mixture of methanol (1 mL) and acetic acid (100 µL) was stirred with formaldehyde solution (37%) (20 µL) and 2-picoline borane (15 mg, 0.14 mmol) at room temperature for 3 days. After addition of saturated aqueous ammonium chloride, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform / methanol = 19/1 (v/v)) to give the compound as a colorless solid. The resulting colorless solid was dissolved in dichloromethane (1 mL) and stirred with trifluoroacetic acid (150 µL) at room temperature for 1 day. The reaction mixture was concentrated under reduced pressure, and the resulting residue was stirred with methanol (1 mL), ethylenediamine (50 µL) and 1 M aqueous sodium hydroxide (50 µL) at room temperature for 1 day. The precipitated solid was collected by filtration to give the title compound as a colorless solid (24.95 mg, quantitative yield (three steps)).

SYNTHETIC EXAMPLE 137 2-(1-Cyclohexyl-2,4-dioxo-1H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidin-3(2H,4H,7H)- yl)acetonitrile 1-Cyclohexyl{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[3’,2’:5,6]pyrido[4,3- d]pyrimidine-2,4(3H,7H)-dione (20 mg, 0.048 mmol) obtained in Reference Synthetic Example 95 in N,N-dimethylformamide (1 mL) was mixed with potassium carbonate (10 mg, 0.072 mmol) and 2-chloroacetonitrile (5.0 µL, 0.072 mmol) and stirred at 80°C for 1 day. After addition of saturated aqueous ammonium chloride, the reaction mixture was extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane = 1/4 → 1/3 (v/v)) to give the compound as a yellow oil. The resulting yellow oil was dissolved in dichloromethane (1 mL) and stirred with trifluoroacetic acid (150 µL) at room temperature for 1 day. The reaction mixture was concentrated under reduced pressure, and the resulting residue was stirred with methanol (1 mL), ethylenediamine (50 µL) and 1 M aqueous sodium hydroxide (50 µL) at room temperature for 1 day. The precipitated solid was collected by filtration to give the title compound as a colorless solid (24.5 mg, yield 79%(three steps)).

SYNTHETIC EXAMPLES 138 TO 154 The reactions in Synthetic Example 137 were carried out in substantially the same manners except that iodomethane, 2,2,2-trifluoroethyl trifluoromethanesulfonate, 2-bromoethanol, 3-bromopropanol, 4-(2-chloroethyl)morpholine hydrochloride, chloro(methoxy)methane, 1-bromofluorobutane, 1-bromomethoxyethane, 2- bromopropanenitrile, (chloromethyl)(methyl)sulfane, bromocyclopentane, (bromomethyl)cyclopropane, 2-(bromomethyl)tetrahydrofuran, 3-(chloromethyl) methyloxetane, 2-chloro-N,N-dimethylacetamide, 2-chloro-N,N-dimethylethanamine hydrochloride or tert-butyl 4-bromopiperidinecarboxylate were used instead of 2- chloroacetonitrile to give the compounds of Synthetic Examples 138 to 154. The 40 names, morphologies and yields of the compounds synthesized are shown in Tables and 26.

TABLE 25 Ex Compound Name Morphology Yield 1-cyclohexylmethyl-1H-pyrrolo[3' Colorless 59% 138 ,2':5,6]pyrido[4,3-d]pyrimidine-2,4 solid (3steps) (3H,7H)-dione 1-cyclohexyl(2,2,2-trifluoroethy Colorless 49% l)-1H-pyrrolo[3',2':5,6]pyrido[4,3- solid (3steps) d]pyrimidine-2,4(3H,7H)-dione 1-cyclohexyl(2-hydroxyethyl)-1H- Colorless 61% 140 pyrrolo[3',2':5,6]pyrido[4,3-d]pyri solid (3steps) midine-2,4(3H,7H)-dione 1-cyclohexyl(3-hydroxypropyl)-1H Colorless 31% 141 -pyrrolo[3',2':5,6]pyrido[4,3-d]pyr solid (3steps) imidine-2,4(3H,7H)-dione 1-cyclohexyl(2-morpholinoethyl)- Colorless 68% 142 1H-pyrrolo[3',2':5,6]pyrido[4,3-d]p solid (3steps) yrimidine-2,4(3H,7H)-dione 1-cyclohexyl(methoxymethyl)-1H-p Colorless 49% yrrolo[3',2':5,6]pyrido[4,3-d]pyrim solid (3steps) idine-2,4(3H,7H)-dione 1-cyclohexyl(4-fluorobutyl)-1H-p Colorless 55% 144 yrrolo[3',2':5,6]pyrido[4,3-d]pyrim solid (3steps) idine-2,4(3H,7H)-dione 1-cyclohexyl(2-methoxyethyl)-1H- Colorless 60% pyrrolo[3',2':5,6]pyrido[4,3-d]pyri solid (3steps) midine-2,4(3H,7H)-dione 2-(1-cyclohexyl-2,4-dioxo-1H-pyrrol Colorless 72% 146 o[3',2':5,6]pyrido[4,3-d]pyrimidin- solid (3steps) 3(2H,4H,7H)-yl)propanenitrile 1-cyclohexyl[(methylthio)methyl] Colorless 80% 147 -1H-pyrrolo[3',2':5,6]pyrido[4,3-d] solid (3steps) pyrimidine-2,4(3H,7H)-dione TABLE 26 Ex Compound Name Morphology Yield 1-cyclohexylcyclopentyl-1H-pyrro Colorless 55% 148 lo[3',2':5,6]pyrido[4,3-d]pyrimidin solid (3steps) e-2,4(3H,7H)-dione 1-cyclohexyl(cyclopropylmethyl)- Colorless 99% 1H-pyrrolo[3',2':5,6]pyrido[4,3-d]p solid (3steps) yrimidine-2,4(3H,7H)-dione 1-cyclohexyl[(tetrahydrofuran yl)methyl]-1H-pyrrolo[3',2':5,6]pyr Colorless 83% ido[4,3-d]pyrimidine-2,4(3H,7H)-dio solid (3steps) 1-cyclohexyl[3-hydroxy(hydrox ymethyl)methylpropyl]-1H-pyrrolo Colorless 56% [3',2':5,6]pyrido[4,3-d]pyrimidine- solid (3steps) 2,4(3H,7H)-dione 2-(1-cyclohexyl-2,4-dioxo-1H-pyrrol o[3',2':5,6]pyrido[4,3-d]pyrimidin- Colorless 64% 3(2H,4H,7H)-yl)-N,N-dimethylacetami solid (3steps) 1-cyclohexyl[2-(dimethylamino)et Colorless 30% 153 hyl]-1H-pyrrolo[3',2':5,6]pyrido[4, solid (3steps) 3-d]pyrimidine-2,4(3H,7H)-dione 1-cyclohexyl(piperidinyl)-1H- Colorless 15% 154 pyrrolo[3',2':5,6]pyrido[4,3-d]pyri solid (3steps) midine-2,4(3H,7H)-dione SYNTHETIC EXAMPLE 155 N-{[trans(2,4-Dioxo-2,3,4,7-tetrahydro-1H-pyrrolo[3',2':5,6]pyrido[4,3-d]pyrimidin yl)cyclohexyl]methyl}-3,3,3-trifluoro-N-(2,2,2-trifluoroethyl)propanamide The reactions in Synthetic Example 135 were carried out in substantially the same manners except that 3,3,3-trifluoropropanoic acid was used instead of 2- cyanoacetic acid to give the title compound as a colorless solid (1.95 mg, yield 8% (three steps)).

The structural formulae of the compounds obtained the Reference Synthetic b b b Examples and Synthetic Examples are shown below in Tables 27 to 44. The physical property data on the compounds obtained the Reference Synthetic Examples and Synthetic Examples are shown below in Tables 45 to 77.

TABLE 27 Rf Structure Rf Structure Rf Structure N Ph 1 2 3 N Ph HN HN racemate racemate 4 N 5 6 TIPS 7 8 9 HN O N HN 11 12 HO H N HN N 13 14 15 Br Br 16 17 18 N N H Br HN O HN 19 20 Br 21 SEM SEM OH HN O N 22 23 24 racemate racemate SEM SEM TABLE 28 Rf Structure Rf Structure Rf Structure 26 27 S TIPS N HN O HN HO C 28 29 2 30 N N N O Cl O O HN N N 31 32 33 N N SEM N Ph N Ph NH O HN N N 34 35 36 racemate SEM racemate racemate N Ph N N Ph 37 38 39 racemate racemate racemate N Ph N Ph OH HN O N 40 41 42 SEM SEM racemate racemate Br Cl 43 44 45 H SEM O Cl O HN N 46 47 48 SEM N N SEM SEM TABLE 29 Rf Structure Rf Structure Rf Structure O Cl N Ph N Ph O HN N Br Br 49 50 51 racemate racemate O Cl N Ph N Ph O HN N Cl Cl 52 53 54 SEM SEM racemate racemate O Cl OH Cl O Cl 55 56 57 N N N racemate SEM N Ph N Ph Br N Ph O HN N 58 59 60 SEM SEM racemate racemate racemate N S CN O O O O CN O 61 62 63 O O O SEM racemate racemate SEM racemate N N N N CF O O O CF 64 65 66 racemate racemate SEM racemate N S CF N CF 3 67 68 69 N N N racemate SEM SEM racemate racemate TABLE 30 Rf Structure Rf Structure Rf Structure N O H 70 71 72 racemate racemate H N N 73 74 N 75 racem ate SEM racemate N CF N 76 77 78 N N N racemate racemate racemate N N N N N C N N CF CN 79 80 81 N N N SEM SEM racemate racemate SEM racem ate 82 83 84 SEM N SEM racemate racemate racemate 85 86a 86b N N N SEM SEM racemate more polar fraction less polar fraction O Cl O Cl N O HN 87 88 89 SEM SEM TABLE 31 Rf Structure Rf Structure Rf Structure O NH HN N HN N HN N CN 90 91 92 HN N HN N HN N CF 93 94 95 O Cl O HN N 96 97 98 SEM SEM N CF 99 100 101 N CN N CN 102 103 104 SEM N N HN HN 105 106 107 SEM SEM O NH HN N HN N HN N 108 109 110 TABLE 32 Rf Structure Rf Structure Rf Structure O N O N HN N N HN N CN HN N CF 111 112 113 SEM SEM N CF O N N HN N HN N HN N 114 115 116 HN HN 117 118 119 racemate SEM racemate racemate HN N 120 121 122 racemate racemate O HN 123 124 125 126 127 128 NO2 CO Et CF 2 129 130 131 N N N TABLE 33 Rf Structure Rf Structure Rf Structure N Cl N N CF N F 3 132 133 134 SEM SEM N N F 135 136 137 N N N SEM SEM N Br 138 139 140 N N F N O N 141 142 143 O O O SEM SEM TABLE 34 Rf Structure Rf Structure Rf Structure N H B o c S O N O N HN N HN N 145 146 147 SEM SEM N HN N HN N HN N 148 149 150 racemate O N C N O N C F HN N HN N HN N 151 152 153 N N N SEM SEM O N C N N CF HN N HN N HN N 154 155 156 racemate SEM N HN N OH H 157 158 O a N 2 cis/trans mixture 160 161 b OH N H N Boc Boc 162 163 164 CN CN O OH HN HN N O HN 165 166 167 CN O O N CF HN N HN N HN N 168 169 170 E/Z mixture SEM N TABLE 35 Rf Structure Rf Structure Rf Structure O HN HN N O HN 171 172 173 H N H N HN N 174 175 176 177 N 178 179 racemate TABLE 36 Ex Structure Ex Structure Ex Structure O N O N 1 2 3 N N N N N N H H H N Ph 4 5 6a racemate racemate racemate N CN 6b 7 8 racemate N H H racemate racemate N N N N CF N S CF O O O O 9 10 11 racemate racemate N racemate N N N 12 O 13 14 racemate N N N NH N HN N O N O N CN 16 17 racemate racemate N N N 18 19 20 N N N H H TABLE 37 Ex Structure Ex Structure Ex Structure Br Cl 21 22 23 N racemate racemate H N racemate N Br N N S CN 24 25 O O 26 O O racemate N N racemate racemate N O N N N N CF 27 28 29 O O O O O O N racemate N racemate H racemate N CF N 31 32 O CF O O O O O F racemate racemate H racemate H N S C F N 33 O O 34 35 N racemate H N racemate N racemate 36 37 38 racemate N racemate H N racemate N C F 39 40 41 N racemate N racem ate racemate TABLE 38 Ex Structure Ex Structure Ex Structure N CN 42 43 44 N racem ate N racemate H N racemate 45 46 47 racemate N racemate H H racemate HN N 48a 48b 49 less polar fraction N more polar fraction HN N CN HN N HN N CF 50 51 52 HN N 53 54 55 N CN N CF N CN 56 57 58 HN N N HN N HN N 59 60 61 TABLE 39 Ex Structure Ex Structure Ex Structure O N N HN N CN HN N C F HN N 62 63 64 O N O HN N HN N HN N 65 66 67 racemate O NH HN N N 68 69 70 CF NO2 CO Et N N N 71 72 73 O O O N N N N N N N N CF N F N Cl 3 74 75 76 Cl S N N F 77 78 79 O O O 80 81 82 TABLE 40 Ex Structure Ex Structure Ex Structure 83 84 85 86 87 TABLE 41 Ex Structure Ex Structure Ex Structure NH S HN N HN N HN N 88 89 90 HN N HN N HN N 91 92 93 racemate O N O N HN N HN N H N N 94 95 96 O N N HN N HN N HN N 97 98 99 N racemate O OH HN N HN N HN N 100 101 102 HN N HN N HN N 103 104 105 O OH E/Z mixture N N N H N H OH O HN N 106 107 108 O H O TABLE 42 Ex Structure Ex Structure Ex Structure H N N O N O N HN N HN N HN N 109 110 111 HN N HN N HN N 112 113 114 HN N HN N HN N 115 116 117 HN N HN N HN N 118 119 120 O N N HN N HN N HN N 121 122 123 HN N HN N 124 125 HN N 126 racemate N O N HN N HN N HN N 127 128 129 TABLE 43 Ex Structure Ex Structure Ex Structure H O N N HN N HN HO CF HN N 130 131 132 racemate H N racemate HN N HN N O HN N 133 134 135 N N N N HN N 136 137 138 N N HO N N 139 140 141 O N N 142 143 144 N S N N 145 146 147 racemate TABLE 44 Ex Structure Ex Structure Ex Structure N N N N 148 149 150 racemate N N N N HO N N 151 152 153 O O O N N N HN O F HN N O 154 155 O F F TABLE 45 Rf Data H-NMR (CD OD) δ : 3.31 (s, 3H), 3.76 (s, 3H), 7.28 (d, J = 5.36 Hz, 1H), 8.18 (d, J = 4.76 Hz, 1H), 8.57 (s, 1H).

LC/MS:condition 1, retention time = 0.54 min LC/MS(ESI ) m/z; 167 [M+H] H-NMR (CDCl ) δ : 0.98 (d, J = 6.5 Hz, 3H), 1.56-1.83 (m, 3H), 2.20-2.35 (m, 1H), 2.61-2.85 (m, 1H), 3.31 (d, J = 10.9 Hz, 1H), 3.53 (d, J = 14.9 Hz, 1H), 3.67 (s, 3H), 4.02 (dd, J = 13.0, 5.4, 2 1H), 4.13-4.26 (m, 2H), 7.47 (d, J = 2.4 Hz, 2H), 7.55 (d, J =2.38 Hz, 3H), 12.4 (bs, 1H).

LC/MS: condition 1, retention time = 0.51 min LC/MS(ESI ) m/z; 263 [M+H] H-NMR (CDCl ) δ : 0.92 (d, 3H), 1.41-1.53 (m, 3H), 1.90-2.18 (m, 2H), 2.65-2.89 (m, 3H), 3.46 (s, 2H), 7.18-7.40 (m, 5H).

LC/MS: condition 1, retention time = 0.47 min LC/MS(ESI ) m/z; 205 [M+H] H-NMR (CDCl ) δ : 6.55 (d, J = 3.3 Hz, 1H), 7.06 (dd, J = 8.0, 6.3Hz, 1H), 7.43 (d, J = 3.3 Hz, 1H), 7.70 (d, J = 8.0 Hz, 1H), 8.26 (d, 4 J = 6.3 Hz, 1H).

LC/MS: condition 1, retention time = 0.64 min LC/MS(ESI ) m/z; 135.0 [M+H] H-NMR (CDCl ) δ : 6.63 (d, J = 3.6 Hz, 1H), 7.14 (d, J = 5.2 Hz, 1H), 7.39 (d, J = 3.6 Hz, 1H), 8.22 (d, J = 5.2 Hz, 1H), 10.4 (br s, 1H).

LC/MS: condition 1, retention time = 3.16 min LC/MS(ESI ) m/z; 153, 155 [M+H] H-NMR (CDCl ) δ : 1.11 (d, J = 7.5 Hz, 18H), 1.84 (septet, J = 7.5 Hz, 3H), 6.65 (d, J = 3.6 Hz, 1H), 7.06 (d, J = 5.2 Hz, 1H), 7.33 6 (d, J = 3.6 Hz, 1H), 7.75 (d, J = 5.2 Hz, 1H).

LC/MS: condition 1, retention time = 6.91 min LC/MS(ESI ) m/z; 309, 311 [M+H] H-NMR (DMSO-d ) δ : 6.73 (dd, J = 3.6, 2.1Hz, 1H), 7.75 (br t, J = 3.0 Hz, 1H), 8.68 (s, 1H), 10.4 (s, 1H), 12.5 (bs, 1H). 7 LC/MS: condition 1, retention time = 3.19 min LC/MS(ESI ) m/z; 181, 183 [M+H] LC/MS(ESI ) m/z; 179, 181 [M-H] H-NMR (CDCl ) δ : 1.29-1.56 (m, 4H), 1.60-1.75 (m, 2H), 1.78-1.92 (m, 2H), 2.07-2.20 (m, 2H), 3.94-4.06 (m, 1H), 6.59 (d, J = 3.6 Hz, 1H), 7.10 (d, J = 3.6 Hz, 1H), 8.20 (s, 1H), 9.62 (br d, J = 7.6 Hz, 1H), 9.80 (s, 1H), 11.0 (br s, 1H).

LC/MS: condition 1, retention time = 3.02 min LC/MS(ESI ) m/z; 244 [M+H] H-NMR (CDCl ) δ : -0.05 (s, 9H), 0.91 (t, J = 8.5 Hz, 2H), 1.25-1.75 (m, 6H), 1.75-1.90 (m, 2H), 2.07-2.20 (m, 2H), 3.54 (t, J = 8.5 Hz, 2H), 3.90-4.05 (m, 1H), 5.61 (s, 2H), 6.60 (d, J = 3.8 Hz, 1H), 9 7.09 (d, J = 3.8 Hz, 1H), 8.18 (s, 1H), 9.58 (br d, J = 7.7 Hz, 1H), 9.80 (s, 1H).

LC/MS: condition 1, retention time = 5.22 min LC/MS(ESI ) m/z; 374 [M+H] TABLE 46 Rf Data H-NMR (CDCl ) δ: -0.06 (s, 9H), 0.90-1.00 (m, 2H), 1.10-1.80 (m, 6H), 1.80-1.95 (m, 2H), 1.95-2.10 (m, 2H), 3.50-3.60 (m, 2H), 3.90-4.10 (m, 1H), 4.76 (s, 2H), 4.96 (s, 2H), 5.62 (s, 2H), 6.43 (d, J = 3.6 Hz, 1H), 7.20 (d, J = 3.6 Hz, 1H), 7.82 (s, 1H).

LC/MS: condition 1, retention time = 3.86 min LC/MS(ESI ) m/z; 388 [M+H] H-NMR (CDCl ) δ : -0.06 (s, 9H), 0.90 (t, J = 8.3 Hz, 2H), 1.37-1.54 (m, 6H), 1.74-1.92 (m, 2H), 2.02-2.24 (m, 2H), 3.54 (t, J= 8.0 Hz, 2H), 12 3.83-4.04 (m, 3H), 5.58, (s, 2H), 6.52 (d, J = 3.9 Hz,1H), 6.74-6.94 (m, 1H), 7.08 (d, J = 3.3 Hz, 1H), 7.79(s, 1H).

LC/MS: condition 1, retention time = 3.02 min LC/MS(ESI ) m/z; 375 [M+H] H-NMR (CDCl ) δ : -0.05 (s, 9H), 0.92, (t, J = 8.3 Hz, 2H), 1.23-1.50 (m, 3H), 1.57-1.84 (m, 2H), 1.84-2.02 (m, 3H), 2.63-2.67 (m, 2H), 3.54 (t, J = 8.0 Hz, 2H), 4.00-4.23 (m, 1H), 4.36 (d, 13 J = 2.1 Hz, 2H), 5.20 (s, 1H), 5.65 (s, 2H), 6.49 (d, J = 3.6 Hz, 1H), 7.30 (d, J = 3.9 Hz 1H), 7.97 (s, 1H).

LC/MS: condition 1, retention time = 4.79 min LC/MS(ESI ) m/z; 401 [M+H] LC/MS: condition 1, retention time = 3.46 min LC/MS(ESI ) m/z; 385 [M+H] H-NMR (CDCl ) δ: 3.06 (t, J = 8.1 Hz, 2H), 3.61 (t, J = 8.1 Hz, 2H), 4.48 (br s, 1H), 6.50 (dd, J = 5.4, 6.9 Hz, 1H), 7.24 (d, J = 6.9 Hz, 1H), 7.81 (d, J = 5.4 Hz, 1H).

LC/MS: condition 1, retention time = 0.50 min LC/MS(ESI ) m/z; 121 [M+H] H-NMR (CDCl ) δ: 3.07 (t, J = 8.4 Hz, 2H), 3.65 (t, J = 8.1 Hz, 2H), 4.50 (br s, 1H), 7.32 (s, 1H), 7.85 (s, 1H).

LC/MS: condition 1, retention time = 0.52 min LC/MS(ESI ) m/z; 199, 201 [M+H] H-NMR (CDCl ) δ: 6.40-6.50 (m, 1H), 7.30-7.40 (m, 1H), 8.07 (d, J = 2.1 Hz, 1H), 8.35 (d, J = 1.5 Hz, 1H), 9.50 (br s, 1H).

LC/MS: condition 1, retention time = 3.52 min LC/MS(ESI ) m/z; 197, 199 [M+H] LC/MS: condition 1, retention time = 1.36 min LC/MS(ESI ) m/z; 213, 215 [M+H] H-NMR (CDCl ) δ: -0.06 (s, 9H), 0.90 (t, J = 8.1 Hz, 2H), 3.52 (t, J = 7.8 Hz, 2H), 5.63 (s, 2H), 6.60 (d, J = 3.6 Hz, 1H), 7.38 19 (d, J = 3.6 Hz, 1H), 8.41 (s, 1H).

LC/MS: condition 1, retention time = 5.54 min LC/MS(ESI ) m/z; 361, 363, 365 [M+H] H-NMR (CDCl ) δ :-0.06 (s, 9H), 0.90 (t, J = 8.1 Hz, 2H), 1.30-1.70 (m, 6H), 1.80-1.90 (m, 2H), 2.10-2.20 (m, 2H), 3.53 (t, J = 8.1 Hz, 2H), 3.90-4.00 (m, 1H), 4.97 (d, J = 8.4 Hz, 1H), 5.58 (s, 2H), 6.51 (d, J = 3.6 Hz, 1H), 7.12 (d, J = 3.9 Hz, 1H), 8.11 (s, 1H).

LC/MS: condition 1, retention time = 5.42 min LC/MS(ESI ) m/z; 424, 426 [M+H] TABLE 47 Rf Data LC/MS: condition 1, retention time = 5.01 min LC/MS(ESI ) m/z; 388 [M+H] LC/MS: condition 1, retention time = 4.01 min LC/MS(ESI ) m/z; 402 [M+H] H-NMR (CDCl ) δ : -0.06 (s, 9H), 0.93 (t, J = 8.1 Hz, 2H), 1.50-1.95 (m, 6H), 2.00-2.15 (m, 2H), 2.20-2.30 (m, 2H), 3.56 (t, J = 8.1 Hz, 2H), 4.85-5.00 (m, 1H), 5.80 (s, 2H), 6.43 (d, J = 8.1 Hz, 1H), 24 6.81 (d, J = 3.6 Hz, 1H), 7.43 (d, J = 3.9 Hz, 1H), 7.77 (d, J = 8.1 Hz, 1H), 9.41 (s, 1H).

LC/MS: condition 1, retention time = 4.64 min LC/MS(ESI ) m/z; 398 [M+H] LC/MS: condition 1, retention time = 5.46 min LC/MS(ESI ) m/z; 387, 389 [M+H] H-NMR (CDCl ) δ : 1.30-1.60 (m, 4H), 1.60-1.80 (m, 2H), 1.80-1.95 (m, 2H), 2.10-2.25 (m, 2H), 3.07 (s, 3H), 3.95-4.10 (m, 1H), 6.61 (d, J = 3.3 Hz, 1H), 7.15-7.25 (m, 2H), 8.54 (s, 1H), 11.82 (br s, 1H).

LC/MS: condition 1, retention time = 3.31 min LC/MS(ESI ) m/z; 294 [M+H] LC/MS: condition 1, retention time = 4.87 min LC/MS(ESI ) m/z; 434 [M+H] LC/MS: condition 1, retention time = 4.26 min 29 LC/MS(ESI+) m/z; 390 [M+1]+ LC/MS(ESI-) m/z; 388 [M-1]- H-NMR (CDCl ) δ : -0.05 (s, 9H), 0.91 (t, J = 8.1 Hz, 2H), 1.35-1.45 (m, 5H), 1.60-1.70 (m, 1H), 1.75-1.90 (m, 2H), 2.05-2.20 (m, 2H), 3.54 (t, J = 7.8 Hz, 2H), 3.90-4.05 (m, 1H), 5.58 (s, 2H), 5.55-5.70 (m, 2H), 6.59 (d, J = 3.6 Hz, 1H), 7.08 (d, J = 3.9 Hz, 1H), 8.29 (s, 1H), 9.32 (d, J = 7.5 Hz, 1H).

LC/MS: condition 1, retention time = 4.02 min LC/MS(ESI ) m/z; 389 [M+H] LC/MS: condition 1, retention time = 4.97 min LC/MS(ESI ) m/z; 417 [M+H] H-NMR (CDCl ) δ : -0.06 (s, 9H), 0.93 (t, J = 8.1 Hz, 2H), 1.50-2.00 (m, 6H), 2.00-2.15 (m, 2H), 2.20-2.40 (m, 2H), 3.56 (t, J = 8.1 Hz, 2H), 4.70-4.85 (m, 1H), 5.79 (s, 2H), 6.77 (d, J = 4.2 Hz, 1H), 7.51 (d, J = 3.9 Hz, 1H), 8.50 (s, 1H), 9.32 (s, 1H).

LC/MS: condition 1, retention time = 4.42 min LC/MS(ESI ) m/z; 399 [M+H] H-NMR (CDCl ) δ : -0.06 (s, 9H), 0.85-1.00(m, 2H), 2.76 (s, 3H), 3.50-3.60 (m, 2H), 5.68 (s, 2H), 6.74 (d, J = 3.6 Hz, 1H), 7.44 33 (s, J = 3.6 Hz, 1H), 8.66 (s, 1H).

LC/MS: condition 1, retention time = 4.87 min LC/MS(ESI ) m/z; 325, 327 [M+H] TABLE 48 Rf Data H-NMR (CDCl ) δ: -0.06 (s, 9H), 0.90 (t, J = 8.1 Hz, 2H), 0.98 (d, J = 6.6 Hz, 3H), 1.60-1.85 (m, 2H), 1.90-2.00 (m, 1H), 2.20-2.30 (m, 1H), 2.25-2.35 (m, 1H), 2.67 (s, 3H), 2.70-2.90 (m, 2H), 3.45-3.60 (m, 4H), 4.30-4.40 (m, 1H), 5.57 (s, 2H), 6.58 (d, J = 3.6 Hz, 1H), 7.00 (d, J = 3.9 Hz, 1H), 7.10-7.40 (m, 5H), 8.66 (s, 1H), 10.70 (d, J = 9.9 Hz, 1H).

H-NMR (CDCl ) δ: -0.08 (s, 9H), 0.86 (d, J = 6.9 Hz, 3H), 0.91 (t, J = 8.1 Hz, 2H), 1.70-2.00 (m, 2H), 2.40-2.60 (m, 2H), 2.75-2.90 (m, 2H), 2.95-3.05 (m, 1H), 3.50-3.65 (m, 4H), 5.35-5.45 (m, 1H), 5.78 (dd, J = 10.5, 15.0 Hz, 2H), 6.39 (d, J = 8.1 Hz, 1H), 6.81 (d, J = 3.9 Hz, 1H), 7.25-7.40 (m, 5H), 7.41 (d, J = 3.6 Hz, 1H), 8.54 (br s, 1H), 9.41 (s, 1H).

LC/MS: condition 1, retention time = 3.59 min LC/MS(ESI ) m/z; 503 [M+H] LC/MS: condition 1, retention time = 3.06 min LC/MS(ESI ) m/z; 413 [M+H] H-NMR (CDCl ) δ: -0.06 (s, 9H), 0.93 (t, J = 8.1 Hz, 2H), 1.02 (d, J = 7.5 Hz, 3H), 1.14 (d, J = 6.6 Hz, 6H), 1.80-1.90 (m, 1H), 2.15-2.45 (m, 2H), 2.65-2.80 (m, 1H), 2.87 (d, J = 6.6 Hz, 2H), 3.15-3.35 (m, 1H), 3.56 (t, J = 8.1 Hz, 2H), 3.55-3.75 (m, 2H), 3.85-3.95 (m, 1H), 5.35-5.45 (m, 1H), 5.80 (s, 2H), 6.40 (d, J = 7.8 Hz, 1H), 6.75 (d, J = 3.6 Hz, 1H), 7.46 (d, J = 3.9 Hz, 1H), 7.60 (d, J = 8.1 Hz, 1H), 9.42 (s, 1H).

LC/MS: condition 1, retention time = 4.52 min LC/MS(ESI ) m/z; 533 [M+H] LC/MS(ESI ) m/z; 577 [M+HCOO] LC/MS: condition 1, retention time = 0.54 min LC/MS(ESI ) m/z; 349 [M+H] H-NMR (CDCl ) δ : -0.06 (s, 9H), 0.87-0.95 (m, 2H), 0.98 (d, J = 6.9 Hz, 3H), 1.59-1.80 (m, 2H), 1.87-2.04 (m, 1H), 2.14-2.24 (m, 1H), 2.38-2.41 (m, 1H), 2.85-2.89 (m, 2H), 3.47-3.62 (m, 4H), 4.28-4.39 (m, 1H), 5.59 (s, 2H), 6.59 (d, J = 3.6 Hz, 1H), 7.04 (d, J = 3.9 Hz, 1H), 7.17-7.39 (m, 5H), 8.20 (s, 1H), 9.87 (s, 1H), .0(d, J = 9.5 Hz, 1H).

LC/MS: condition 1, retention time = 3.57 min LC/MS(ESI ) m/z; 479 [M+H] H-NMR (CDCl ) δ : -0.07 (s, 9H), 0.86-0.92 (m, 2H), 1.01 (d, J = 6.6 Hz, 3H), 1.43-1.96 (m, 3H), 2.07-2.14 (m, 1H), 2.25-2.28 (m, 1H), 2.78-2.93 (m, 2H), 3.46-3.55 (m, 4H), 4.20-4.31 (m, 1H), 4.77 (dd, J = 20.8, 12.2 Hz, 2H), 5.57 (s, 2H), 5.95 (d, J = 9.8 Hz, 1H), 6.51 (d, J = 3.6 Hz, 1H), 7.07 (d, J = 3.6 Hz, 1H), 7.18-7.29 (m, 5H), 7.87 (s, 1H).

LC/MS: condition 1, retention time = 3.04 min LC/MS(ESI ) m/z; 481 [M+H] LC/MS: condition 1, retention time = 2.91 min LC/MS(ESI ) m/z; 363 [M+H-SEM] H-NMR (DMSO-d ) δ: 8.30 (br s, 1H), 8.44 (s, 1H), 8.49 (s, 1H).

LC/MS: condition 1, retention time = 0.89 min LC/MS(ESI ) m/z; 198, 200 [M+H] LC/MS(ESI ) m/z; 196, 198 [M-H] ABLE 49 Rf Data LC/MS: condition 1, retention time = 0.54 min LC/MS(ESI ) m/z; 214, 216 [M+H] H-NMR (DMSO-d ) δ : 8.50 (s, 1H), 8.56 (s, 1H), 8.57 (d, J = 1.8 Hz, 1H).

LC/MS: condition 1, retention time = 2.74 min LC/MS(ESI ) m/z; 232, 234, 236 [M+H] LC/MS(ESI ) m/z; 230, 232, 234 [M-H] H-NMR (CDCl ) δ : -0.04 (s, 9H), 0.94 (t, J = 8.4 Hz, 2H), 2.79 (s, 3H), 3.62 (t, J = 8.4 Hz, 2H), 5.69 (s, 2H), 8.30 (s, 1H), 8.73 46 (s, 1H).

LC/MS: condition 1, retention time = 4.31 min LC/MS(ESI ) m/z; 326, 328 [M+H] H-NMR (CDCl ) δ : -0.03 (s, 9H), 0.93 (t, J = 8.4 Hz, 2H), 1.22-1.78 (m, 6H), 1.78-1.90 (m, 2H), 2.03-2.18 (m, 2H), 2.63 (s, 3H), 3.61 (t, J = 8.4 Hz, 2H), 4.87-5.03 (m, 1H), 5.58 (s, 2H), 7.88 (s, 1H), 8.69 (s, 1H), 10.10 (br s, 1H).

LC/MS: condition 1, retention time = 5.19 min LC/MS(ESI ) m/z; 389 [M+H] H-NMR (CDCl ) δ : -0.04 (s, 9H), 0.95 (t, J = 8.4 Hz, 2H), 1.20-1.38 (m, 1H), 1.58-2.24 (m, 9H), 3.65 (t, J = 8.4 Hz, 2H), 5.77 (s, 2H), 6.46 (d, J = 8.0 Hz, 1H), 6.40-6.55 (m, 1H), 7.81 (d, J = 8.0 Hz, 1H), 8.16 (s, 1H), 9.47 (s, 1H).

LC/MS: condition 1, retention time = 4.66 min LC/MS(ESI ) m/z; 399 [M+H] TABLE 50 Rf Data H-NMR (CDCl ) δ : -0.04 (s, 9H), 0.92 (t, J = 8.4 Hz, 2H), 2.74 (s, 3H), 3.53 (t, J = 8.7 Hz, 2H), 5.64 (s, 2H), 7.48 (s, 1H), 49 8.54 (s, 1H).

LC/MS: condition 1, retention time = 5.19 min LC/MS(ESI ) m/z; 403, 405 [M+H] H-NMR (CDCl ) δ : -0.07 (s, 9H), 0.72 (d, J = 6.3 Hz, 3H), 0.96 (t, J = 8.1 Hz, 2H), 1.45-1.60 (m, 1H), 1.70-1.90 (m, 2H), 2.05-2.18 (m, 1H), 2.31-2.42 (m, 1H), 2.71 (s, 3H), 2.88-3.00 (m, 1H), 3.10-3.22 (m, 1H), 3.51-3.69 (m, 4H), 4.60-4.80 (m, 1H), 5.61 (dd, J = 10.8, 16.2 Hz, 2H), 7.21-7.43 (m, 6H), 8.65 (s, 1H).

LC/MS: condition 1, retention time = 3.86 min LC/MS(ESI ) m/z; 571, 573 [M+H] H-NMR (CDCl ) δ : -0.08 (s, 9H), 0.20 (d, J = 6.9 Hz, 3H), 0.90 (t, J = 8.7 Hz, 2H), 1.40-1.52 (m, 1H), 1.62-1.72 (m, 1H), 1.82-2.00 (m, 1H), 2.05-2.20 (m, 1H), 2.70-2.82 (m, 1H), 3.02-3.17 (m, 1H), 3.50-3.60 (m, 4H), 3.60-3.71 (m, 1H), 51 5.40-5.50 (m, 1H), 5.74 (dd, J = 13.8, 10.5 Hz, 2H), 6.44 (d, J = 7.8 Hz, 1H), 7.20-7.45 (m, 5H), 7.47 (s, 1H), 9.34 (s, 1H), 9.49 (d, J = 7.8 Hz, 1H).

LC/MS: condition 1, retention time = 4.89 min LC/MS(ESI ) m/z; 581, 583 [M+H] H-NMR (CDCl ) δ : -0.05 (s, 9H), 0.91 (t, J = 8.4 Hz, 2H), 2.74 (s, 3H), 3.52 (t, J = 8.1 Hz, 2H), 5.63 (s, 2H), 7.40 (s, 1H), 52 8.54 (s, 1H).

LC/MS: condition 1, retention time = 5.00 min LC/MS(ESI ) m/z; 359, 361 [M+H] LC/MS: condition 1, retention time = 3.67 min LC/MS(ESI ) m/z; 527, 529 [M+H] H-NMR (CDCl ) δ : -0.10 (s, 9H), 0.27 (d, J = 6.9 Hz, 3H), 0.90 (t, J = 8.4 Hz, 2H), 1.41-1.56 (m, 1H), 1.60-1.80 (m, 1H), 1.86-2.03 (m, 1H), 2.06-2.20 (m, 1H), 2.68-2.80 (m, 1H), 3.05-3.20 (m, 1H), 3.50-3.70 (m, 5H), 5.35-5.42 (m, 1H), 5.74 (s, 2H), 6.44 (d, J = 8.1 Hz, 1H), 7.22-7.48 (m, 6H), 9.34 (s, 1H), 9.45 (d, J = 8.1 Hz, 1H).

LC/MS: condition 1, retention time = 4.60 min LC/MS(ESI ) m/z; 537, 539 [M+H] LC/MS: condition 1, retention time = 4.79 min LC/MS(ESI ) m/z; 311, 313 [M+H] H-NMR (CDCl ) δ : -0.07 (s, 9H), 0.90 (t, J = 8.4 Hz, 2H), 1.00 (t, J = 7.2 Hz, 3H), 1.91 (quint, J = 7.2 Hz, 2H), 3.53 (t, J = 8.4 Hz, 2H), 5.10-5.20 (m, 1H), 5.65 (s, 2H), 6.60 (d, J = 3.6 Hz, 1H), 7.36 (d, J = 3.6 Hz, 1H), 8.45 (s, 1H).

LC/MS: condition 1, retention time = 4.81 min LC/MS(ESI ) m/z; 341, 343 [M+H] LC/MS: condition 1, retention time = 5.21 min LC/MS(ESI ) m/z; 339, 341 [M+H] LC/MS: condition 1, retention time = 3.71 min LC/MS(ESI ) m/z; 507 [M+H] TABLE 51 Rf Data H-NMR (CDCl ) δ: -0.10 (s, 9H), 0.85 (d, J = 7.2 Hz, 3H), 0.90 (t, J = 9.0 Hz, 2H), 1.70-1.85 (m, 1H), 1.85-2.00 (m, 1H), 2.19 (s, 3H), 2.35-2.58 (m, 2H), 2.75-2.90 (m, 2H), 3.00-3.12 (m, 1H), 3.50-3.70 (m, 4H), 5.33-5.41 (m, 1H), 5.77 (dd, J = 9.9, 15.0 Hz, 2H), 6.79 (d, J = 3.6 Hz, 1H), 7.20-7.40 (m, 6H), 8.51 (br s, 1H), 9.45 (s, 1H).

LC/MS: condition 1, retention time = 3.74 min LC/MS(ESI ) m/z; 517 [M+H] LC/MS: condition 1, retention time = 4.24 min LC/MS(ESI ) m/z; 581, 583 [M+H] H-NMR (CDCl ) δ : -0.05 (s, 9H), 0.85-0.95 (m, 2H), 0.99 (d, J = 7.5 Hz, 3H), 1.85-1.95 (m, 1H), 2.25-2.35 (m, 1H), 2.65-2.75 (m, 1H), 3.35-3.45 (m, 1H), 3.58 (t, J = 8.1 Hz, 2H), 3.65-3.85 (m, 2H), 3.90-4.00 (m, 1H), 5.40-5.50 (m, 1H), 5.80 (s, 2H), 6.36 61 (d, J = 8.1 Hz, 1H), 6.75 (d, J = 3.6 Hz, 1H), 7.46 (d, J = 3.6 Hz, 1H), 7.53 (d, J = 8.1 Hz, 1H), 7.70-7.85 (m, 2H), 7.90-7.95 (m, 1H), 8.10-8.15 (m, 1H), 9.40 (s, 1H).

LC/MS: condition 3, retention time = 2.56 min LC/MS(ESI ) m/z; 578 [M+H] H-NMR (CDCl ) δ : -0.07 (s, 9H), 0.88-0.96 (m, 5H), 1.82-1.98 (m, 1H), 2.10-2.29 (m, 1H), 2.55-2.70 (m, 1H), 3.08-3.21 (m, 1H), 3.42-3.64 (m, 4H), 3.70-3.82 (m, 1H), 5.40-5.50 (m, 1H), 5.80 (s, 2H), 6.40 (d, J = 7.8 Hz, 1H), 6.68 (d, J = 3.9Hz, 1H), 7.46 (d, 62 J = 3.9 Hz, 1H), 7.60 (d, J = 7.8 Hz, 1H), 7.76 (t, J = 7.8 Hz, 1H), 7.95 (d, J = 7.8 Hz, 1H), 8.06 (d, J = 7.8 Hz, 1H), 8.12 (s, 1H), 9.41 (s, 1H).

LC/MS: condition 3, retention time = 2.59 min LC/MS(ESI ) m/z; 578 [M+H] H-NMR (CDCl ) δ : -0.07 (s, 9H), 0.82-0.99 (m, 2H), 1.03 (d, J = 6.9 Hz, 3H), 1.26 (t, J = 7.2 Hz, 3H), 1.70-1.85 (m, 1H), 2.65-2.80 (m, 1H), 3.24-3.42 (m, 1H), 3.57 (t, J = 8.4 Hz, 2H), 3.66-3.84 (m, 1H), 3.90-4.02 (m, 1H), 4.10-4.29 (m, 4H), .12-5.22 (m, 1H), 5.76-5.84 (m, 2H), 6.40 (d, J = 7.8 Hz, 1H), 6.72 (d, J = 3.9 Hz, 1H), 7.44 (d, J = 3.9 Hz, 1H), 7.54 (d, J = 3.9 Hz, 1H), 9.43 (s, 1H).

LC/MS: condition 1, retention time = 4.27 min LC/MS(ESI ) m/z; 485 [M+H] LC/MS(ESI ) m/z; 529 [M+HCOO] H-NMR (CDCl ) δ: -0.08 (s, 9H), 0.92 (t, J = 8.4 Hz, 2H), 1.04 (d, J = 6.9 Hz, 3H), 1.80-1.95 (m, 1H), 2.08-2.25 (m ,1H), 2.70-2.88 (m, 1H), 3.42-3.60 (m, 1H), 3.56 (t, J = 8.4 Hz, 2H), 3.65-3.82 (m, 2H), 4.32-4.46 (m, 1H), 5.21-5.38 (m, 1H), 5.78 (s, 2H), 6.38 (d, J = 7.8 Hz, 1H), 6.72 (d, J = 4.2 Hz, 1H), 6.95-7.10 (m, 1H), 7.20 (t, J = 8.1 Hz, 1H), 7.44 (d, J = 3.6 Hz, 1H), 7.45-7.60 (m, 3H), 7.99 (d, J = 8.1 Hz, 1H), 9.38 (s, 1H).

LC/MS: condition 3, retention time = 2.60 min LC/MS(ESI ) m/z; 600 [M+H] LC/MS(ESI ) m/z; 598 [M-H] TABLE 52 Rf Data H-NMR (CDCl ) δ : -0.09 (s, 9H), 0.80-0.92 (m, 2H), 0.95 (d, J = 7.2 Hz, 3H), 1.70-1.84 (m, 1H), 2.06-2.22 (m, 1H), 2.60-2.73 (m, 1H), 3.11-3.28 (m, 1H), 3.37-3.59 (m, 2H), 3.78-3.91 (m, 1H), 4.27-4.41 (m, 1H), 4.50-4.63 (m, 1H), 5.09-5.20 (m, 1H), 5.47 (d, J = 10.8 Hz, 1H), 5.63 (d, J = 10.2 Hz, 1H), 6.04 (d, J = 7.8 Hz, 65 1H), 6.67 (d, J = 3.9 Hz, 1H), 7.17-7.40 (m, 3H), 7.41 (d, J = 3.6 Hz, 1H), 7.78 ( d, J = 8.7 Hz, 1H), 8.07 (s, 1H), 8.74 (s, 1H), 9.66 (br s, 1H).

LC/MS: condition 3, retention time = 2.74 min LC/MS(ESI ) m/z; 600 [M+H] LC/MS(ESI ) m/z; 598 [M-H] LC/MS: condition 3, retention time = 2.62 min 66 LC/MS(ESI ) m/z; 585 [M+H] LC/MS: condition 3, retention time = 2.68 min LC/MS(ESI ) m/z; 585 [M+H] LC/MS: condition 3, retention time = 2.51 min LC/MS(ESI ) m/z; 549 [M+H] H-NMR (CDCl ) δ : -0.06 (s, 9H), 0.82-0.99 (m, 5H), 1.80-1.96 (m, 1H), 2.09-2.28 (m, 1H), 2.51-2.68 (m, 1H), 3.07-3.26 (m, 1H), 3.42-3.63 (m, 4H), 3.70-3.81 (m, 1H), 5.39-5.48 (m, 1H), 5.80 (dd, .5, 12.9 Hz, 2H), 6.39 (d, J = 7.8 Hz, 1H), 6.67 (d, J = 3.9 69 Hz, 1H), 7.45 (d, J = 4.2 Hz, 1H), 7.63 (d, J = 8.1 Hz, 1H), 7.77 (t, J = 7.8 Hz, 1H), 7.95 (d, J = 8.1 Hz, 1H), 8.03 (d, J = 7.8 Hz, 1H), 8.09 (s, 1H), 9.42 (s, 1H).

LC/MS: condition 3, retention time = 2.82 min LC/MS(ESI ) m/z; 621 [M+H] LC/MS: condition 1, retention time = 2.69 min 70 LC/MS(ESI ) m/z; 585 [M+H] LC/MS(ESI ) m/z; 629 [M+HCOO] LC/MS: condition 3, retention time = 2.72 min LC/MS(ESI ) m/z; 547 [M+H] LC/MS: condition 1, retention time = 2.88 min LC/MS(ESI ) m/z; 222 [M+H] LC/MS: condition 1, retention time = 3.86 min 73 LC/MS(ESI ) m/z; 540 [M+H] LC/MS(ESI ) m/z; 538 [M-H] LC/MS: condition 1, retention time = 3.52 min 74 LC/MS(ESI ) m/z; 235 [M+H] LC/MS(ESI ) m/z; 233 [M-H] LC/MS: condition 1, retention time = 3.97 min 75 LC/MS(ESI ) m/z; 553 [M+H] LC/MS(ESI ) m/z; 551 [M-H] LC/MS: condition 1, retention time = 4.34 min 76 LC/MS(ESI ) m/z; 509 [M+H] LC/MS(ESI ) m/z; 553 [M+HCOO] LC/MS: condition 1, retention time = 1.26 min LC/MS(ESI ) m/z; 571 [M+H] TABLE 53 Rf Data LC/MS: condition 1, retention time = 4.21 min 78 LC/MS(ESI ) m/z; 571 [M+H] LC/MS(ESI ) m/z; 615 [M+HCOO] LC/MS: condition 1, retention time = 4.85 min LC/MS(ESI ) m/z; 571 [M+H] LC/MS: condition 1, retention time = 3.89 min 80 LC/MS(ESI ) m/z; 528 [M+H] LC/MS(ESI ) m/z; 572 [M+HCOO] LC/MS: condition 1, retention time = 4.45 min LC/MS(ESI ) m/z; 528 [M+H] LC/MS: condition 1, retention time = 3.89 min LC/MS(ESI ) m/z; 528 [M+H] H-NMR (CDCl ) δ : -0.15 (s, 9H), 0.93 (t, J = 8.1 Hz, 2H), 1.01 (d, J = 7.2 Hz, 3H), 1.44 (s, 9H), 1.70-1.80 (m, 1H), 1.95-2.10 (m, 1H), 2.60-2.77 (m, 1H), 3.25-3.45 (m, 1H), 3.57 (t, J = 8.1 Hz, 2H), 3.64-3.90 (m, 2H), 4.00-4.20 (m, 1H), 5.10-5.22 (m, 1H), .80 (dd, J = 10.8, 13.2 Hz, 2H), 6.48 (d, J = 8.1 Hz, 1H), 6.72 (d, J = 3.6 Hz, 1H), 7.44 (d, J = 4.2 Hz, 1H), 7.57 (d, J = 8.4 Hz, 1H), 9.43 (s, 1H).

LC/MS: condition 1, retention time = 4.55 min LC/MS(ESI ) m/z; 513 [M+H] LC/MS(ESI ) m/z; 557 [M+HCOO] H-NMR (CDCl ) δ : -0.04 (s, 9H), 0.87-1.08 (m, 5H), 1.71-2.10 (m, 2H), 2.40-3.30 (m, 8H), 3.58-3.72 (m, 2H), 5.40-5.54 (m, 1H), .80-5.94 (m, 2H), 6.37 (d, J = 7.8 Hz, 1H), 6.87 (d, J = 3.9 Hz, 84 1H), 6.99-7.15 (m, 2H), 7.15-7.30 (m, 2H), 7.30-7.45 (m, 1H), 7.49 (d, J = 3.6 Hz, 1H), 8.44 (br s, 1H), 9.50 (s, 1H).

LC/MS: condition 3, retention time = 2.14 min LC/MS(ESI ) m/z; 535 [M+H] LC/MS: condition 3, retention time = 1.89 min LC/MS(ESI ) m/z; 481 [M+H] LC/MS: condition 3, retention time = 3.17 min LC/MS(ESI ) m/z; 579 [M+H] LC/MS: condition 3, retention time = 3.09 min LC/MS(ESI ) m/z; 579 [M+H] LC/MS: condition 3, retention time = 2.66 min LC/MS(ESI ) m/z; 327, 329 [M+H] LC/MS(ESI ) m/z; 325, 327 [M-H] H-NMR (CDCl ) δ : -0.06 (s, 9H), 0.91 (t, J = 8.4 Hz, 2H), 3.53 (t, J = 8.4 Hz, 2H), 5.68 (s, 2H), 6.71 (d, J = 3.6 Hz, 1H), 7.45 88 (d, J = 3.9 Hz, 1H), 8.81 (s, 1H).

LC/MS: condition 3, retention time = 2.40 min LC/MS(ESI ) m/z; 326, 328 [M+H] TABLE 54 Rf Data H-NMR (CDCl ) δ : -0.06 (s, 9H), 0.90 (t, J = 7.5 Hz, 2H), 1.60-1.84 (m, 2H), 2.07-2.19 (m, 2H), 2.21-2.38 (m, 2H), 2.77-2.91 (m, 2H), 3.46 (m, 4H), 3.92-4.10 (m, 1H), 5.57 (s, 4H), 89 6.58 (d, J = 3.6 Hz, 1H), 7.08 (d, J = 3.9 Hz, 1H), 7.20-7.38 (m, 5H), 8.30 (s, 1H), 9.39 (d, J = 7.5 Hz, 1H).

LC/MS: condition 3, retention time = 1.89 min LC/MS(ESI ) m/z; 480 [M+H] H-NMR (CDCl ) δ : -0.05 (s, 9H), 0.93 (t, J = 8.7 Hz, 2H), 1.80-1.96 (m, 2H), 2.10-2.28 (m, 1H), 2.94-3.22 (m, 4H), 3.56 (t, J = 8.7 Hz, 2H), 3.59 (s, 2H), 4.68-4.85 (m, 1H), 5.73 (s, 2H), 6.74 (d, J = 3.3 Hz, 1H), 7.22-7.48 (m, 6H), 8.03 (s, 1H), 9.04 (s, 1H).

LC/MS: condition 3, retention time = 2.18 min LC/MS(ESI ) m/z; 506 [M+H] LC/MS: condition 3, retention time = 1.90 min LC/MS(ESI ) m/z; 416 [M+H] H-NMR (CDCl ) δ : -0.04 (s, 9H), 0.94 (t, J = 8.1 Hz, 2H), 1.84-1.98 (m, 2H), 2.18-2.32 (m, 2H), 3.00-3.18 (m, 4H), 3.57 (t, J = 8.1 Hz, 2H), 3.65 (s, 2H), 4.70-4.84 (m, 1H), 5.75 (s, 2H), 6.73 (d, J = 3.6 Hz, 1H), 7.45 (d, J = 3.9 Hz, 1H), 7.53 (d, J = 8.4 Hz, 2H), 7.64 (d, J = 8.1 Hz, 2H), 8.09 (s, 1H), 9.06 (s, 1H).

LC/MS: condition 3, retention time = 2.23 min LC/MS(ESI ) m/z; 531 [M+H] H-NMR (CDCl ) δ : -0.05 (s, 9H), 0.93 (t, J = 7.5 Hz, 2H), 1.81-1.96 (m, 2H), 2.18-2.30 (m, 2H), 2.93-3.26 (m, 4H), 3.51-3.62 (m, 2H), 3.71 (s, 2H), 4.66-4.83 (m, 1H), 5.74 (s, 2H), 93 6.66-6.80 (m, 2H), 7.44 (d, J = 4.2 Hz, 1H), 8.03 (br s, 1H), 9.05 (s, 1H).

LC/MS: condition 3, retention time = 2.21 min LC/MS(ESI ) m/z; 546, 548 [M+H] H-NMR (CDCl ) δ : -0.05 (s, 9H), 0.93 (t, J = 8.1 Hz, 2H), 1.80-1.96 (m, 2H), 2.13-2.30 (m, 2H), 2.95-3.16 (m, 4H), 3.56 (t, J = 8.1 Hz, 2H), 3.64 (s, 2H), 4.70-4.82 (m, 1H), 5.74 (s, 2H), 94 6.73 (d, J = 3.9 Hz, 1H), 7.40-7.68 (m, 5H), 8.14 (s, 1H), 9.05 (s, 1H).

LC/MS: condition 3, retention time = 2.43 min LC/MS(ESI ) m/z; 574 [M+H] LC/MS: condition 3, retention time = 2.87 min LC/MS(ESI ) m/z; 415 [M+H] H-NMR (CDCl ) δ : -0.06 (s, 9H), 0.88 (t, J = 8.1 Hz, 2H), 2.76 96 (s, 3H), 3.48-3.62 (m, 2H), 5.67 (s, 2H), 6.74 (d, J = 3.3 Hz, 1H), 7.43 (d, J = 3.9 Hz, 1H), 8.72 (s, 1H).

LC/MS: condition 1, retention time = 3.32 min LC/MS(ESI ) m/z; 479 [M+H] LC/MS: condition 1, retention time = 3.18 min LC/MS(ESI ) m/z; 489 [M+H] LC/MS: condition 1, retention time = 2.88 min LC/MS(ESI ) m/z; 399 [M+H] TABLE 55 Rf Data LC/MS: condition 1, retention time = 3.50 min LC/MS(ESI ) m/z; 529, 531 [M+H] LC/MS: condition 1, retention time = 3.50 min LC/MS(ESI ) m/z; 557 [M+H] LC/MS: condition 1, retention time = 3.26 min LC/MS(ESI ) m/z; 514 [M+H] LC/MS: condition 1, retention time = 2.98 min LC/MS(ESI ) m/z; 532 [M+H] LC/MS: condition 1, retention time = 0.35 min LC/MS(ESI ) m/z; 335 [M+H] LC/MS: condition 1, retention time = 3.30 min LC/MS(ESI ) m/z; 465 [M+H] H-NMR (CDCl ) δ :-0.07 (s, 9H), 0.85-0.98 (m, 2H), 1.52-1.79 (m, 2H), 2.04-2.38 (m, 4H), 2.79-2.95 (m, 2H), 3.44-3.62 (m, 4H), 106 3.89-4.06 (m, 1H), 4.70 (s, 2H). 5.58 (s, 2H), 6.49 (d, J = 3.6 Hz, 1H), 7.11 (d, J = 3.9 Hz, 1H), 7.23-7.40 (m, 5H), 7.82 (s, 1H).

H-NMR (CD OD) δ :-0.03 (s, 9H), 0.92 (t, J = 8.0 Hz, 2H), 1.70-1.91 (m, 2H), 2.12-2.51 (m, 4H), 2.90-3.10 (m, 2H), 3.54-3.78 (m, 4H), 3.96 (s, 2H), 4.02-4.19 (m, 1H), 5.61 (s, 2H), 107 6.65 (d, J = 4.2 Hz, 1H), 7.28 (d, J = 3.6 Hz, 1H), 7.31-7.53 (m, 5H), 7.84 (s, 1H).

LC/MS: condition 1, retention time = 0.37 min LC/MS(ESI ) m/z; 466 [M+H] LC/MS: condition 1, retention time = 3.24 min LC/MS(ESI ) m/z; 492 [M+H] LC/MS: condition 1, retention time = 2.96 min LC/MS(ESI ) m/z; 402 [M+H] LC/MS: condition 1, retention time = 4.45 min LC/MS(ESI ) m/z; 556 [M+H] H-NMR (CDCl ) δ :-0.05 (s, 9H), 0.81-1.06 (m, 2H), 1.55-2.05 (m, 3H), 2.05-2.29 (m, 1H), 2.93-3.20 (m, 4H), 3.46-3.70 (m, 4H), 4.11-4.28 (m, 1H), 4.29-4.49 (m, 2H), 5.13 (s, 1H), 5.65 (s, 2H), 111 6.47 (d, J = 3.6 Hz, 1H), 7.21-7.41 (m, 2H), 7.78 (d, J = 7.7 Hz, 1H), 7.98 (s, 1H), 8.45-8.67 (m, 2H).

LC/MS: condition 1, retention time = 2.92 min LC/MS(ESI ) m/z; 493 [M+H] LC/MS: condition 1, retention time = 3.26 min LC/MS(ESI ) m/z; 517 [M+H] LC/MS: condition 1, retention time = 3.48 min LC/MS(ESI ) m/z; 560 [M+H] H-NMR (CDCl ) δ :-0.03 (s, 9H), 0.87-1.05 (m, 2H), 1.50-1.89 (m, 4H), 2.02-2.28 (m, 2H), 2.92-3.25 (m, 2H), 3.60 (t, J = 8.3 Hz, 2H), 4.30-3.72 (m, 3H), 5.70 (s, 2H), 6.44 (d, J = 3.6 Hz, 1H), 114 7.37 (d, J = 3.9 Hz, 1H), 7.79 (s, 1H), 8.07 (s, 1H), 8.69 (s, 1H).

LC/MS: condition 1, retention time = 3.87 min LC/MS(ESI ) m/z; 529 [M+H] TABLE 56 Rf Data H-NMR (CDCl ) δ : -0.05 (s, 9H), 0.80-1.03 (m, 2H), 1.53-1.77 (m, 4H), 1.93-2.13 (m, 2H), 3.10-3.40 (m, 2H), 3.55 (t, J = 8.3 Hz, 2H), 3.90-4.07 (m, 1H), 4.31-4.53 (m, 2H), 4.82-4.98 (m, 1H), .21 (s, 1H), 5.67 (s, 2H), 6.35-6.48 (m, 1H), 7.35 (d, J = 3.6 Hz, 1H), 8.01 (s, 1H).

LC/MS: condition 1, retention time = 4.17 min LC/MS(ESI ) m/z; 512 [M+H] LC/MS: condition 1, retention time = 2.99 min LC/MS(ESI ) m/z; 499 [M+H] LC/MS: condition 1, retention time = 0.52 min LC/MS(ESI ) m/z; 349 [M+H] LC/MS: condition 1, retention time = 3.57 min LC/MS(ESI ) m/z; 479 [M+H] LC/MS: condition 1, retention time = 2.91 min LC/MS(ESI ) m/z; 481 [M+H] LC/MS: condition 1, retention time = 3.42 min LC/MS(ESI ) m/z; 480 [M+H] LC/MS: condition 1, retention time = 3.36 min LC/MS(ESI ) m/z; 506 [M+H] H-NMR (CDCl ) δ : 0.92-1.19 (m, 4H), 1.41-1.51 (m, 1H), 1.74-1.96 (m, 4H), 2.55-2.68 (m, 1H), 3.45 (d, J = 6.3 Hz, 2H).

LC/MS: condition 3, retention time = 0.29 min LC/MS(ESI ) m/z; 130 [M+H] LC/MS: condition 3, retention time = 2.33 min LC/MS(ESI ) m/z; 418 [M+H] LC/MS: condition 3, retention time = 2.16 min LC/MS(ESI ) m/z; 428 [M+H] LC/MS: condition 1, retention time = 3.62 min LC/MS(ESI ) m/z; 230 [M+H] LC/MS: condition 1, retention time = 0.39 min LC/MS(ESI ) m/z; 130 [M+H] LC/MS: condition 1, retention time = 4.43 min LC/MS(ESI ) m/z; 418 [M+H] LC/MS: condition 1, retention time = 4.08 min LC/MS(ESI ) m/z; 428 [M+H] LC/MS: condition 1, retention time = 3.58 min LC/MS(ESI ) m/z; 547 [M+H] LC/MS: condition 1, retention time = 3.52 min LC/MS(ESI ) m/z; 524 [M+H] LC/MS: condition 1, retention time = 3.38 min LC/MS(ESI ) m/z; 551 [M+H] LC/MS: condition 1, retention time = 3.34 min LC/MS(ESI ) m/z; 525 [M+H] LC/MS: condition 1, retention time = 3.56 min LC/MS(ESI ) m/z; 557, 558, 559 [M+H] TABLE 57 Rf Data LC/MS: condition 1, retention time = 3.46 min LC/MS(ESI ) m/z; 558 [M+H] LC/MS: condition 1, retention time = 3.44 min LC/MS(ESI ) m/z; 530, 532 [M+H] LC/MS: condition 1, retention time = 3.56 min LC/MS(ESI ) m/z; 575 [M+H] LC/MS: condition 1, retention time = 3.28 min LC/MS(ESI ) m/z; 540 [M+H] LC/MS: condition 1, retention time = 3.30 min LC/MS(ESI ) m/z; 557, 559 [M+H] LC/MS: condition 1, retention time = 3.56 min LC/MS(ESI ) m/z; 573, 575 [M+H] LC/MS: condition 1, retention time = 3.50 min LC/MS(ESI ) m/z; 573, 575 [M+H] LC/MS: condition 1, retention time = 3.44 min LC/MS(ESI ) m/z; 574, 576 [M+H] LC/MS: condition 1, retention time = 3.46 min LC/MS(ESI ) m/z; 569 [M+H] LC/MS: condition 1, retention time = 3.19 min LC/MS(ESI ) m/z; 528 [M+H] LC/MS: condition 1, retention time = 4.33 min LC/MS(ESI ) m/z; 543, 545 [M+H] TABLE 58 Rf Data LC/MS: condition 3, retention time = 2.21 min LC/MS(ESI ) m/z; 559 [M+H] LC/MS: condition 3, retention time = 2.32 min LC/MS(ESI ) m/z; 590, 592 [M+H] LC/MS: condition 3, retention time = 2.22 min LC/MS(ESI ) m/z; 544 [M+H] LC/MS: condition 3, retention time = 2.05 min LC/MS(ESI ) m/z; 470 [M+H] LC/MS: condition 3, retention time = 2.19 min LC/MS(ESI ) m/z; 486 [M+H] LC/MS: condition 3, retention time = 2.02 min LC/MS(ESI ) m/z; 528 [M+H] H-NMR (CDCl ) δ : -0.04 (s, 9H), 0.91-0.97 (m, 2H), 1.98 (d, J = 12.3 Hz, 2H), 2.59 (t, J = 11.7 Hz, 2H), 3.00-3.15 (m, 4H), 3.54-3.59 (m, 2H), 3.66 (s, 2H), 4.73-4.81 (m, 1H), 5.75 (s, 2H), 151 6.84 (d, J = 3.9 Hz, 1H), 7.48 (d, J = 3.6 Hz, 1H), 8.32 (br s, 1H), 9.06 (s, 1H).

LC/MS: condition 3, retention time = 2.35 min LC/MS(ESI ) m/z; 455 [M+H] H-NMR (CDCl ) δ : -0.05 (s, 9H), 0.94 (t, J = 8.3 Hz, 2H), 1.87 (d, J = 10.8 Hz, 2H), 2.67 (t, J = 12 Hz, 2H), 2.98-3.21 (m, 6H), 3.56 (t, J = 8.3 Hz, 2H), 4.71-4.79 (m, 1H), 5.74 (s, 2H), 6.71 152 (d, J = 3.9 Hz, 1H), 7.45 (d, J = 3.9 Hz, 1H), 8.08 (br s, 1H), 9.05 (s, 1H).

LC/MS: condition 3, retention time = 2.71 min LC/MS(ESI ) m/z; 498 [M+H] LC/MS: condition 3, retention time = 2.00 min LC/MS(ESI ) m/z; 497 [M+H] LC/MS: condition 3, retention time = 2.33 min LC/MS(ESI ) m/z; 554 [M+H] LC/MS: condition 3, retention time = 1.99 min LC/MS(ESI ) m/z; 483 [M+H] LC/MS: condition 3, retention time = 2.05 min LC/MS(ESI ) m/z; 500 [M+H] H-NMR (CDCl ) δ : -0.04 (s, 9H), 0.93 (t, J = 8.4 Hz, 2H), 1.90 (d, J = 12.3 Hz, 2H), 2.32 (t, J = 11.1 Hz, 2H), 2.57 (t, J = 7.1 Hz, 2H), 2.81 (t, J = 6.9 Hz, 2H), 3.01-3.17 (m, 4H), 3.56 (t, J = 8.3 Hz, 2H), 4.71-4.79 (m, 1H), 5.74 (s, 2H), 6.72 (d, J = 3.9 Hz, 1H), 7.45 (d, J = 3.9 Hz, 1H), 8.12 (br s, 1H), 9.05 (s, 1H).

LC/MS: condition 3, retention time = 1.97 min LC/MS(ESI ) m/z; 469 [M+H] LC/MS: condition 1, retention time = 0.33 min LC/MS(ESI ) m/z; 168 [M+H] TABLE 59 Rf Data H-NMR (CDCl ) δ : 1.52-1.80 (m, 9H), 2.05-2.25 (m, 3H), 3.60-3.75 (m, 1H), 4.90-5.15 (m, 1H), 5.10 (s, 2H), 7.25-7.45 159a (m, 5H).

LC/MS: condition 1, retention time = 3.63 min LC/MS(ESI ) m/z; 302 [M+H] H-NMR (CDCl ) δ : 1.41-1.53 (m, 3H), 1.53-1.91 (m, 7H), 2.01-2.25 (m, 3H), 3.73-3.86 (m, 1H), 4.98-5.02 (m, 1H), 5.10 159b (s, 2H), 7.28-7.43 (m, 5H).

LC/MS: condition 1, retention time = 3.63 min LC/MS(ESI ) m/z; 302 [M+H] H-NMR (DMSO-d ) δ: 1.20 (d, J = 12.3 Hz, 2H), 1.57 (m, 5H), 1.72 (s, 1H), 1.92-1.96 (m, 5H), 2.83 (s, 1H), 4.26 (br s, 1H).

LC/MS: condition 1, retention time = 0.33 min LC/MS(ESI ) m/z; 168 [M+H] H-NMR (DMSO-d ) δ : 1.27 (d, J = 12.7 Hz, 2H), 1.41-1.63 (m, 6H), 1.76-2.02 (m, 5H), 2.75-2.80 (br s, 1H).

LC/MS: condition 1, retention time = 0.33 min LC/MS(ESI ) m/z; 168 [M+H] 162 H-NMR (CDCl ) δ : 1.48 (s, 9H), 4.70 (s, 4H).

H-NMR (CDCl ) δ : 1.46 (s, 9H), 4.58-4.65 (m, 2H), 4.68-4.74 (m, 2H), 5.36-5.41 (m, 1H).

LC/MS: condition 1, retention time = 3.44 min LC/MS(ESI ) m/z; 195 [M+H] H-NMR (CDCl ) δ : 1.44 (s, 9H), 2.64 (d, J = 7.2 Hz, 2H), 2.79-2.94 (m, 1H), 3.69 (dd, J = 8.8, 5.5 Hz, 2H), 4.13 (dd, J 164 = 8.8, 8.3 Hz, 2H).

LC/MS: condition 1, retention time = 3.20 min LC/MS(ESI ) m/z; 197 [M+H] LC/MS: condition 1, retention time = 0.33 min LC/MS(ESI ) m/z; 97 [M+H] H-NMR (CDCl ) δ: -0.05 (s, 9H), 0.95 (t, J = 8.4 Hz, 2H), 1.23 (m, 2H), 1.47 (m, 3H), 2.00 (d, J = 8.7 Hz, 2H), 2.33 (d, J = 8.7 Hz, 2H), 3.58 (m, 4H), 5.63 (br s, 4H), 6.62 (d, J = 4.0 Hz, 166 1H), 7.13 (d, J = 4.0 Hz, 1H), 8.33 (s, 1H), 9.29 (d, J = 7.8 Hz, 1H).

LC/MS: condition 3, retention time = 1.99 min LC/MS(ESI ) m/z; 419 [M+H] H-NMR (CDCl ) δ: -0.04 (s, 9H), 0.97 (t, J = 8.4 Hz, 2H), 1.28 (m, 2H), 1.43 (m, 1H), 1.74 (m, 1H), 2.09 (m, 4H), 2.80 (m, 2H), 3.60 (t, J = 8.4 Hz, 2H), 3.60 (m, 2H), 4.75 (m, 1H), 5.78 (s, 167 2H), 6.74 (d, J = 4.0 Hz, 1H), 7.47 (d, J = 4.0 Hz, 1H), 8.41 (s, 1H), 9.10 (s, 1H).

LC/MS: condition 3, retention time = 2.33 min LC/MS(ESI ) m/z; 445 [M+H] TABLE 60 Rf Data H-NMR (CDCl ) δ : -0.04 (s, 9H), 0.95 (t, J = 8.1 Hz, 2H), 1.53 (m, 2H), 2.06 (m, 4H), 2.42 (m, 1H), 2.85 (m, 2H), 3.60 (t, J = 8.1 Hz, 2H), 4.75 (m, 1H), 5.78 (br s, 2H), 6.70 (d, J = 4.0 Hz, 1H), 7.79 (d, J = 4.0 Hz, 1H), 8.67 (br s, 1H), 9.10 (s, 1H), 9.79 (s, 1H).

LC/MS: condition 3, retention time = 2.52 min LC/MS(ESI ) m/z; 443 [M+H] H-NMR (CDCl ) δ : -0.06 (s, 9H), 0.96 (t, J = 8.1 Hz, 2H), 1.19 (m, 2H), 1.30 (br s, 1H), 1.67 (br s, 1H), 2.07 (m, 4H), 2.08 (m, 2H), 2.80 (m, 2H), 3.25 (m, 2H), 3.60 (t, J = 8.1 Hz, 2H), 4.74 169 (m, 1H), 5.78 (br s, 2H), 6.73 (d, J = 4.0 Hz, 1H), 7.47 (d, J = 4.0 Hz, 1H), 9.10 (s, 1H).

LC/MS: condition 3, retention time = 2.27 min LC/MS(ESI ) m/z; 526 [M+H] H-NMR (CDCl ) δ : -0.06 (s, 9H), 0.92 (t, J = 8.1 Hz, 2H), 1.88 (m, 2H), 2.03 (m, 4H), 2.37 (m, 1H), 2.85 (m, 2H), 3.53 (t, J = 8.1 Hz, 2H), 4.70 (m, 1H), 5.34 (m, 1H), 5.72 (br s, 2H), 6.30-6.74 170 (m, 1H), 6.70 (d, J = 4.0 Hz, 1H), 7.44 (d, J = 4.0 Hz, 1H), 9.04 (s, 1H), 9.31 (s, 1H).

LC/MS: condition 3, retention time = 2.65 min LC/MS(ESI ) m/z; 446 [M+H] LC/MS: condition 3, retention time = 2.23 min LC/MS(ESI ) m/z; 457 [M+H] LC/MS: condition 3, retention time = 2.23 min LC/MS(ESI ) m/z; 457 [M+H] LC/MS: condition 3, retention time = 2.46 min LC/MS(ESI ) m/z; 483 [M+H] LC/MS: condition 3, retention time = 2.28 min LC/MS(ESI ) m/z; 483 [M+H] H-NMR (CDCl ) δ : -0.04 (s, 9H), 0.91 (t, J = 7.3 Hz, 2H), 1.53-1.88 (m, 8H), 2.02-2.12 (m, 2H), 2.18-2.27 (m, 1H), 2.37-2.49 (m, 2H), 2.63 (s, 3H), 3.54 (d, J = 7.3 Hz, 2H), 4.05-4.20 (m, 1H), 5.61 (s, 2H), 6.53 (d, J = 3.6 Hz, 1H), 7.07 (d, J = 3.6 Hz, 1H), 8.67 (s, 1H), 10.78 (d, J = 7.6 Hz, 1H).

LC/MS: condition 1, retention time = 4.23 min LC/MS(ESI ) m/z; 456 [M+H] LC/MS(ESI ) m/z; 500 [M+HCOO] H-NMR (CDCl ) δ : -0.05 (s, 9H), 0.91 (t, J = 8.3 Hz, 2H), 1.40-1.62 (m, 4H), 1.73-2.13 (m, 6H), 2.18-2.28 (m, 1H), 2.30-2.42 (m, 2H), 2.65 (s, 3H), 3.54 (d, J = 8.3 Hz, 2H), 4.19-4.30 (m, 1H), 5.58 (s, 2H), 6.51 (d, J = 4.0 Hz, 1H), 7.07 (d, J = 4.0 Hz, 1H), 8.66 (s, 1H), 10.75 (d, J = 8.0 Hz, 1H).

LC/MS: condition 1, retention time = 4.07 min LC/MS(ESI ) m/z; 456 [M+H] LC/MS(ESI ) m/z; 500 [M+HCOO] TABLE 61 Rf Data LC/MS: condition 3, retention time = 2.33 min LC/MS(ESI ) m/z; 466 [M+H] LC/MS: condition 3, retention time = 2.15 min LC/MS(ESI ) m/z; 466 [M+H] H-NMR (CDCl ) δ : 3.01 (d, J = 13.2 Hz, 1H), 3.62 (d, J = 13.2 Hz, 1H), 7.35 (m, 1H), 7.93 (m, 1H), 8.60 (m, 1H), 8.78 (s, 1H).

LC/MS: condition 3, retention time = 0.39 min LC/MS(ESI ) m/z; 207 [M+H] TABLE 62 Ex Data H-NMR (CDCl ) δ : 1.10-2.00 (m, 10H), 1.58 (d, J = 6.3 Hz, 3H), 3.90-4.10 (m, 1H), 4.67 (d, J = 10.2 Hz, 1H), 4.83 (d, J = 10.2 Hz, 1H), 5.13 (q, J = 6.6 Hz, 1H), 6.43 (.d, J = 3.6 Hz, 1H), 7.17 (d, J = 3.3 Hz, 1H), 7.89 (s, 1H), 9.29 (br s, 1H).

LC/MS: condition 1, retention time = 2.82 min LC/MS(ESI ) m/z; 272 [M+H] H-NMR (CDCl ) δ : 1.10-1.90 (m, 8H), 1.95-2.10 (m, 2H), 3.95-4.10 (m, 1H), 4.78 (s, 2H), 4.96 (s, 2H), 6.43 (d, J = 3.6 Hz, 1H), 7.17 (d, J = 3.3 Hz, 1H), 7.81 (s, 1H), 9.45 (br s, 1H).

LC/MS: condition 1, retention time = 2.37 min LC/MS(ESI ) m/z; 258 [M+H] H-NMR (CDCl ) δ : 1.50-2.00 (m, 6H), 2.00-2.15 (m, 2H), 2.20-2.35 (m, 2H), 4.90-5.05 (m, 1H), 6.46 (d, J = 7.8 Hz, 1H), 6.80-6.85 (m, 1H), 7.40-7.50 (m, 1H), 7.80 (d, J = 8.1 Hz, 1H), 9.46 (s, 1H), 11.25 (br s, 1H).

LC/MS: condition 1, retention time = 3.32 min LC/MS(ESI ) m/z; 268 [M+H] LC/MS: condition 1, retention time = 0.79 min LC/MS(ESI ) m/z; 373 [M+H] LC/MS: condition 1, retention time = 0.50 min LC/MS(ESI ) m/z; 283 [M+H] H-NMR (CDCl ) δ : 0.87 (d, J = 7.2 Hz, 3H), 1.60-2.00 (m, 2H), 2.40-2.60 (m, 2H), 2.75-3.00 (m, 2H), 3.00-3.20 (m, 1H), 3.70 (s, 2H), 5.40-5.50 (m, 1H), 6.42 (d, J = 7.8 Hz, 1H), 6.80-6.85 (m, 6a 1H), 7.00-7.20 (m, 3H), 7.45-7.50 (m, 1H), 8.51 (br s, 1H), 9.46 (s, 1H), 11.77 (br s, 1H).

LC/MS: condition 1, retention time = 2.86 min LC/MS(ESI ) m/z; 409 [M+H] H-NMR (CDCl ) δ : 0.88 (d, J = 7.2 Hz, 3H), 1.60-2.00 (m, 2H), 2.37 (s, 3H), 2.40-2.55 (m, 2H), 2.55-2.70 (m, 1H), 2.80-2.90 (m, 1H), 2.95-3.05 (m, 1H), 5.40-5.50 (m, 1H), 6.42 (d, J = 8.4 Hz, 6b 1H), 6.83 (d, J = 3.3 Hz, 1H), 7.40-7.50 (m, 1H), 8.30-8.50 (m, 1H), 9.48 (s, 1H), 11.85 (br s, 1H).

LC/MS: condition 1, retention time = 0.50 min LC/MS(ESI ) m/z; 297 [M+H] H-NMR (CD OD) δ : 1.00-1.10 (m, 3H), 1.80-1.95 (m, 1H), 2.10-2.20 (m, 1H), 2.70-2.90 (m, 1H), 3.20-3.30 (m, 1H), 3.35 (s, 2H), 3.60-3.75 (m, 1H), 3.90-4.25 (m, 1H), 4.25-4.55 (m, 1H), 5.25-5.50 7 (m, 1H), 6.40-6.55 (m, 1H), 6.85-7.00 (m, 1H), 7.50-7.60 (m, 1H), 8.00-8.10 (m, 1H), 9.21 (s, 1H).

LC/MS: condition 1, retention time = 1.92 min LC/MS(ESI ) m/z; 350 [M+H] LC/MS: condition 1, retention time = 3.09 min 8 LC/MS(ESI ) m/z; 365 [M+H] LC/MS(ESI ) m/z; 363 [M-H] TABLE 63 Ex Data H-NMR (CD OD) δ : 1.01-1.08 (m, 3H), 1.77-1.91 (m, 1H), 2.11-2.19 (m, 1H), 2.74-2.85 (m, 1H), 3.11-3.18 (m, 1H), 3.59-3.82 (m, 3H), 4.00 (dd, J = 9.1, 12.7 Hz, 1H), 4.17 (d, J = 6.8 Hz, 1H), 4.35-4.49 (m, 1H), 5.30-5.44 (m, 1H), 6.40-6.45 (m, 1H), 6.86-6.88 (m, 1H), 7.53-7.55 (m, 1H), 8.00-8.05 (m, 1H), 9.21 (s, 1H).

LC/MS: condition 2, retention time = 3.29 min LC/MS(ESI ) m/z; 393 [M+1] LC/MS(ESI ) m/z; 391 [M-1] H-NMR (CDCl ) δ: 1.02 (d, J = 7.5 Hz, 3H), 1.15 (d, J = 7.2 Hz, 6H), 1.80-1.95 (m, 1H), 2.10-2.40 (m, 2H), 2.70-2.80 (m, 1H), 2.91 (d, J = 6.3 Hz, 2H), 3.25-3.40 (m, 1H), 3.50-3.70 (m, 1H), 3.70-3.80 (m, 1H), 3.85-4.00 (m, 1H), 5.40-5.55 (m, 1H), 6.41 (d, J = 7.8 Hz, 1H), 6.70-6.80 (m, 1H), 7.40-7.50 (m, 1H), 7.67 (d, J = 7.8 Hz, 1H), 9.39 (s, 1H), 11.91 (br s, 1H).

LC/MS: condition 1, retention time = 3.44 min LC/MS(ESI ) m/z; 403 [M+H] LC/MS(ESI ) m/z; 401 [M-H] H-NMR (CD OD) δ : 1.00 (d, J = 6.9 Hz, 3H), 1.85-2.00 (m, 1H), 2.10-2.25 (m, 1H), 2.65-2.80 (m, 1H), 3.50-3.70 (m, 2H), 3.90-4.10 (m, 2H), 4.31 (q, J = 9.6 Hz, 2H), 5.50-5.60 (m, 1H), 6.43 (d, J = 8.1Hz, 1H), 6.92 (d, J = 3.9 Hz, 1H), 7.57 (d, J = 3.6 Hz, 1H), 8.15 (d, J = 8.1 Hz, 1H), 9.22 (s, 1H).

LC/MS: condition 1, retention time = 3.37 min LC/MS(ESI ) m/z; 429 [M+H] LC/MS(ESI ) m/z; 427 [M-H] LC/MS: condition 1, retention time = 3.51 min 12 LC/MS(ESI ) m/z; 304 [M+H] LC/MS(ESI ) m/z; 302 [M-H] LC/MS: condition 1, retention time = 2.94 min LC/MS(ESI ) m/z; 269 [M+H] H-NMR (CDCl ) δ : 1.01 (d, J = 7.2 Hz, 3H), 1.53-1.92 (m, 4H), 2.09-2.38 (m, 2H), 2.48-2.73 (m, 2H), 2.75-2.99 (m, 1H), 3.37-2.58 (m, 2H), 4.45-4.62 (m, 1H), 4.88-5.01 (m, 2H), 6.41 (d, J = 3.6 Hz, 1H), 7.12 (d, J = 3.6 Hz, 1H), 7.30-7.35 (m, 5H), 7.75 (s, 1H), 9.40 (br s, 1H).

LC/MS: condition 1, retention time = 0.50 min LC/MS(ESI ) m/z; 273 [M+H] H-NMR (CDCl ) δ: 1.15-1.27 (m, 3H), 1.70-2.05 (m, 2H), 2.44-2.55 (m, 1H), 3.48-3.94 (m, 5H), 4.32-4.36 (m, 1H), 4.65-4.85 (m, 2H), 4.95-5.07 (m, 2H), 6.32-6.38 (m, 1H), 7.19-7.29 (m, 2H), 7.83-7.88 (m, 1H), 9.60-9.49 (m, 1H).

LC/MS: condition 1, retention time = 0.54 min LC/MS(ESI ) m/z; 340 [M+H] LC/MS: condition 1, retention time = 2.27 min LC/MS(ESI ) m/z; 271 [M+H] LC/MS: condition 1, retention time = 3.27 min LC/MS(ESI ) m/z; 269 [M+H] LC/MS: condition 1, retention time = 0.54 min LC/MS(ESI ) m/z; 255 [M+H] TABLE 64 Ex Data H-NMR (DMSO-d ) δ : 1.20-2.10 (m, 10H), 6.25 (d, J = 8.0 Hz, 1H), 6.42-6.58 (m, 1H), 8.22 (d, J = 8.0 Hz, 1H), 8.49 (s, 1H), 9.10 (s, 1H).

LC/MS: condition 1, retention time = 3.24 min LC/MS(ESI ) m/z; 269 [M+1] LC/MS(ESI ) m/z; 267 [M-1] TABLE 65 Ex Data H-NMR (CDCl ) δ : 0.23 (d, J = 6.9 Hz, 3H), 1.42-1.56 (m, 1H), 1.60-1.80 (m, 1H), 1.86-2.01 (m, 1H), 2.08-2.21 (m, 1H), 2.72-2.82 (m, 1H), 3.05-3.18 (m, 1H), 3.60 (s, 2H), 3.68 (d, J = 11.4 Hz, 1H), 5.50-5.58 (m, 1H), 6.48 (d, J = 7.8 Hz, 1H), 7.25-7.42 (m, 5H), 7.48 (s, 1H), 9.38 (s, 1H), 9.54 (d, J = 7.8 Hz, 1H).

LC/MS: condition 1, retention time = 3.31 min LC/MS(ESI ) m/z; 451, 453 [M+H] H-NMR (CDCl ) δ : 0.31 (d, J = 6.6 Hz, 3H), 1.40-1.55 (m, 1H), 1.60-1.85 (m, 1H), 1.90-2.05 (m, 1H), 2.10-2.25 (m, 1H), 2.70-2.80 (m, 1H), 3.05-3.20 (m, 1H), 3.50-3.65 (m, 1H), 3.59 (s, 2H), 5.45-5.50 (m, 1H), 6.48 (d, J = 8.1 Hz, 1H), 7.25-7.50 (m, 6H), 9.39 (s, 1H), 9.49 (d, J = 8.4 Hz, 1H), 11.9 (br s, 1H).

LC/MS: condition 1, retention time = 3.09 min LC/MS(ESI ) m/z; 407, 409 [M+H] LC/MS(ESI ) m/z; 405, 407 [M-H] H-NMR (CDCl ) δ : 0.86 (d, J = 6.9 Hz, 3H), 1.60-1.80 (m, 1H), 1.85-2.00 (m, 1H), 2.22 (s, 3H), 2.40-2.60 (m, 2H), 2.75-2.90 (m, 2H), 3.00-3.10 (m, 1H), 3.65 (dd, J = 22.2, 9.6 Hz, 2H), 5.40-5.50 (m, 1H), 6.80 (s, 1H), 7.20-7.50 (m, 6H), 8.58 (br s, 1H), 9.49 (s, 1H), 11.93 (br s, 1H).

LC/MS: condition 1, retention time = 1.00 min LC/MS(ESI ) m/z; 387 [M+H] LC/MS(ESI ) m/z; 385 [M-H] LC/MS: condition 1, retention time = 2.74 min 24 LC/MS(ESI ) m/z; 451, 453 [M+H] LC/MS(ESI ) m/z; 449, 451 [M-H] H-NMR (CD OD) δ : 0.95 (d, J = 7.2 Hz, 3H), 1.90-2.00 (m, 1H), 2.10-2.25 (m, 1H), 2.60-2,70 (m, 1H), 3.50-3.60 (m, 2H), 3.85-4.05 (m, 2H), 5.45-5.60 (m, 1H), 6.40 (d, J = 8.1 Hz, 1H), 6.82 (d, J = 3.9 Hz, 1H), 7.54 (d, J = 3.6 Hz, 1H), 7.80-7.90 (m, 2H), 8.00-8.05 (m, 1H), 8.10-8.15 (m, 1H), 8.16 (d, J = 7.8 Hz, 1H), 9.20 (s, 1H).

LC/MS: condition 3, retention time = 1.73 min LC/MS(ESI ) m/z; 448 [M+H] LC/MS(ESI ) m/z; 446 [M-H] LC/MS: condition 3, retention time = 1.78 min 26 LC/MS(ESI ) m/z; 448 [M+H] LC/MS(ESI ) m/z; 446 [M-H] H-NMR (CDCl ) δ : 1.04 (d, J = 6.9 Hz, 3H), 1.26 (t, J = 6.9 Hz, 3H), 1.70-1.86 (m, 1H), 2.00-2.18 (m, 1H), 2.68-2.84 (m, 1H), 3.28-3.50 (m, 1H), 3.68-3.88 (m, 1H), 3.88-4.02 (m, 1H), 4.05-4.38 (m, 3H), 5.15-5.25 (m, 1H), 6.43 (d, J = 7.8 Hz, 1H), 6.73 (br s, 1H), 7.32 (br s, 1H), 7.58 (d, J = 8.1 Hz, 1H), 9.47 (s, 1H), 11.51 (br s, 1H).

LC/MS: condition 3, retention time = 1.59 min LC/MS(ESI ) m/z; 355 [M+H] TABLE 66 Ex Data H-NMR (CDCl ) δ : 0.98 (d, J = 6.9 Hz, 3H), 1.77-1.88 (m, 1H), 2.16-2.31 (m, 1H), 2.68-2.82 (m, 1H), 3.26-3.42 (m, 1H), 3.90-4.05 (m, 1H), 4.10-4.28 (m, 1H), 4.44-4.59 (m, 1H), .38-5.50 (m, 1H), 6.18 (d, J = 7.8 Hz, 1H), 6.89 (br s, 1H), 7.31 28 (t, J = 7.5 Hz, 1H), 7.49-7.62 (m, 3H), 7.66 (d, J = 7.8 Hz, 1H), 7.75 (d, J = 7.8 Hz, 1H), 8.54 (br s, 1H).

LC/MS: condition 3, retention time = 1.78 min LC/MS(ESI ) m/z; 470 [M+H] LC/MS(ESI ) m/z; 468 [M-H] LC/MS: condition 3, retention time = 1.98 min 29 LC/MS(ESI ) m/z; 470 [M+H] LC/MS(ESI ) m/z; 468 [M-H] LC/MS: condition 3, retention time = 1.78 min LC/MS(ESI ) m/z; 455 [M+H] LC/MS(ESI ) m/z; 453 [M-H] H-NMR (CDCl ) δ : 1.10 (d, J = 7.2 Hz, 3H), 1.75-1.90 (m, 1H), 2.00-2.20 (m, 1H), 2.79-2.99 (m, 1H), 3.41-4.03 (m, 3H), 4.60-5.08 (m, 1H), 5.20-5.40 (m, 1H), 6.45 (d, J = 7.8 Hz, 1H), 31 6.70 (s, 1H), 7.42-7.86 (m, 6H), 9.46 (s, 1H), 12.14 (s, 1H).

LC/MS: condition 3, retention time = 1.87 min LC/MS(ESI ) m/z; 455 [M+H] LC/MS(ESI ) m/z; 453 [M-H] LC/MS: condition 3, retention time = 1.66 min LC/MS(ESI ) m/z; 419 [M+H] H-NMR (CDCl ) δ : 0.90 (s, 3H), 1.81-1.98 (m, 1H), 2.10-2.26 (m, 1H), 2.51-2.69 (m, 1H), 3.18-3.33 (m, 1H), 3.34-3.52 (m, 1H), 3.52-3.69 (m, 1H), 3.69-3.81 (m, 1H), 5.40-5.52 (m, 1H), 6.42 (d, J = 7.8 Hz, 1H), 6.67 (s, 1H), 7.46 (s, 1H), 7.65-7.86 (m, 2H), 33 7.95 (d, J = 7.5 Hz, 1H), 8.05 (d, J =7.2 Hz, 1H), 8.10 (s, 1H), 9.43 (s, 1H), 11.40 (s, 1H).

LC/MS: condition 3, retention time = 2.07 min LC/MS(ESI ) m/z; 491 [M+H] LC/MS(ESI ) m/z; 489 [M-H] LC/MS: condition 3, retention time = 1.89 min 34 LC/MS(ESI ) m/z; 455 [M+H] LC/MS(ESI ) m/z; 453 [M-H] LC/MS: condition 3, retention time = 1.88 min LC/MS(ESI ) m/z; 417 [M+H] LC/MS: condition 1, retention time = 2.57 min 36 LC/MS(ESI ) m/z; 410 [M+H] LC/MS(ESI ) m/z; 408 [M-H] LC/MS: condition 1, retention time = 2.57 min 37 LC/MS(ESI ) m/z; 423 [M+H] LC/MS(ESI ) m/z; 421 [M-H] LC/MS: condition 1, retention time = 3.20 min 38 LC/MS(ESI ) m/z; 379 [M+H] LC/MS(ESI ) m/z; 377 [M-H] TABLE 67 Ex Data LC/MS: condition 1, retention time = 3.00 min 39 LC/MS(ESI ) m/z; 441 [M+H] LC/MS(ESI ) m/z; 439 [M-H] LC/MS: condition 1, retention time = 3.02 min LC/MS(ESI ) m/z; 441 [M+H] LC/MS(ESI ) m/z; 439 [M-H] LC/MS: condition 1, retention time = 3.50 min 41 LC/MS(ESI ) m/z; 441 [M+H] LC/MS(ESI ) m/z; 439 [M-H] LC/MS: condition 1, retention time = 2.40 min 42 LC/MS(ESI ) m/z; 398 [M+H] LC/MS(ESI ) m/z; 396 [M-H] LC/MS: condition 1, retention time = 3.07 min 43 LC/MS(ESI ) m/z; 398 [M+H] LC/MS(ESI ) m/z; 396 [M-H] LC/MS: condition 1, retention time = 1.67 min LC/MS(ESI ) m/z; 398 [M+H] LC/MS(ESI ) m/z; 396 [M-H] LC/MS: condition 3, retention time = 1.84 min LC/MS(ESI ) m/z; 383 [M+H] LC/MS: condition 3, retention time = 1.34 min LC/MS(ESI ) m/z; 405 [M+H] H-NMR (CDCl ) δ : 0.88 (d, J = 7.2 Hz, 3H), 1.33-2.08 (m, 10H), 2.40-2.79 (m, 4H), 2.86-3.12 (m, 2H), 5.38-5.49 (m, 1H), 6.41 (d, J = 8.4 Hz, 1H), 6.80-6.90 (m, 1H), 7.40-7.48 (m, 1H), 8.38 (br s, 1H), 9.48 (s, 1H), 11.33 (s, 1H).

LC/MS: condition 3, retention time = 1.06 min LC/MS(ESI ) m/z; 351 [M+H] H-NMR (CDCl ) δ : 0.83 (s, 9H), 1.04 (d, J = 6.6 Hz, 3H), 1.36-2.17 (m, 12H), 2.70-3.00 (m, 2H), 3.38-3.90 (m, 2H), 4.55-4.85 (m, 1H), .10-5.30 (m, 1H), 6.41 (d, J = 7.8 Hz, 1H), 6.52 (s, 1H), 7.46 (s, 1H), 7.57 (d, J = 8.4 Hz, 1H), 9.46 (s, 1H), 11.74 (br s, 1H).

LC/MS: condition 3, retention time = 2.37 min LC/MS(ESI ) m/z; 449 [M+H] LC/MS: condition 3, retention time = 2.28 min LC/MS(ESI ) m/z; 449 [M+H] LC/MS: condition 3, retention time = 1.22 min LC/MS(ESI ) m/z; 376 [M+H] LC/MS(ESI ) m/z; 374 [M-H] H-NMR (DMSO-d ) δ : 1.79-1.90 (m, 2H), 2.12-2.28 (m, 2H), 2.70-2.90 (m, 2H), 2.90-3.04 (m, 2H), 3.63 (s, 2H), 4.62-4.87 (m, 1H), 6.64 (d, J = 3.6 Hz, 1H), 7.56 (d, J = 8.1 Hz, 2H), 7.61 (d, 50 J = 3.6 Hz, 1H), 7.82 (d, J = 8.4 Hz, 2H), 8.74 (s, 1H).

LC/MS: condition 3, retention time = 1.37 min LC/MS(ESI ) m/z; 401 [M+H] LC/MS(ESI ) m/z; 399 [M-H] TABLE 68 Ex Data H-NMR (DMSO-d ) δ: 1.77-1.93 (m, 2H), 2.08-2.30 (m, 2H), 2.66-2.89 (m, 2H), 2.98-3.14 (m, 2H), 3.69 (s, 2H), 4.60-4.80 (m, 1H), 6.60-6.70 (m, 1H), 6.86 (d, J = 3.6 Hz, 1H), 6.96 (d, J = 3.3 Hz, 1H), 7.61 (d, J = 3.0 Hz, 1H), 8.74 (s, 1H), 12.36 (br s, 1H).

LC/MS: condition 3, retention time = 1.43 min LC/MS(ESI ) m/z; 416, 418 [M+H] LC/MS(ESI ) m/z; 414, 416 [M-H] H-NMR (DMSO-d ) δ: 1.78-1.90 (m, 2H), 2.10-2.28 (m, 2H), 2.70-2.90 (m, 2H), 2,90-3.05 (m, 2H), 3.63 (s, 2H), 4.61-4.79 (m, 1H), 6.65 (d, J = 3.3 Hz, 1H), 7.52-7.64 (m, 3H), 7.71 (d, J = 52 8.1 Hz, 2H), 8.74 (s, 1H).

LC/MS: condition 3, retention time = 1.75 min LC/MS(ESI ) m/z; 444 [M+H] LC/MS(ESI ) m/z; 442 [M-H] LC/MS: condition 3, retention time = 1.79 min LC/MS(ESI ) m/z; 285 [M+H] H-NMR (CDCl ) δ : 2.05-2.48 (m, 6H), 3.10-3.30 (m, 2H), 3.64 (s, 2H), 4.91-5.10 (m, 1H), 6.46 (d, J = 8.3 Hz, 1H), 6.76-6.89 (m, 1H), 7.21-7.41 (m, 5H), 7.42-7.53 (m, 1H), 7.82 (d, J = 8.0 Hz, 1H), 9.44 (s, 1H), 12.1 (s, 1H).

LC/MS: condition 1, retention time = 0.37 min LC/MS(ESI ) m/z; 359 [M+H] H-NMR (DMSO-d ) δ: 1.98-2.22 (m, 4H), 2.30-2.68 (m, 2H), 3.00-3.18 (m, 2H), 3.76 (s, 2H), 4.83-5.02 (m, 1H), 6.19 (d, J = 7.7 Hz, 1H), 6.80 (d, J = 3.6 Hz, 1H), 6.90 (d, J = 3.6 Hz, 1H), 55 6.92-7.03 (m, 1H), 7.60 (d, J = 3.3 Hz, 1H), 8.21 (d, J = 8.0 Hz, 1H), 8.32 (s, 1H), 9.02 (s, 1H).

LC/MS: condition 1, retention time = 0.94 min LC/MS(ESI ) m/z; 399 [M+H] H-NMR (CD OD) δ: 2.12-2.32 (m, 4H), 2.39-2.57 (m, 2H), 3.08-3.23 (m, 2H), 3.75 (s, 2H), 5.09-5.25 (m, 1H), 6.47 (d, J = 8.04 Hz, 1H), 6.95 (d, J = 4.2 Hz, 1H), 7.50-7.70 (m, 5H), 8.28 (d, J = 8.0 Hz, 1H), 9.19 (s, 1H).

LC/MS: condition 1, retention time = 1.65 min LC/MS(ESI ) m/z; 427 [M+H] H-NMR (DMSO-d ) δ: 1.98-2.43 (m, 6H), 2.95-3.09 (m, 2H), 3.69 (s, 2H), 4.86-5.01 (m, 1H), 6.19 (d, J = 8.0 Hz, 1H), 7.81 (d, J = 3.9 Hz, 1H), 7.50-7.68 (m, 3H), 7.83 (d, J = 8.3 Hz, 2H), 8.21 (d, J = 8.9 Hz, 1H), 9.02 (s, 1H).

LC/MS: condition 1, retention time = 0.37 min LC/MS(ESI ) m/z; 384 [M+H] H-NMR (DMSO-d ) δ: 1.97-2.24 (m, 4H), 2.35-2.60 (m, 2H), 2.92-3.11 (m, 2H), 3.73 (s, 2H), 4.85-5.03 (m, 1H), 6.01 (d, J = 8.0 Hz, 1H), 6.81 (d, J = 3.6 Hz, 1H), 6.60 (d, J = 3.6 Hz, 1H), 58 7.64-7.79 (m, 2H), 7.86 (d, J = 9.2 Hz, 1H), 8.20 (d, J = 8.0 Hz, 1H), 8.32 (s, 1H).

LC/MS: condition 1, retention time = 0.45 min LC/MS(ESI ) m/z; 402 [M+H] TABLE 69 Ex Data H-NMR (DMSO-d ) δ : 1.74-1.90 (m, 2H), 1.98-2.19 (m, 2H), 2.70-3.15 (m, 4H), 3.50 (s, 2H), 3.98-4.14 (m, 1H), 4.18 (s, 2H), 6.31(d, J = 3.0 Hz, 1H), 7.18 (br s, 1H), 7.22-7.29 (m, 1H), 7.31-7.38 (m, 5H), 7.4 (br s, 1H), 7.93 (s, 1H).

LC/MS: condition 1, retention time = 0.35 min LC/MS(ESI ) m/z; 362 [M+H] H-NMR (DMSO-d ) δ : 1.80-1.98 (m, 2H), 2.68-3.00 (m, 4H), 3.63-3.60 (m, 2H), 4.11-4.31 (m, 3H), 4.43 (s, 2H), 6.29 (br s, 1H), 7.27 (s, 1H), 7.32-7.50 (m, 5H), 7.95 (s, 1H), 11.7 (s, 1H).

LC/MS: condition 1, retention time = 2.78 min LC/MS(ESI ) m/z; 426 [M+H] H-NMR (DMSO-d ) δ : 1.71-1.90 (m, 2H), 2.00-2.20 (m, 2H), 2.68-3.03 (m, 4H), 3.54 (s, 2H), 3.98-4.26 (m, 3H), 6.31(s, 1H), 7.19 (s, 1H), 7.32-7.49 (m, 2H), 7.68-7.80 (m, 1H), 7.93 (s, 1H), 8.40-8.61 (m, 2H), 11.7 (s, 1H).

LC/MS: condition 1, retention time = 0.33 min LC/MS(ESI ) m/z; 363 [M+H] H-NMR (DMSO-d ) δ : 1.80-1.92 (m, 2H), 2.02-2.20 (m, 2H), 2.68-3.09 (m, 4H), 3.60 (s, 2H), 4.00-4.29 (m, 3H), 6.31 (s, 1H), 7.21 (s, 1H), 7.42 (s, 1H), 7.55 (d, J = 7.7 Hz, 2H), 7.81 (d, J = 7.4 Hz, 2H), 7.94 (s, 1H), 11.7 (s, 1H).

LC/MS: condition 1, retention time = 0.35 min LC/MS(ESI ) m/z; 387 [M+H] H-NMR (DMSO-d ) δ : 1.70-1.92 (m, 2H), 2.01-2.20 (m, 2H), 2.71-3.12 (m, 4H), 3.60 (s, 2H), 4.00-4.33 (m, 3H), 6.32 (d, J = 3.6 Hz, 1H), 7.21 (s, 1H), 7.42 (d, J = 3.6 Hz, 1H), 7.58 (s, 63 J = 7.7 Hz, 2H), 7.71 (d, J = 8.0 Hz, 2H), 7.94 (s, 1H), 11.7 (s, 1H).

LC/MS: condition 1, retention time = 0.64 min LC/MS(ESI ) m/z; 430 [M+H] H-NMR (DMSO-d ) δ : 1.80-2.00 (m, 2H), 2.55-2.79 (m, 2H), 2.85-3.10 (m, 2H), 4.20 (s, 2H), 4.25-4.51 (m, 3H), 6.39 (d, J = 2.4, 1H), 7.24 (s, 1H), 7.43 (s, 1H), 7.95 (s, 1H), 8.94 (s, 1H), 11.7 (s, 1H).

LC/MS: condition 1, retention time = 0.39 min LC/MS(ESI ) m/z; 399 [M+H] H-NMR (CDCl ) δ : 1.95-2.13 (m, 2H), 2.80-3.10 (m, 4H), 3.48-3.62 (m, 2H), 4.02-4.18 (m, 1H), 4.40 (s, 2H), 4.80-4.98 (m, 1H), 5.66 (s, 1H), 6.33-6.51 (m, 1H), 7.15-7.45 (m, 1H), 7.99 (s, 1H), 9.31 (s, 1H).

H-NMR (CDCl ) δ : 1.89-2.00 (m, 2H), 2.11-2.28 (m, 2H), 2.91-3.24 (m, 4H), 3.84 (s, 2H), 4.14-4.30 (m, 1H), 4.39 (s, 2H), 5.32 (s, 1H), 6.45 (d, J = 3.9 Hz, 1H), 7.30 (d, J = 3.9 Hz, 1H), 7.73 (s, 1H), 7.97 (s, 1H), 8.77 (s, 1H), 9.62 (s, 1H).

LC/MS: condition 1, retention time = 0.33 min LC/MS(ESI ) m/z; 369 [M+H] H-NMR (CD OD) δ : 0.90-1.05 (m, 3H), 1.53-2.87 (m, 7H), 3.39-3.53 67 (m, 2H), 4.20-4.56 (m, 3H), 6.48 (d, J = 2.4 Hz, 1H), 7.00-7.35 (m, 5H), 7.67 (s, 1H), 7.90 (s, 1H).

TABLE 70 Ex Data H-NMR (CD OD) δ : 2.11-2.22 (m, 2H), 2.92-3.18 (m, 4H), 3.41-3.52 (m, 2H), 4.33 (d, J = 3.9 Hz, 2H), 4.42-4.65 (m, 1H), 6.44-6.49 68 (m, 1H), 7.36-7.43 (m, 1H), 7.92 (d, J = 4.5 Hz, 1H).

LC/MS: condition 1, retention time = 0.35 min LC/MS(ESI ) m/z; 272 [M+H] LC/MS: condition 3, retention time = 1.22 min LC/MS(ESI ) m/z; 298 [M+H] H-NMR (CDCl ) δ : 1.40-2.10 (m, 4H), 2.15-2.60 (m, 4H), 3.22-3.62 (m, 4H), 4.88-5.21 (m, 1H), 6.45 (d, J = 7.7 Hz, 1H), 6.81 (s, 1H), 7.49 (s, 1H), 7.74 (d, J = 7.7 Hz, 1H), 9.43 (s, 1H), 12.1 (s, 1H).

LC/MS: condition 1, retention time = 2.62 min LC/MS(ESI ) m/z; 298 [M+H] H-NMR (CDCl ) δ : 2.08-2.31 (m, 4H), 2.32-2.53 (m, 2H), 3.12-3.32 (m, 2H), 3.73 (s, 2H), 4.90-5.11 (m 1H), 6.36 (d, J = 3.6 Hz, 1H), 6.46 (d, J = 8.3 Hz, 1H), 6.78 (d, J = 3.9 Hz, 2H), 7.47 (d, J 71 = 3.9 Hz, 1H), 7.79 (d, J = 8.3 Hz, 1H), 9.43 (s, 1H), 11.6 (s, 1H).

LC/MS: condition 1, retention time = 0.89 min LC/MS(ESI ) m/z; 417 [M+H] LC/MS: condition 1, retention time = 0.55 min LC/MS(ESI ) m/z; 394 [M+H] LC/MS: condition 1, retention time = 0.62 min LC/MS(ESI ) m/z; 421 [M+H] H-NMR (CDCl ) δ : 2.02-2.49 (m, 6H), 3.06-3.26 (m, 2H), 3.57 (d, J = 4.5 Hz, 2H), 4.83-5.13 (m, 1H), 5.87 (s, 1H), 6.43 (dd, J = 14.0, 8.0 Hz, 1H), 6.76 (dd, J = 18.8, 3.3Hz, 1H), 7.02-7.35 (m, 74 3H), 7.42-7.56 (m, 1H), 7.79 (dd, J = 12.8, 8.0 Hz, 1H), 11.3 (s, 1H).

LC/MS: condition 1, retention time = 0.40 min LC/MS(ESI ) m/z; 395 [M+H] H-NMR (DMSO-d ) δ: 1.95-2.42 (m, 6H), 2.92-3.10 (m, 2H), 3.61 (s, 2H), 4.86-5.04 (m, 1H), 6.19 (d, J = 7.7 Hz, 1H), 6.81 (d, J = 3.6 Hz, 1H), 7.37 (d, J = 8.9 Hz, 1H), 7.52-7.68 (m, 3H), 8.22 (d, J = 8.3 Hz, 1H), 9.02 (s, 1H).

LC/MS: condition 1, retention time = 2.42 min LC/MS(ESI ) m/z; 427, 428, 429 [M+H] LC/MS: condition 1, retention time = 0.87 min LC/MS(ESI ) m/z; 428 [M+H] H-NMR (CDCl ) δ : 1.79-2.60 (m, 6H), 3.15-3.38 (m, 2H), 3.80 (s, 2H), 4.92-5.17 (m, 1H), 6.46 (d, J = 8.3 Hz, 1H), 6.78 (d, J = 3.6 Hz, 1H), 7.41 (s, 1H), 7.49 (d, J = 3.3 Hz, 1H), 7.79 (d, J = 8.3 Hz, 1H), 9.39 (s, 1H), 12.2 (s, 1H).

LC/MS: condition 1, retention time = 0.37 min LC/MS(ESI ) m/z; 400, 402 [M+H] TABLE 71 H-NMR (DMSO-d ) δ: 1.98-2.70 (m, 6H), 2.92-3.10 (m, 2H), 3.67 (s, 2H), 4.84-5.03 (m, 1H), 6.18 (d, J = 7.7 Hz, 1H), 6.81 (d, J = 3.3 Hz, 1H), 7.43-7.62 (m, 2H), 7.75 (d, J = 6.9 Hz, 2H), 8.22 (d, J = 7.7 Hz, 1H), 9.02 (s, 1H).

LC/MS: condition 1, retention time = 2.49 min LC/MS(ESI ) m/z; 445 [M+H] LC/MS: condition 1, retention time = 0.37 min LC/MS(ESI ) m/z; 410 [M+H] H-NMR (CDCl ) δ : 2.09-2.56 (m, 6H), 3.13-3.36 (m, 2H), 3.66 (s, 2H), 4.90-5.11 (m, 1H), 6.28 (dd, J = 9.5, 3.3 Hz, 2H), 6.40-6.55 (d, J = 8.3 Hz, 1H), 6.78 (d, J = 3.9 Hz, 1H), 7.49 (d, J = 3.6 Hz, 1H), 7.79 (d, J = 8.3 Hz, 1H), 9.41 (s, 1H).

LC/MS: condition 1, retention time = 0.62 min LC/MS(ESI ) m/z; 427, 429 [M+H] H-NMR (CDCl ) δ ： 2.06-2.51 (m, 6H), 3.15-3.33 (m, 2H), 3.80 (s, 2H), 4.90-5.11 (m, 1H), 6.47 (d, J = 8.3 Hz, 1H), 6.79 (d, J = 3.9 Hz, 1H), 6.89 (d, J = 0.9 Hz, 1H), 8.18 (d, J = 1.5 Hz, 1H), 7.47 (d, J = 3.9 Hz, 1H), 7.81 (d, J = 8.3 Hz, 1H), 9.44 (s, 1H).

LC/MS: condition 1, retention time = 0.87 min LC/MS(ESI ) m/z; 443, 445 [M+H] LC/MS: condition 1, retention time = 0.84 min LC/MS(ESI ) m/z; 443, 445 [M+H] H-NMR (CDCl ) δ ： 2.05-2.52 (m, 6H), 3.18-3.30 (m, 2H), 3.82 (s, 2H), 4.93-5.12 (m, 1H), 6.46 (d, J = 7.7 Hz, 1H), 6.78 (d, J = 3.9 Hz, 1H), 7.44 (s, 1H), 7.48 (d, J = 3.9 Hz, 1H), 7.79 (d, J = 8.0 Hz, 1H), 9.42 (s, 1H).

LC/MS: condition 1, retention time = 0.50 min LC/MS(ESI ) m/z; 443, 445 [M+H] H-NMR (CDCl ) δ ： 2.05-2.43 (m, 6H), 3.09-3.25 (m, 2H), 3.60 (s, 2H), 4.91-5.11 (m, 1H), 6.46 (d, J = 8.2 Hz, 1H), 6.80 (d, J = 3.8 Hz, 1H), 6.95-7.11 (m, 2H), 7.15 (s, 1H), 7.46 (d, J = 3.4 Hz, 1H), 7.81 (d, J = 8.2 Hz, 1H), 9.43 (s, 1H).

LC/MS: condition 1, retention time = 1.37 min LC/MS(ESI ) m/z; 439 [M+H] LC/MS: condition 1, retention time = 0.37 min LC/MS(ESI ) m/z; 398 [M+H] LC/MS: condition 1, retention time = 0.35 min LC/MS(ESI ) m/z; 380 [M+H] LC/MS: condition 1, retention time = 3.32 min 87 LC/MS(ESI ) m/z; 413, 415 [M+H] LC/MS(ESI ) m/z; 411, 413 [M-H] TABLE 72 LC/MS: condition 3, retention time = 0.37 min 88 LC/MS(ESI ) m/z; 329 [M+H] LC/MS(ESI ) m/z; 327 [M-H] LC/MS: condition 3, retention time = 1.43 min 89 LC/MS(ESI ) m/z; 460, 462 [M+H] LC/MS(ESI ) m/z; 458, 460 [M-H] LC/MS: condition 3, retention time = 1.33 min LC/MS(ESI ) m/z; 414 [M+H] LC/MS: condition 3, retention time = 0.75 min LC/MS(ESI ) m/z; 340 [M+H] LC/MS: condition 3, retention time = 1.22 min LC/MS(ESI ) m/z; 356 [M+H] LC/MS: condition 3, retention time = 1.03 min LC/MS(ESI ) m/z; 398 [M+H] LC/MS: condition 3, retention time = 1.16 min LC/MS(ESI ) m/z; 325 [M+H] LC/MS: condition 3, retention time = 1.51 min 95 LC/MS(ESI ) m/z; 368 [M+H] LC/MS(ESI ) m/z; 366 [M-H] LC/MS: condition 3, retention time = 0.61 min LC/MS(ESI ) m/z; 367 [M+H] LC/MS: condition 3, retention time = 1.49 min 97 LC/MS(ESI ) m/z; 424 [M+H] LC/MS(ESI ) m/z; 422 [M-H] LC/MS: condition 3, retention time = 0.48 min LC/MS(ESI ) m/z; 353 [M+H] LC/MS(ESI ) m/z; 351 [M-H] LC/MS: condition 3, retention time = 0.85 min LC/MS(ESI ) m/z; 370 [M+H] H-NMR (DMSO-d ) δ : 1.82 (d, J = 11.7 Hz, 2H), 2.18 (t, J = 11.3 Hz, 2H), 2.61-2.78 (m, 6H), 3.05 (d, J = 11.4 Hz, 2H), 4.66 (t, J = 11.7 Hz, 1H), 6.64 (d, J = 3.3 Hz, 1H), 7.60 (d, J = 3.3 Hz, 100 1H), 8.73 (s, 1H), 11.48 (br s, 1H), 12.36 (br s, 1H).

LC/MS: condition 3, retention time = 0.43 min LC/MS(ESI ) m/z; 339 [M+H] LC/MS(ESI ) m/z; 337 [M-H] H-NMR (DMSO-d ) δ : 1.13 (m, 2H), 1.43 (br s, 1H), 1.90 (m, 4H), 2.52 (m, 2H), 3.30 (m, 2H), 4.43 (t, J = 8.1 Hz, 1H), 4.62 (m, 1H), 6.61 (d, J = 3.9 Hz, 1H), 7.60 (d, J = 3.9 Hz, 1H), 8.73 (s, 1H), 11.42 (br s, 1H), 12.34 (br s, 1H).

LC/MS: condition 3, retention time = 1.28 min LC/MS(ESI ) m/z; 315 [M+H] H-NMR (DMSO-d ) δ : 1.10 (m, 2H), 1.45 (br s, 1H), 1.93 (m, 4H), 2.31 (m, 1H), 3.23 (m, 6H), 4.64 (m, 1H), 6.62 (d, J = 3.3 Hz, 1H), 7.60 (d, J = 3.3 Hz, 1H), 8.74 (s, 1H), 11.42 (br s, 1H), 12.35 (br s, 1H).

LC/MS: condition 3, retention time = 1.20 min LC/MS(ESI ) m/z; 396 [M+H] TABLE 73 H-NMR (DMSO-d ) δ: 1.23-1.60 (m, 2H), 1.81-1.92 (m, 4H), 2.16 (br s, 1H), 2.60 (m, 2H), 4.66 (m, 1H), 5.64-5.77 (m, 1H), 103 6.56-6.92 (m, 2H), 7.60 (d, J = 3.6 Hz, 1H), 8.73 (s, 1H).

LC/MS: condition 3, retention time = 1.70 min LC/MS(ESI ) m/z; 336 [M+H] LC/MS: condition 3, retention time = 1.45 min 104 LC/MS(ESI ) m/z; 353 [M+H] LC/MS(ESI ) m/z; 351 [M-H] LC/MS: condition 3, retention time = 1.27 min LC/MS(ESI ) m/z; 353 [M+H] H-NMR (DMSO-d ) δ : 1.43-1.84 (m, 7H), 2.00-2.23 (m, 4H), 2.63-2.77 (m, 2H), 4.57 (br s, 1H), 4.91-4.98 (m, 1H), 6.21 (d, J = 8.3 Hz, 1H), 6.90 (d, J = 3.6 Hz, 1H), 7.58 (d, J = 3.6 Hz, 1H), 8.17 (d, J = 8.3 Hz, 1H), 9.05 (s, 1H), 12.06 (br s, 1H).

LC/MS: condition 3, retention time = 1.39 min LC/MS(ESI ) m/z; 336 [M+H] H-NMR (DMSO-d ) δ : 1.40-1.54 (m, 2H), 1.60-1.84 (m, 5H), 2.03-2.18 (m, 4H), 2.63 (br s, 2H), 4.65 (br s, 1H), 5.06 (br s, 1H), 6.19 (d, J = 8.3 Hz, 1H), 6.85 (s, 1H), 7.57-7.63 (m, 1H), 8.20 (d, J = 8.3 Hz, 1H), 9.03 (s, 1H), 12.26 (br s, 1H).

LC/MS: condition 3, retention time = 1.24 min LC/MS(ESI ) m/z; 336 [M+H] LC/MS: condition 3, retention time = 0.62 min LC/MS(ESI ) m/z; 399 [M+H] LC/MS: condition 3, retention time = 2.16 min LC/MS(ESI ) m/z; 512 [M+H] LC/MS: condition 3, retention time = 0.74 min LC/MS(ESI ) m/z; 383 [M+H] LC/MS: condition 3, retention time = 0.47 min LC/MS(ESI ) m/z; 412 [M+H] H-NMR (DMSO-d ) δ : 1.07 (m, 2H), 1.51 (m, 2H), 1.96 (m, 5H), 2.27 (m, 3H), 2.40 (dd, J = 13.5, 7.8 Hz, 1H), 2.50-2.57 (m, 3H), 2.68 (dd, J = 9.6, 6.3 Hz, 1H), 4.17 (br s, 1H), 4.63, (d, J = 112 1.5 Hz, 2H), 6.62 (d, J = 4.0 Hz, 1H), 7.59 (d, J = 4.0 Hz, 1H), 8.73 (s, 1H), 11.44 (br s, 1H), 12.34 (br s, 1H).

LC/MS: condition 3, retention time = 0.81 min LC/MS(ESI ) m/z; 384 [M+H] H-NMR (DMSO-d ) δ : 1.04 (m, 2H), 1.27 (br s, 1H), 1.86 (d, J = 8.7 Hz, 4H), 2.22 (d, J = 6.9 Hz, 2H), 2.50 (m, 2H), 2.62 (dd, J = 7.5, 6.6 Hz, 2H), 3.48 (dd, J = 7.5, 6.3 Hz, 2H), 4.11 (br 113 s, 1H), 4.58 (m, 1H), 5.18 (br s, 1H), 6.57 (d, J = 3.3 Hz, 1H), 7.56 (d, J = 3.3 Hz, 1H), 8.70 (s, 1H).

LC/MS: condition 3, retention time = 0.74 min LC/MS(ESI ) m/z; 370 [M+H] TABLE 74 H-NMR (DMSO-d ) δ : 1.04 (m, 2H), 1.51 (br s, 1H), 1.90 (m, 4H), 2.30 (d, J = 7.5 Hz, 2H), 2.50 (m, 2H), 2.86 (br s, 4H), 3.14 (br s, 4H), 4.61 (m, 1H), 6.57 (d, J = 3.3 Hz, 1H), 7.56 (d, J = 3.3 Hz, 1H), 8.71 (s, 1H), 11.40 (br s, 1H), 12.32 (br s, 1H).

LC/MS: condition 3, retention time = 1.17 min LC/MS(ESI ) m/z; 432 [M+H] H-NMR (DMSO-d ) δ : 1.18 (m, 2H), 1.56 (br s, 1H), 1.93 (m, 8H), 2.21 (d, J = 7.8 Hz, 2H), 2.50 (m, 6H), 4.64 (m, 1H), 6.62 (d, J = 3.9 Hz, 1H), 7.59 (d, J = 3.9 Hz, 1H), 8.74 (d, J = 2.7 Hz, 1H), 11.39 (br s, 1H), 12.35 (br s, 1H).

LC/MS: condition 3, retention time = 1.19 min LC/MS(ESI ) m/z; 418 [M+H] H-NMR (DMSO-d ) δ : 1.09 (m, 2H), 1.53 (br s, 1H), 1.90 (d, J = 12.0 Hz, 2H), 2.01 (d, J = 12.0 Hz, 2H), 2.33 (d, J = 7.2 Hz, 2H), 2.55 (m, 2H), 2.61 (m, 4H), 2.76 (m, 4H), 4.64 (m, 1H), 6.62 116 (d, J = 3.6 Hz, 1H), 7.60 (d, J = 3.6 Hz, 1H), 8.75 (s, 1H), 11.33 (br s, 1H), 12.34 (br s, 1H).

LC/MS: condition 3, retention time = 1.62 min LC/MS(ESI ) m/z; 420 [M+H] H-NMR (DMSO-d ) δ : 0.09 (m, 2H), 0.39 (m, 2H), 0.87 (m, 1H), 1.11 (m, 2H), 1.45 (br s, 1H), 1.92 (m, 4H), 2.40 (d, J = 6.6 Hz, 2H), 2.43 (d, J = 6.6 Hz, 2H), 2.51 (m, 3H), 4.64 (m, 1H), 6.61 117 (d, J = 3.9 Hz, 1H), 7.59 (d, J = 3.3 Hz, 1H), 8.73 (s, 1H), 11.40 (br s, 1H), 12.32 (br s, 1H).

LC/MS: condition 3, retention time = 1.23 min LC/MS(ESI ) m/z; 368 [M+H] H-NMR (DMSO-d ) δ : 1.09 (m, 2H), 1.52 (br s, 1H), 1.93 (m, 4H), 2.29 (m, 4H), 2.58-2.68 (m, 7H), 4.64 (m, 1H), 6.61 (d, J = 3.6 Hz, 1H), 7.58 (d, J = 3.6 Hz, 1H), 8.74 (s, 1H), 11.31 (br s, 1H), 12.32 (br s, 1H).

LC/MS: condition 3, retention time = 0.97 min LC/MS(ESI ) m/z; 393 [M+H] H-NMR (DMSO-d ) δ : 1.04 (m, 2H), 1.16 (s, 6H), 1.28 (br s, 1H), 1.89 (m, 4H), 2.24 (d, J = 5.4 Hz, 2H), 2.51 (m, 2H), 2.84 (m, 4H), 4.61 (m, 1H), 6.59 (d, J = 3.3 Hz, 1H), 7.59 (d, J = 3.3 Hz, 1H), 8.73 (s, 1H), 11.42 (br s, 1H), 12.34 (br s, 1H).

LC/MS: condition 3, retention time = 1.23 min LC/MS(ESI ) m/z; 382 [M+H] H-NMR (DMSO-d ) δ : 1.05 (m, 2H), 1.51 (br s, 1H), 1.92 (m, 4H), 2.18 (m, 5H), 2.39 (t, J = 6.3 Hz, 2H), 2.55 (m, 2H), 3.47 (dd, J = 12.0, 5.4 Hz, 2H), 4.28 (t, J = 5.4 Hz, 1H), 4.64 (m, 1H), 120 6.62 (d, J = 3.6 Hz, 1H), 7.59 (d, J = 3.6 Hz, 1H), 8.73 (s, 1H), 11.37 (br s, 1H), 12.34 (br s, 1H).

LC/MS: condition 3, retention time = 0.75 min LC/MS(ESI ) m/z; 372 [M+H] TABLE 75 H-NMR (DMSO-d ) δ : 0.99 (m, 2H), 1.56 (br s, 1H), 1.89 (d, J = 10.8 Hz, 2H), 2.00 (d, J = 10.8 Hz, 2H), 2.30 (d, J = 3.9 Hz, 2H), 2.60 (m, 4H), 3.47 (dd, J = 12.0, 6.6 Hz, 2H), 3.59 (s, 2H), 4.31 (t, J = 5.4 Hz, 1H), 4.61 (m, 1H), 6.58 (d, J = 3.6 Hz, 1H), 7.21-7.35 (m, 5H), 7.57 (d, J = 3.6 Hz, 1H), 8.73 (s, 1H), 11.41 (br s, 1H), 12.33 (br s, 1H).

LC/MS: condition 3, retention time = 1.14 min LC/MS(ESI ) m/z; 448 [M+H] H-NMR (DMSO-d ) δ : 0.85 (s, 2H), 0.92 (s, 2H), 1.13 (m, 2H), 1.28 (br s, 1H), 1.90 (m, 4H), 2.26 (m, 1H), 2.56 (m, 4H), 4.61 (m, 1H), 6.61 (d, J = 3.6 Hz, 1H), 7.59 (d, J = 3.6 Hz, 1H), 8.73 (s, 1H), 11.45 (br s, 1H), 12.32 (br s, 1H).

LC/MS: condition 3, retention time = 1.88 min LC/MS(ESI ) m/z; 422 [M+H] H-NMR (DMSO-d ) δ : 1.09 (m, 2H), 1.46 (br s, 1H), 1.92 (m, 4H), 2.35-2.43 (m, 9H), 2.60 (m, 4H), 3.56 (m, 4H), 4.63 (m, 1H), 6.61 (d, J = 3.6 Hz, 1H), 7.59 (d, J = 3.6 Hz, 1H), 8.73 (s, 1H).

LC/MS: condition 3, retention time = 1.40 min LC/MS(ESI ) m/z; 427 [M+H] LC/MS: condition 3, retention time = 1.05 min LC/MS(ESI ) m/z; 393 [M+H] H-NMR (DMSO-d ) δ : 0.04 (t, J = 4.2 Hz, 1H), 0.35 (dd, J = 7.2, 4.2 Hz, 1H), 0.98 (s, 3H), 1.11 (s, 3H), 1.13 (m, 2H), 1.46 (br s, 1H), 1.82 (dd, J = 7.2, 3.6 Hz, 1H), 1.93 (m, 5H), 2.41 (m, 2H), 2.55 (m, 2H), 4.64 (m, 1H), 6.62 (d, J = 3.6 Hz, 1H), 7.59 (d, J = 3.6 Hz, 1H), 8.73 (s, 1H), 11.37 (br s, 1H), 12.34 (br s, 1H).

LC/MS: condition 3, retention time = 1.37 min LC/MS(ESI ) m/z; 382 [M+H] H-NMR (DMSO-d ) δ: 1.05-1.27 (m, 3H), 1.36-1.58 (m, 6H), 1.94 (m, 4H), 2.41 (s, 1H), 2.42 (d, J = 6.6 Hz, 2H), 2.55 (m, 6H), 3.93 (br s, 2H), 4.65 (m, 2H), 6.63 (d, J = 3.6 Hz, 1H), 7.60 (d, J = 3.6 Hz, 1H), 8.73 (s, 1H).

LC/MS: condition 3, retention time = 1.35 min LC/MS(ESI ) m/z; 426 [M+H] H-NMR (DMSO-d ) δ : 1.16 (m, 2H), 1.48 (br s, 1H), 1.92 (m, 4H), 2.55 (m, 5H), 3.61 (d, J = 6.0 Hz, 2H), 4.65 (m, 1H), 6.62 (d, J = 3.6 Hz, 1H), 7.59 (d, J = 3.6 Hz, 1H), 8.73 (s, 1H), 11.34 (br s, 1H), 12.34 (br s, 1H).

LC/MS: condition 3, retention time = 1.02 min LC/MS(ESI ) m/z; 353 [M+H] H-NMR (DMSO-d ) δ : 1.07 (m, 2H), 1.47 (m, 2H), 1.56 (br s, 1H), 1.78 (d, J = 17.4 Hz, 2H), 1.95 (m, 6H), 2.15 (d, J = 6.9 Hz, 2H), 2.21 (m, 1H), 2.55 (m, 2H), 2.92 (d, J = 17.4 Hz, 2H), 4.64 (m, 128 1H), 6.62 (d, J = 3.6 Hz, 1H), 7.59 (d, J = 3.6 Hz, 1H), 8.73 (s, 1H), 11.42 (br s, 1H), 12.34 (br s, 1H).

LC/MS: condition 3, retention time = 1.36 min LC/MS(ESI ) m/z; 450 [M+H] TABLE 76 H-NMR (DMSO-d ) δ : 1.10 (m, 2H), 1.34 (br s, 1H), 1.89 (m, 4H), 2.35 (d, J = 6.6 Hz, 2H), 2.55 (m, 2H), 3.11 (d, J = 8.4 Hz, 2H), 3.53 (d, J = 8.4 Hz, 2H), 4.61 (m, 1H), 6.60 (d, J = 3.6 Hz, 1H), 6.82 (s, 1H), 7.59 (d, J = 3.6 Hz, 1H), 8.70 (s, 1H), 11.37 (br s, 1H), 12.34 (br s, 1H).

LC/MS: condition 3, retention time = 1.20 min LC/MS(ESI ) m/z; 438 [M+H] LC/MS(ESI ) m/z; 436 [M-H] H-NMR (DMSO-d ) δ : 1.09 (m, 2H), 1.51 (m, 2H), 1.74-1.84 (m, 4H), 1.92 (m, 4H), 2.43 (d, J = 6.6 Hz, 2H), 2.55 (m, 4H), 3.59 (ddd, J = 14.4, 7.8, 1.2 Hz, 1H), 3.72 (ddd, J = 14.4, 7.8, 1.2 130 Hz, 1H), 3.85 (m, 1H), 4.64 (m, 1H), 6.62 (d, J = 3.6 Hz, 1H), 7.59 (d, J = 3.6 Hz, 1H), 8.73 (s, 1H).

LC/MS: condition 3, retention time = 1.21 min LC/MS(ESI ) m/z; 398 [M+H] LC/MS: condition 3, retention time = 1.10 min LC/MS(ESI ) m/z; 372 [M+H] LC/MS: condition 3, retention time = 1.25 min 132 LC/MS(ESI ) m/z; 503 [M+H] LC/MS(ESI ) m/z; 501 [M-H] LC/MS: condition 3, retention time = 1.39 min LC/MS(ESI ) m/z; 313 [M+H] H-NMR (DMSO-d ) δ : 1.19 (m, 2H), 1.42 (br s, 1H), 1.56 (dd, J = 14.1, 7.5 Hz, 2H), 1.80 (m, 2H), 1.92 (m, 4H), 2.55 (m, 2H), 4.64 (m, 1H), 6.62 (d, J = 3.6 Hz, 1H), 7.59 (d, J = 3.6 Hz, 1H), 8.73 (s, 1H).

LC/MS: condition 3, retention time = 1.66 min LC/MS(ESI ) m/z; 338 [M+H] LC/MS: condition 3, retention time = 1.80 min 135 LC/MS(ESI ) m/z; 463 [M+H] LC/MS(ESI ) m/z; 461 [M-H] LC/MS: condition 3, retention time = 1.85 min 136 LC/MS(ESI ) m/z; 410 [M+H] LC/MS(ESI ) m/z; 408 [M-H] LC/MS: condition 3, retention time = 2.13 min 137 LC/MS(ESI ) m/z; 324 [M+H] LC/MS(ESI ) m/z; 322 [M-H] LC/MS: condition 3, retention time = 2.13 min 138 LC/MS(ESI ) m/z; 299 [M+H] LC/MS(ESI ) m/z; 297 [M-H] LC/MS: condition 3, retention time = 2.49 min 139 LC/MS(ESI ) m/z; 367 [M+H] LC/MS(ESI ) m/z; 365 [M-H] LC/MS: condition 3, retention time = 1.86 min 140 LC/MS(ESI ) m/z; 329 [M+H] LC/MS(ESI ) m/z; 327 [M-H] TABLE 77 LC/MS: condition 3, retention time = 1.93 min 141 LC/MS(ESI ) m/z; 343 [M+H] LC/MS(ESI ) m/z; 341 [M-H] LC/MS: condition 3, retention time = 1.61 min LC/MS(ESI ) m/z; 398 [M+H] LC/MS(ESI ) m/z; 396 [M-H] LC/MS: condition 3, retention time = 2.13 min 143 LC/MS(ESI ) m/z; 329 [M+H] LC/MS(ESI ) m/z; 327 [M-H] LC/MS: condition 3, retention time = 2.45 min 144 LC/MS(ESI ) m/z; 359 [M+H] LC/MS(ESI ) m/z; 357 [M-H] LC/MS: condition 3, retention time = 2.19 min 145 LC/MS(ESI ) m/z; 343 [M+H] LC/MS(ESI ) m/z; 341 [M-H] LC/MS: condition 3, retention time = 2.26 min 146 LC/MS(ESI ) m/z; 338 [M+H] LC/MS(ESI ) m/z; 336 [M-H] LC/MS: condition 3, retention time = 2.41 min 147 LC/MS(ESI ) m/z; 345 [M+H] LC/MS(ESI ) m/z; 343 [M-H] LC/MS: condition 3, retention time = 2.83 min LC/MS(ESI ) m/z; 353 [M+H] LC/MS(ESI ) m/z; 351 [M-H] LC/MS: condition 3, retention time = 2.58 min LC/MS(ESI ) m/z; 339 [M+H] LC/MS: condition 3, retention time = 2.31 min 150 LC/MS(ESI ) m/z; 369 [M+H] LC/MS(ESI ) m/z; 367 [M-H] LC/MS: condition 3, retention time = 1.95 min 151 LC/MS(ESI ) m/z; 387 [M+H] LC/MS(ESI ) m/z; 385 [M-H] LC/MS: condition 3, retention time = 1.94 min LC/MS(ESI ) m/z; 370 [M+H] LC/MS: condition 3, retention time = 1.62 min 153 LC/MS(ESI ) m/z; 356 [M+H] LC/MS(ESI ) m/z; 354 [M-H] LC/MS: condition 3, retention time = 1.64 min LC/MS(ESI ) m/z; 368 [M+H] LC/MS: condition 3, retention time = 2.07 min LC/MS(ESI ) m/z; 506 [M+H] LC/MS(ESI ) m/z; 504 [M-H] Pharmacological assay Now, a pharmacological assay of the tricyclic pyridine compounds of the present invention will be described.

After addition of a termination reagent containing EDTA (ehylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS. From the plot of logarithm of a compound concentration and inhibitory activity, the IC was calculated. The results of JAK3, JAK1, JAK2 and Tyk2 enzyme assays of the compounds of Synthetic Examples are shown in Tables 78 to 81. “*” in the Tables indicates IC > 1 µM.

TABLE 78 Ex .

TABLE 79 Ex .

TABLE 80 Ex .

TABLE 81 Ex .

The tricyclic pyridine compounds of the present invention have favorable inhibitory activity against JAKs as shown above.

ASSAY EXAMPLE 3. Inhibition of proliferation of erythro-leukemic cell line The inhibitory activity of the tricyclic pyridine compounds of the present invention on cell proliferation mediated by JAK signal can be assayed using a human erythro- leukemic cell line, TF-1.

Cell proliferation can be assayed using WST-8 reagent (Kishida Chemical Co., Ltd.) according to instructions by the manufacturer. The formazan pigment is generated by the addition of WST-8 reagent solution to each well of the culture plates and the subsequent incubation in a CO incubator (5% CO , 37°C) for 4 hours, and then detected by measuring the absorbance at 450 nm with a microplate reader. From the plot of logarithm of the compound concentrations and the inhibitory activities, the IC value can be calculated.

Now, examples of formulations of tricyclic pyrimidine compounds represented by the formula (I ) and tricyclic pyridine compounds represented by the formula (I ) of the present invention (hereinafter referred to collectively as compounds represented by the formula (I)) will be shown.

FORMULATION EXAMPLE 1 A granule preparation containing the following ingredients is prepared.

Ingredients Compound represented by the formula (I) 10 mg Lactose 700 mg Corn Starch 274 mg HPC-L 16 mg Total 1000 mg A compound represented by the formula (I) and lactose are sifted through a 60- mesh sieve. Corn starch is sifted though a 120-mesh sieve. They are mixed in a V- type blender. The powder mixture is kneaded with a low-viscosity hydroxypropylcellulose (HPC-L) aqueous solution, granulated (extrusion granulation, die size 0.5-1 mm) and dried. The resulting dry granules are sifted through a shaking sieve (12/60 mesh) to obtain a granule preparation. 40 FORMULATION EXAMPLE 2 A powder preparation for capsulation containing the following ingredients is prepared.

Ingredients Compound represented by the formula (I) 10 mg Lactose 79 mg Corn Starch 10 mg Magnesium Stearate 1 mg Total 100 mg A compound represented by the formula (I) and lactose are sifted through a 60- mesh sieve. Corn starch is sifted though a 120-mesh sieve. They are mixed with magnesium stearate in a V-type blender. The 10% powder is put in hard gelatin capsules No. 5, 100 mg each.

FORMULATION EXAMPLE 3 A granule preparation for capsulation containing the following ingredients is prepared.

Ingredients Compound represented by the formula (1) 15 mg Lactose 90 mg Corn Starch 42 mg HPC-L 3 mg Total 150 mg A compound represented by the formula (I) and lactose are sifted through a 60- mesh sieve. Corn starch is sifted though a 120-mesh sieve. They are mixed in a V- type blender. The powder mixture is kneaded with a low-viscosity hydroxypropylcellulose (HPC-L) aqueous solution, granulated and dried. The resulting dry granules are sifted through a shaking sieve (12/60 mesh). The granules are put in hard gelatin capsules No. 4, 150 mg each.

FORMULATION EXAMPLE 4 A tablet preparation containing the following ingredients is prepared.

Ingredients Compound represented by the formula (I) 10 mg Lactose 90 mg Microcrystalline cellulose 30 mg Magnesium Stearate 5 mg CMC-Na 15 mg Total 150 mg A compound represented by the formula (I), lactose, microcrystalline cellulose and CMC-Na (carboxymethylcellulose sodium salt) are sifted through a 60-mesh sieve and mixed. The powder mixture is mixed with magnesium stearate to give a bulk powder mixture. The powder mixture is compressed directly into 150 mg tablets.

FORMULATION EXAMPLE 5 An intravenous preparation is prepared as follows.

Compound represented by the formula (I) 100 mg Saturated Fatty Acid Glyceride 1000 ml Solutions having the above-mentioned composition are usually administered to a patient intravenously at a rate of 1 ml per 1 minute.

INDUSTRIAL APPLICABILITY The compounds of the present invention have excellent JAK inhibitory activities and are useful for prevention or treatment of autoimmune diseases, especially rheumatoid arthritis, inflammatory diseases and allergic diseases.

Claims

WHAT WE CLAIM IS:

1. A compound represented by the formula (I ): 1b b (R ) b ( I ) [wherein the ring A is represented by the formula (II ): (II ) 1b 4b 5b 17b 1b (wherein T is CR R , C(=O), C(=S), C(=NR ), a sulfur atom, S(=O) or S(=O) , U 6b 1b 8b b is a nitrogen atom or CR , and W is a nitrogen atom or CR ), the formula (III ): (III ) 2b 4b 2b 6b 2b 8b 9b (wherein T is CR , U is a nitrogen atom or CR , and W is CR R , C(=O), C(=S), 17b 10b 10 C(=NR ), NR , an oxygen atom, a sulfur atom, S(=O) or S(=O) (provided that when 2b 6b 2b b U is CR , W is not C(=O))) or the formula (IV ): 3b (IV ) 3b 4b 5b 17b 3b (wherein T is CR R , C(=O), C(=S), C(=NR ), a sulfur atom, S(=O) or S(=O) , U 6b 7b 17b 10b is CR R , C(=O), C(=S), C(=NR ), NR , an oxygen atom, a sulfur atom, S(=O) or 3b 8b 9b 17b 11b 15 S(=O) , and W is CR R , C(=O), C(=S), C(=NR ), NR , an oxygen atom, a sulfur 3b 4b 5b 3b 6b 7b 3b atom, S(=O) or S(=O) (provided that when T is CR R and U is CR R , W is 8b 9b not CR R )), b 15b X is a nitrogen atom or CR , b 16b Y is CR , 20 R is a hydrogen atom, a halogen atom, a C alkyl group or a C haloalkyl group, 1-6 1-6 the ring B is a C cycloalkane, a C cycloalkene, a 3 to 11-membered non-aromatic 3-11 3-11 heterocycle, a C aromatic carbocycle or a 5 to 10-membered aromatic heterocycle, 6-14 L is a single bond, a C alkylene group, a C alkenylene group or a C alkynylene 1-6 2-6 2-6 group (the C alkylene group, the C alkenylene group and the C alkynylene group 1-6 2-6 2-6 25 are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, amino groups, cyano groups and nitro groups), L is a single bond, a C alkylene group, a C alkenylene group or a C alkynylene 1-6 2-6 2-6 group (the C alkylene group, the C alkenylene group and the C alkynylene group 1-6 2-6 2-6 5 are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, amino groups, cyano groups and nitro groups), 3b b b L is a single bond or represented by any of the following formulae (V -1) to (V -20): 12b 1b b b R E ( V -1 ) ( V -2 ) b b b b (V -3 ) (V -4 ) ( V -5 ) ( V -6 ) 1b 13b b b b b b ( V -7 ) (V -8 ) (V -9 ) (V -10 ) ( V -11 ) ( V ) 1b 1b O N N N 12b 12b 13b R R R b b b b b (V -12 ) (V -13 ) ( V -14 ) ( V -15 ) (V -16 ) 1b 14b 1b 1b O N N O N N 12b 12b 13b 12b 13b R R R R R b b b b (V -17 ) ( V -18 ) (V -19 ) (V -20 ) 1b 18b 10 (wherein E is an oxygen atom, a sulfur atom or NR ), 3b 2b when L is a single bond, R is a hydrogen atom, a halogen atom, a C cycloalkyl 3-11 group, a 3 to 14-membered non-aromatic heterocyclyl group, a C aryl group, a 5 to 6-14 10-membered aromatic heterocyclyl group, a 8 to 14-membered partially saturated aromatic cyclic group or a 8 to 14-membered aromatic ring-condensed alicyclic 15 hydrocarbon group (the C cycloalkyl group, the 3 to 14-membered non-aromatic 3-11 heterocyclyl group, the C aryl group, the 5 to 10-membered aromatic heterocyclyl 6-14 group, the 8 to 14-membered partially saturated aromatic cyclic group and the 8 to 14- membered aromatic ring-condensed alicyclic hydrocarbon group are unsubstituted or substituted with one or more identical or different substituents independently selected 4b 9b 20 from the substituent set V and the substituent set V ), 3b 2b when L is not a single bond, R is a hydrogen atom, a C alkyl group, a C alkenyl 1-6 2-6 group (the C alkyl group and the C alkenyl group are unsubstituted or substituted 1-6 2-6 with one or more identical or different substituents independently selected from the 6b 9b substituent set V and the substituent set V ), a C cycloalkyl group, a 3 to 14- 3-11 membered non-aromatic heterocyclyl group, a C aryl group, a 5 to 10-membered 6-14 aromatic heterocyclyl group, a 8 to 14-membered partially saturated aromatic cyclic group or a 8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon group (the 5 C cycloalkyl group, the 3 to 14-membered non-aromatic heterocyclyl group, the C 3-11 6-14 aryl group, the 5 to 10-membered aromatic heterocyclyl group, the 8 to 14-membered partially saturated aromatic cyclic group and the 8 to 14-membered aromatic ring- condensed alicyclic hydrocarbon group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set 4b 9b 10 V and substituent set V ), n is 0, 1 or 2, R is a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a sulfamoyl group, a phosphono group, a phosphonooxy group, a sulfo group, a sulfoxy group, a tetrazolyl group, a halogen atom, a cyano group, a nitro group, a C alkyl 15 group, a C haloalkyl group, a C cycloalkyl group, a C alkenyl group, a C 1-6 3-11 2-6 2-6 haloalkenyl group, a C alkoxy group, a C haloalkoxy group, a C alkylthio group, a 1-6 1-6 1-6 C haloalkylthio group, a C alkylcarbonyl group, a C haloalkylcarbonyl group, a C 1-6 1-6 1-6 1- alkylsulfonyl group, a C haloalkylsulfonyl group, a C alkoxycarbonyl group, a 6 1-6 1-6 mono-C alkylamino group, a di-C alkylamino group, a mono-C 1-6 1-6 1-6 20 alkylaminocarbonyl group, a di-C alkylaminocarbonyl group or a C 1-6 1-6 b 3b alkylcarbonylamino group (when n is 2, R ’s may be identical or different), 4b 5b 6b 7b 8b 9b each of R , R , R , R , R and R is independently a hydrogen atom, a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a tetrazolyl group, a halogen atom, a cyano group, a C alkyl group, a C alkenyl group, a C alkoxy 1-6 2-6 1-6 25 group, a C alkylthio group, a C alkylcarbonyl group, a C alkylsulfonyl group, a 1-6 1-6 1-6 mono-C alkylamino group, a di-C alkylamino group (the C alkyl group, the C 1-6 1-6 1-6 2-6 alkenyl group, the C alkoxy group, the C alkylthio group, the C alkylcarbonyl 1-6 1-6 1-6 group, the C alkylsulfonyl group, the mono-C alkylamino group and the di-C 1-6 1-6 1-6 alkylamino group are unsubstituted or substituted with one or more identical or different 30 substituents independently selected from the substituent set V ), a C alkoxycarbonyl group, a C cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a 3-11 C aryl group or a 5 to 10-membered aromatic heterocyclyl group (the C cycloalkyl 6-14 3-11 group, the 3 to 11-membered non-aromatic heterocyclyl group, the C aryl group and 6-14 the 5 to 10-membered aromatic heterocyclyl group are unsubstituted or substituted with 35 one or more identical or different substituents independently selected from the substituent set V ), 10b 11b each of R and R is independently a hydrogen atom, a C alkyl group, a C 1-6 2-6 alkenyl group, a C alkylcarbonyl group, a C alkylsulfonyl group, a C 1-6 1-6 1-6 alkoxycarbonyl group, a mono-C alkylaminocarbonyl group, a di-C 1-6 1-6 40 alkylaminocarbonyl group (the C alkyl group, the C alkenyl group, the C 1-6 2-6 1-6 alkylcarbonyl group, the C alkylsulfonyl group, the C alkoxycarbonyl group, the 1-6 1-6 mono-C alkylaminocarbonyl group and the di-C alkylaminocarbonyl group are 1-6 1-6 unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a C cycloalkyl group, a 3 to 11- 3-11 45 membered non-aromatic heterocyclyl group, a C aryl group or a 5 to 10-membered 6-14 aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11-membered non- 3-11 aromatic heterocyclyl group, the C aryl group and the 5 to 10-membered aromatic 6-14 heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), 12b 13b 14b each of R , R and R is independently a hydrogen atom, a C alkyl group or a C 1-6 1- haloalkyl group (the C alkyl group and the C haloalkyl group are unsubstituted or 6 1-6 1-6 5 substituted with one or more identical or different substituents independently selected 3b 8b 9b from the substituent set V , the substituent set V and the substituent set V ), 15b 16b each of R and R is independently a hydrogen atom, a halogen atom, a cyano group, a carbamoyl group, a C alkyl group, a C haloalkyl group, a C cycloalkyl 1-6 1-6 3-11 group, a C alkoxy group, a C haloalkoxy group, a C alkylthio group, a C 1-6 1-6 1-6 1-6 10 alkylcarbonyl group, a C alkylsulfonyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a C aryl group or a 5 to 10-membered aromatic heterocyclyl 6-14 group, 17b 18b each of R and R is independently a hydrogen atom, a hydroxy group, a cyano group, a nitro group, a C alkyl group or a C alkoxy group, 1-6 1-6 15 the substituent set V consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C alkyl groups, C haloalkyl groups, C cycloalkyl groups, C alkenyl groups, C 1-6 1-6 3-11 2-6 2-6 haloalkenyl groups, C alkoxy groups, C haloalkoxy groups, C alkylthio groups, C 1-6 1-6 1-6 1- 20 haloalkylthio groups, C alkylcarbonyl groups, C haloalkylcarbonyl groups, C 6 1-6 1-6 1-6 alkylsulfonyl groups, C haloalkylsulfonyl groups, C alkoxycarbonyl groups, 3 to 11- 1-6 1-6 membered non-aromatic heterocyclyl groups, mono-C alkylamino groups, di-C 1-6 1-6 alkylamino groups, mono-C alkylaminocarbonyl groups, di-C alkylaminocarbonyl 1-6 1-6 groups and C alkylcarbonylamino groups, 2b 1b 25 the substituent set V consists of the groups in the substituent set V , and C aryl 6-14 groups and 5 to 10-membered aromatic heterocyclyl groups (the C aryl groups and 6-14 the 5 to 10-membered aromatic heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), 30 the substituent set V consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C alkoxy groups, C haloalkoxy groups, C alkylthio groups, C haloalkylthio 1-6 1-6 1-6 1-6 groups, C alkylcarbonyl groups, C haloalkylcarbonyl groups, C alkylsulfonyl 1-6 1-6 1-6 35 groups, C haloalkylsulfonyl groups, C alkoxycarbonyl groups, mono-C alkylamino 1-6 1-6 1-6 groups, di-C alkylamino groups, mono-C alkylaminocarbonyl groups, di-C 1-6 1-6 1-6 alkylaminocarbonyl groups, C alkylcarbonylamino groups, C cycloalkyl groups, 3 to 1-6 3-11 11-membered non-aromatic heterocyclyl groups, C aryl group and 5 to 10-membered 6-14 aromatic heterocyclyl groups (the C cycloalkyl groups, the 3 to 11-membered non- 3-11 40 aromatic heterocyclyl groups, the C aryl groups and the 5 to 10-membered aromatic 6-14 heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), the substituent set V consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo 45 groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C alkyl groups, C alkenyl groups, C alkoxy groups, C alkylthio groups, C 1-6 2-6 1-6 1-6 1-6 alkylcarbonyl groups, C alkylsulfonyl groups, C alkoxycarbonyl groups, mono-C 1-6 1-6 1-6 alkylamino groups, di-C alkylamino groups, mono-C alkylaminocarbonyl groups, di- 1-6 1-6 C alkylaminocarbonyl groups, C alkylcarbonylamino groups (the C alkyl groups, 1-6 1-6 1-6 the C alkenyl groups, the C alkoxy groups, the C alkylthio groups, the C 2-6 1-6 1-6 1-6 alkylcarbonyl groups, the C alkylsulfonyl groups, the C alkoxycarbonyl groups, the 1-6 1-6 5 mono-C alkylamino groups, the di-C alkylamino groups, the mono-C 1-6 1-6 1-6 alkylaminocarbonyl groups, the di-C alkylaminocarbonyl groups and the C 1-6 1-6 alkylcarbonylamino groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), C 3-11 cycloalkyl groups, 3 to 11-membered non-aromatic heterocyclyl groups, C aryl 6-14 10 groups and 5 to 10-membered aromatic heterocyclyl groups (the C cycloalkyl groups, 3-11 the 3 to 11-membered non-aromatic heterocyclyl groups, the C aryl groups and the 5 6-14 to 10-membered aromatic heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), 15 the substituent set V consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C alkoxy groups, C alkylthio groups, C alkylcarbonyl groups, C alkylsulfonyl 1-6 1-6 1-6 1-6 groups, C alkoxycarbonyl groups, mono-C alkylamino groups, di-C alkylamino 1-6 1-6 1-6 20 groups, mono-C alkylaminocarbonyl groups, di-C alkylaminocarbonyl groups, C 1-6 1-6 1-6 alkylcarbonylamino groups, C cycloalkyl groups, 3 to 11-membered non-aromatic 3-11 heterocyclyl groups, C aryl groups and 5 to 10-membered aromatic heterocyclyl 6-14 groups (the C alkoxy groups, the C alkylthio groups, the C alkylcarbonyl groups, 1-6 1-6 1-6 the C alkylsulfonyl groups, the C alkoxycarbonyl groups, the mono-C alkylamino 1-6 1-6 1-6 25 groups, the di-C alkylamino groups, the mono-C alkylaminocarbonyl groups, the di- 1-6 1-6 C alkylaminocarbonyl groups, the C alkylcarbonylamino groups, the C cycloalkyl 1-6 1-6 3-11 groups, the 3 to 11-membered non-aromatic heterocyclyl groups, the C aryl groups 6-14 and the 5 to 10-membered aromatic heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected 30 from the substituent set V ), the substituent set V consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C alkoxy groups, C alkylthio groups, C alkylcarbonyl groups, C alkylsulfonyl 1-6 1-6 1-6 1-6 35 groups, C alkoxycarbonyl groups, mono-C alkylamino groups, di-C alkylamino 1-6 1-6 1-6 groups, mono-C alkylaminocarbonyl groups, di-C alkylaminocarbonyl groups, C 1-6 1-6 1-6 alkylcarbonylamino groups (the C alkoxy groups, the C alkylthio groups, the C 1-6 1-6 1-6 alkylcarbonyl groups, the C alkylsulfonyl groups, the C alkoxycarbonyl groups, the 1-6 1-6 mono-C alkylamino groups, the di-C alkylamino groups, the mono-C 1-6 1-6 1-6 40 alkylaminocarbonyl groups, the di-C alkylaminocarbonyl groups and the C 1-6 1-6 alkylcarbonylamino groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), C 3-11 cycloalkyl groups, 3 to 11-membered non-aromatic heterocyclyl groups, C aryl 6-14 groups, 5 to 10-membered aromatic heterocyclyl groups, 8 to 14-membered partially 45 saturated aromatic cyclic groups and 8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon groups (the C cycloalkyl groups, the 3 to 11-membered non- 3-11 aromatic heterocyclyl groups, the C aryl groups, the 5 to 10-membered aromatic 6-14 heterocyclyl groups, the 8 to 14-membered partially saturated aromatic cyclic groups and the 8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon groups are unsubstituted or substituted with one or more identical or different substituents 4b 9b independently selected from the substituent set V and the substituent set V ), and 5 the substituent set V consists of 8 to 14-membered partially saturated aromatic cyclic groups and 8 to 14-membered aromatic ring-condensed alicyclic hydrocarbon groups (the 8 to 14-membered partially saturated aromatic cyclic groups and the 8 to 14- membered aromatic ring-condensed alicyclic hydrocarbon groups are unsubstituted or substituted with one or more identical or different substituents independently selected 10 from the substituent set V ), the substituent set V consists of, mono-C alkylaminosulfonyl groups, di-C 1-6 1-6 alkylaminosulfonyl groups, C alkylsulfonylamino groups (the mono-C 1-6 1-6 alkylaminosulfonyl groups, di-C alkylaminosulfonyl groups and C alkylsulfonylamino 1-6 1-6 groups are unsubstituted or substituted with one or more identical or different 15 substituents independently selected from the substituent set V ), C cycloalkoxy groups, C cycloalkylamino groups, C cycloalkylthio groups, C cycloalkylcarbonyl 3-6 3-6 3-6 groups and C cycloalkylsulfonyl groups (the C cycloalkoxy groups, the C 3-6 3-6 3-6 cycloalkylamino groups, the C cycloalkylthio groups, the C cycloalkylcarbonyl 3-6 3-6 groups and the C cycloalkylsulfonyl groups unsubstituted or substituted with one or 20 more identical or different substituents independently selected from the substituent set V )], a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof.

2. The compound according to Claim 1, which is represented by the formula (I ): 1b b (R ) b ( I ) 25 [wherein the ring A is represented by the formula (II ): (II ) 1b 4b 5b 17b 1b (wherein T is CR R , C(=O), C(=S), C(=NR ), a sulfur atom, S(=O) or S(=O) , U 6b 1b 8b b is a nitrogen atom or CR , and W is a nitrogen atom or CR ), the formula (III ): (III ) 2b 4b 2b 6b 2b 8b 9b 30 (wherein T is CR , U is a nitrogen atom or CR , and W is CR R , C(=O), C(=S), 17b 10b C(=NR ), NR , an oxygen atom, a sulfur atom, S(=O) or S(=O) (provided that when 2b 6b 2b b U is CR , W is not C(=O))), or the formula (IV ): 3b (IV ) 3b 4b 5b 17b 3b (wherein T is CR R , C(=O), C(=S), C(=NR ), a sulfur atom, S(=O) or S(=O) , U 6b 7b 17b 10b 5 is CR R , C(=O), C(=S), C(=NR ), NR , an oxygen atom, a sulfur atom, S(=O) or 3b 8b 9b 17b 11b S(=O) , and W is CR R , C(=O), C(=S), C(=NR ), NR , an oxygen atom, a sulfur 3b 4b 5b 3b 6b 7b 3b atom, S(=O) or S(=O) (provided that when T is CR R and U is CR R , W is 8b 9b not CR R )), b 15b X is a nitrogen atom or CR , b 16b 10 Y is CR , R is a hydrogen atom, a halogen atom, a C alkyl group or a C haloalkyl group, 1-6 1-6 the ring B is a C cycloalkane, a C cycloalkene, a 3 to 11-membered non-aromatic 3-11 3-11 heterocycle, a C aromatic carbocycle or a 5 to 10-membered aromatic heterocycle, 6-14 L is a single bond, a C alkylene group, a C alkenylene group or a C alkynylene 1-6 2-6 2-6 15 group (the C alkylene group, the C alkenylene group and the C alkynylene group 1-6 2-6 2-6 are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, amino groups, cyano groups and nitro groups), L is a single bond, a C alkylene group, a C alkenylene group or a C alkynylene 1-6 2-6 2-6 20 group (the C alkylene group, the C alkenylene group and the C alkynylene group 1-6 2-6 2-6 are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, amino groups, cyano groups and nitro groups), 3b b b L is a single bond or represented by any of the following formulae (V -1) to (V -20): O S S 12b 1b b b R E ( V -1 ) ( V -2 ) b b b b (V -3 ) (V -4 ) ( V -5 ) ( V -6 ) 1b 13b b b b b b ( V -7 ) (V -8 ) (V -9 ) (V -10 ) ( V -11 ) ( V ) 1b 1b O N N N 12b 12b 13b R R R b b b b b (V -12 ) (V -13 ) ( V -14 ) ( V -15 ) (V -16 ) 1b 1b 14b E E R O N N N N N 12b 12b 13b 12b 13b R R R R R b b b b (V -17 ) ( V -18 ) (V -19 ) (V -20 ) 1b 18b (wherein E is an oxygen atom, a sulfur atom or NR ), 3b 2b when L is a single bond, R is a hydrogen atom, a halogen atom, a C cycloalkyl 3-11 group, a 3 to 11-membered non-aromatic heterocyclyl group, a C aryl group or a 5 to 6-14 5 10-membered aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11- 3-11 membered non-aromatic heterocyclyl group, the C aryl group and the 5 to 10- 6-14 membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), 3b 2b 10 when L is not a single bond, R is a hydrogen atom, a C alkyl group, a C alkenyl 1-6 2-6 group (the C alkyl group and the C alkenyl group are unsubstituted or substituted 1-6 2-6 with one or more identical or different substituents independently selected from the substituent set V ), a C cycloalkyl group, a 3 to 11-membered non-aromatic 3-11 heterocyclyl group, a C aryl group or a 5 to 10-membered aromatic heterocyclyl 6-14 15 group (the C cycloalkyl group, the 3 to 11-membered non-aromatic heterocyclyl 3-11 group, the C aryl group and the 5 to 10-membered aromatic heterocyclyl group are 6-14 unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), n is 0, 1 or 2, 20 R is a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a sulfamoyl group, a phosphono group, a phosphonooxy group, a sulfo group, a sulfoxy group, a tetrazolyl group, a halogen atom, a cyano group, a nitro group, a C alkyl group, a C haloalkyl group, a C cycloalkyl group, a C alkenyl group, a C 1-6 3-11 2-6 2-6 haloalkenyl group, a C alkoxy group, a C haloalkoxy group, a C alkylthio group, a 1-6 1-6 1-6 C haloalkylthio group, a C alkylcarbonyl group, a C haloalkylcarbonyl group, a C 1-6 1-6 1-6 1- alkylsulfonyl group, a C haloalkylsulfonyl group, a C alkoxycarbonyl group, a 6 1-6 1-6 mono-C alkylamino group, a di-C alkylamino group, a mono-C 1-6 1-6 1-6 5 alkylaminocarbonyl group, a di-C alkylaminocarbonyl group or a C 1-6 1-6 b 3b alkylcarbonylamino group (when n is 2, R ’s may be identical or different), 4b 5b 6b 7b 8b 9b each of R , R , R , R , R and R is independently a hydrogen atom, a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a tetrazolyl group, a halogen atom, a cyano group, a C alkyl group, a C alkenyl group, a C alkoxy 1-6 2-6 1-6 10 group, a C alkylthio group, a C alkylcarbonyl group, a C alkylsulfonyl group, a 1-6 1-6 1-6 mono-C alkylamino group, a di-C alkylamino group (the C alkyl group, the C 1-6 1-6 1-6 2-6 alkenyl group, the C alkoxy group, the C alkylthio group, the C alkylcarbonyl 1-6 1-6 1-6 group, the C alkylsulfonyl group, the mono-C alkylamino group and the di-C 1-6 1-6 1-6 alkylamino group are unsubstituted or substituted with one or more identical or different 15 substituents independently selected from the substituent set V ), a C alkoxycarbonyl group, a C cycloalkyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a 3-11 C aryl group or a 5 to 10-membered aromatic heterocyclyl group (the C cycloalkyl 6-14 3-11 group, the 3 to 11-membered non-aromatic heterocyclyl group, the C aryl group and 6-14 the 5 to 10-membered aromatic heterocyclyl group are unsubstituted or substituted with 20 one or more identical or different substituents independently selected from the substituent set V ), 10b 11b each of R and R is independently a hydrogen atom, a C alkyl group, a C 1-6 2-6 alkenyl group, a C alkylcarbonyl group, a C alkylsulfonyl group, a C 1-6 1-6 1-6 alkoxycarbonyl group, a mono-C alkylaminocarbonyl group, a di-C 1-6 1-6 25 alkylaminocarbonyl group (the C alkyl group, the C alkenyl group, the C 1-6 2-6 1-6 alkylcarbonyl group, the C alkylsulfonyl group, the C alkoxycarbonyl group, the 1-6 1-6 mono-C alkylaminocarbonyl group and the di-C alkylaminocarbonyl group are 1-6 1-6 unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a C cycloalkyl group, a 3 to 11- 3-11 30 membered non-aromatic heterocyclyl group, a C aryl group or a 5 to 10-membered 6-14 aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11-membered non- 3-11 aromatic heterocyclyl group, the C aryl group and the 5 to 10-membered aromatic 6-14 heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), 12b 13b 14b 35 each of R , R and R is independently a hydrogen atom, a C alkyl group or a C 1-6 1- haloalkyl group (the C alkyl group and the C haloalkyl group are unsubstituted or 6 1-6 1-6 substituted with one or more identical or different substituents independently selected from the substituent set V ), 15b 16b each of R and R is independently a hydrogen atom, a halogen atom, a cyano 40 group, a carbamoyl group, a C alkyl group, a C haloalkyl group, a C cycloalkyl 1-6 1-6 3-11 group, a C alkoxy group, a C haloalkoxy group, a C alkylthio group, a C 1-6 1-6 1-6 1-6 alkylcarbonyl group, a C alkylsulfonyl group, a 3 to 11-membered non-aromatic heterocyclyl group, a C aryl group or a 5 to 10-membered aromatic heterocyclyl 6-14 group, 17b 18b 45 each of R and R is independently a hydrogen atom, a hydroxy group, a cyano group, a nitro group, a C alkyl group or a C alkoxy group, 1-6 1-6 the substituent set V consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C alkyl groups, C haloalkyl groups, C cycloalkyl groups, C alkenyl groups, C 1-6 1-6 3-11 2-6 2-6 haloalkenyl groups, C alkoxy groups, C haloalkoxy groups, C alkylthio groups, C 1-6 1-6 1-6 1- 5 haloalkylthio groups, C alkylcarbonyl groups, C haloalkylcarbonyl groups, C 6 1-6 1-6 1-6 alkylsulfonyl groups, C haloalkylsulfonyl groups, C alkoxycarbonyl groups, 3 to 11- 1-6 1-6 membered non-aromatic heterocyclyl groups, mono-C alkylamino groups, di-C 1-6 1-6 alkylamino groups, mono-C alkylaminocarbonyl groups, di-C alkylaminocarbonyl 1-6 1-6 groups and C alkylcarbonylamino groups, 2b 1b 10 the substituent set V consists of the groups in the substituent set V and C aryl 6-14 groups and 5 to 10-membered aromatic heterocyclyl groups (the C aryl groups and 5 6-14 to 10-membered aromatic heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), 15 the substituent set V consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C alkoxy groups, C haloalkoxy groups, C alkylthio groups, C haloalkylthio 1-6 1-6 1-6 1-6 groups, C alkylcarbonyl groups, C haloalkylcarbonyl groups, C alkylsulfonyl 1-6 1-6 1-6 20 groups, C haloalkylsulfonyl groups, C alkoxycarbonyl groups, mono-C alkylamino 1-6 1-6 1-6 groups, di-C alkylamino groups, mono-C alkylaminocarbonyl groups, di-C 1-6 1-6 1-6 alkylaminocarbonyl groups, C alkylcarbonylamino groups, C cycloalkyl groups, 3 to 1-6 3-11 11-membered non-aromatic heterocyclyl groups, C aryl groups and 5 to 10- 6-14 membered aromatic heterocyclyl groups (the C cycloalkyl groups, the 3 to 11- 3-11 25 membered non-aromatic heterocyclyl groups, the C aryl groups and the 5 to 10- 6-14 membered aromatic heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), the substituent set V consists of hydroxy groups, amino groups, carboxy groups, 30 carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C alkyl groups, C alkenyl groups, C alkoxy groups, C alkylthio groups, C 1-6 2-6 1-6 1-6 1-6 alkylcarbonyl groups, C alkylsulfonyl groups, C alkoxycarbonyl groups, mono-C 1-6 1-6 1-6 alkylamino groups, di-C alkylamino groups, mono-C alkylaminocarbonyl groups, di- 1-6 1-6 35 C alkylaminocarbonyl groups, C alkylcarbonylamino groups (the C alkyl groups, 1-6 1-6 1-6 the C alkenyl groups, the C alkoxy groups, the C alkylthio groups, the C 2-6 1-6 1-6 1-6 alkylcarbonyl groups, the C alkylsulfonyl groups, the C alkoxycarbonyl groups, the 1-6 1-6 mono-C alkylamino groups, the di-C alkylamino groups, the mono-C 1-6 1-6 1-6 alkylaminocarbonyl groups, the di-C alkylaminocarbonyl groups and the C 1-6 1-6 40 alkylcarbonylamino groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), C 3-11 cycloalkyl groups, 3 to 11-membered non-aromatic heterocyclyl groups, C aryl 6-14 groups and 5 to 10-membered aromatic heterocyclyl groups (the C cycloalkyl groups, 3-11 the 3 to 11-membered non-aromatic heterocyclyl groups, the C aryl groups and the 5 6-14 45 to 10-membered aromatic heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), and the substituent set V consists of hydroxy groups, amino groups, carboxy groups, carbamoyl groups, sulfamoyl groups, phosphono groups, phosphonooxy groups, sulfo groups, sulfoxy groups, tetrazolyl groups, halogen atoms, cyano groups, nitro groups, C alkoxy groups, C alkylthio groups, C alkylcarbonyl groups, C alkylsulfonyl 1-6 1-6 1-6 1-6 5 groups, C alkoxycarbonyl groups, mono-C alkylamino groups, di-C alkylamino 1-6 1-6 1-6 groups, mono-C alkylaminocarbonyl groups, di-C alkylaminocarbonyl groups, C 1-6 1-6 1-6 alkylcarbonylamino groups, C cycloalkyl groups, 3 to 11-membered non-aromatic 3-11 heterocyclyl groups, C aryl groups and 5 to 10-membered aromatic heterocyclyl 6-14 groups (the C alkoxy groups, the C alkylthio groups, the C alkylcarbonyl groups, 1-6 1-6 1-6 10 the C alkylsulfonyl groups, the C alkoxycarbonyl groups, the mono-C alkylamino 1-6 1-6 1-6 groups, the di-C alkylamino groups, the mono-C alkylaminocarbonyl groups, the di- 1-6 1-6 C alkylaminocarbonyl groups, the C alkylcarbonylamino groups, the C cycloalkyl 1-6 1-6 3-11 groups, the 3 to 11-membered non-aromatic heterocyclyl groups, the C aryl groups 6-14 and the 5 to 10-membered aromatic heterocyclyl groups are unsubstituted or 15 substituted with one or more identical or different substituents independently selected from the substituent set V )], a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof.

3. The compound according to Claim 2, wherein R is a hydrogen atom, a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. b 15b 20

4. The compound according to Claim 2 or 3, wherein X is a nitrogen atom or CR (wherein R is a hydrogen atom, a halogen atom, a cyano group, a C alkyl group, a C haloalkyl group or a C cycloalkyl group), and 1-3 3-6 b 16b 16b Y is CR (wherein R is a hydrogen atom), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. b 15b 25

5. The compound according to Claim 4, wherein X is a nitrogen atom or CR (wherein R is a hydrogen atom or a halogen atom), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof.

6. The compound according to any one of Claims 2 to 5, wherein the ring A is represented by the formula (II ): (II ) 1b 4b 5b 1b 6b (wherein T is CR R , C(=O), C(=S) or S(=O) , U is a nitrogen atom or CR , and 1b 8b b W is CR ), the formula (III ): (III ) 2b 4b 2b 2b (wherein T is CR , U is a nitrogen atom, and W is C(=O) or C(=S)) or the formula 35 (IV ): 3b (IV ) 3b 4b 5b 3b 10b 3b 8b 9b (wherein T is CR R , U is NR or an oxygen atom, and W is CR R , C(=O) or C(=S)), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. 5

7. The compound according to any one of Claims 2 to 5, wherein the ring A is represented by any of the following formulae (XVIII -1) to (XVIII -8): 8b 8b R R R N N N N N N b b b b (XVIII -1 ) (XVIII -2 ) (XVIII -3 ) (XVIII -4 ) ( XVIII ) 2b 9b E 8b 5b E b b b b (XVIII -5 ) (XVIII -6 ) (XVIII -7 ) ( XVIII -8 ) 2b 3b (wherein each of E and E is independently an oxygen atom or a sulfur atom, each of 4b 5b 6b 8b 9b R , R , R , R and R is independently a hydrogen atom, a halogen atom or a C 10 alkyl group, and R is a hydrogen atom or a C alkyl group), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof.

8. The compound according to any one of Claims 2 to 7, wherein L is a single bond, L is a single bond, a C alkylene group or a C alkenylene group (the C alkylene 1-6 2-6 1-6 group and the C alkenylene group are unsubstituted or substituted with one or more 15 identical or different substituents independently selected from the group consisting of a halogen atoms, hydroxy groups, amino groups, cyano groups and nitro groups), the ring B is a C cycloalkane, a C cycloalkene, a 3 to 11-membered non-aromatic 3-11 3-11 heterocycle, a C aromatic carbocycle or a 5 to 10-membered aromatic heterocycle, 6-14 n is, 0 or 1, 20 R is a hydroxy group, an amino group, a halogen atom, a cyano group, a C alkyl group, a C haloalkyl group, a C cycloalkyl group, a C alkoxy group, a C 1-3 3-6 1-3 1-3 haloalkoxy group or a C alkylsulfonyl group, L is a single bond, and R is a hydrogen atom, a halogen atom, a C cycloalkyl group, a 3 to 11-membered 3-11 25 non-aromatic heterocyclyl group, a phenyl group, a naphthyl group or a 5 to 10- membered aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11- 3-11 membered non-aromatic heterocyclyl group, the phenyl group, the naphthyl group and the 5 to 10-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof.

9. The compound according to any one of Claims 2 to 7, wherein L is a single bond 5 or a C alkylene group, L is a single bond or a C alkylene group (the C alkylene group is unsubstituted or 1-3 1-3 substituted with a cyano group or a C haloalkyl group), the ring B is a C cycloalkane, a C cycloalkene, a 3 to 11-membered non-aromatic 3-11 3-11 heterocycle, benzene or a 5 to 6-membered aromatic heterocycle, 10 n is, 0 or 1, R is a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a tetrazolyl group, a halogen atom, a cyano group, a nitro group, a C alkyl group, a C 1-3 1-3 haloalkyl group, a C cycloalkyl group, a C alkoxy group, a C haloalkoxy group or 3-6 1-3 1-3 a C alkylsulfonyl group, 15 L is a single bond, and R is a hydrogen atom, a halogen atom, a C cycloalkyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl 20 group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof.

10. The compound according to Claim 8, wherein the ring B is a C cycloalkane or 3-11 a 4 to 7-membered non-aromatic heterocycle, 25 n is 0 or 1, and R is a hydroxy group, a C alkyl group or a C alkoxy group, a tautomer or a 1-3 1-3 pharmaceutically acceptable salt of the compound or a solvate thereof.

11. The compound according to Claim 8 or 10, wherein L is a single bond, a C alkylene group, a C alkenylene group or a C haloalkylene group (the C alkylene 2-6 1-6 1-6 30 group, the C alkenylene group and the C haloalkylene group are unsubstituted or 2-6 1-6 substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups and cyano groups), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof.

12. The compound according to any one of Claims 8, 10 and 11, wherein R is a 35 hydrogen atom, a C cycloalkyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 10-membered aromatic heterocyclyl group (the 4 to 7- membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 10- membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting 40 of hydroxy groups, amino groups, carbamoyl groups, sulfamoyl groups, halogen atoms, cyano groups, nitro groups, C alkyl groups, C alkoxy groups, C alkylthio groups, 1-6 1-6 1-6 C alkylsulfonyl groups, mono-C alkylamino groups, di-C alkylamino groups, C 1-6 1-6 1-6 1-6 alkoxycarbonyl groups, mono-C alkylaminocarbonyl groups, di-C 1-6 1-6 alkylaminocarbonyl groups, C alkylcarbonylamino groups (the C alkyl groups, the 1-6 1-6 45 C alkoxy groups, the C alkylthio groups, the C alkylsulfonyl groups, the mono-C 1-6 1-6 1-6 1-6 alkylamino groups, the di-C alkylamino groups, the C alkoxycarbonyl groups, the 1-6 1-6 mono-C alkylaminocarbonyl groups, the di-C alkylaminocarbonyl groups and the C 1-6 1-6 1- alkylcarbonylamino groups are unsubstituted or substituted with one or more identical or different halogen atoms independently selected from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms or with a hydroxy group or a cyano group), C cycloalkyl groups, 4 to 7-membered non-aromatic heterocyclyl 5 groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof.

13. The compound according to Claim 12, wherein R is a hydrogen atom, a 4 to 7- membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 10-membered aromatic heterocyclyl group (the 4 to 7-membered non-aromatic heterocyclyl group, the 10 phenyl group and the 5 to 10-membered aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, halogen atoms, cyano groups, nitro groups, C alkyl groups (the C alkyl groups are unsubstituted or substituted with a cyano 1-3 1-3 group), C haloalkyl groups and C alkoxycarbonyl groups), a tautomer or a 1-3 1-6 15 pharmaceutically acceptable salt of the compound or a solvate thereof.

14. The compound according to any one of Claims 8 and 10 to 13, wherein L is a C alkylene group, a C alkenylene group (the C alkylene group and the C 6 2-3 1-6 2-3 alkenylene group are unsubstituted or substituted with a cyano group) or C haloalkylene group, and R is, a hydrogen atom, a tautomer or a pharmaceutically 20 acceptable salt of the compound or a solvate thereof.

15. The compound according to any one of Claims 2 to 7, wherein L is a single bond, L is a single bond, a C alkylene group or a C alkenylene group (the C alkylene 1-6 2-6 1-6 group and the C alkenylene group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of 25 halogen atoms, hydroxy groups, amino groups, cyano groups and nitro groups), the ring B is a C cycloalkane, a C cycloalkene, a 3 to 11-membered non-aromatic 3-11 3-11 heterocyclyl group, a C aryl group or a 5 to 10-membered aromatic heterocycle, 6-14 n is 0 or 1, R is a hydroxy group, an amino group, a halogen atom, a cyano group, a C alkyl 30 group, a C haloalkyl group, a C cycloalkyl group, a C alkoxy group or a C 1-3 3-6 1-3 1-3 haloalkoxy group, 3b b b L is represented by any of the following formulae (VI -1) to (VI -11): 12b 1b 12b E 1b O E 1b 1b 12b b b b b b b (VI -6 ) (VI -1 ) (VI -2 ) (VI -3 ) (VI -4 ) (VI -5 ) O O (VI ) 12b 13b 12b 13b R R 12b b b b (VI -10 ) (VI -11 ) (VI -7 ) (VI -8 ) (VI -9 ) 1b 12b 13b (wherein E is an oxygen atom or a sulfur atom, each of R and R is independently 35 a hydrogen atom, a C alkyl group or a C haloalkyl group (the C alkyl group and 1-6 1-6 1-6 the C haloalkyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, cyano groups, hydroxy group, C alkoxy groups, C alkylthio groups, C 1-6 1-6 1-6 alkylsulfonyl groups, C cycloalkyl groups, 4 to 7-membered non-aromatic heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups (the phenyl 5 groups and the 5 to 6-membered aromatic heterocyclyl groups are unsubstituted or substituted with a substituent selected from the group consisting of a halogen atom, a cyano group, a C alkyl group and a C haloalkyl group))), and 1-3 1-3 R is a hydrogen atom, a C alkyl group (the C alkyl group is unsubstituted or 1-6 1-6 substituted with one or more identical or different substituents independently selected 10 from the substituent set V ), a C cycloalkyl group, a 3 to 11-membered non-aromatic 3-11 heterocyclyl group, a phenyl group, a naphthyl group or a 5 to 10-membered aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11-membered non-aromatic 3-11 heterocyclyl group, the phenyl group, the naphthyl group and the 5 to 10-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical 15 or different substituents independently selected from the substituent set V ), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof.

16. The compound according to any one of Claims 2 to 7, wherein L is a single bond or a C alkylene group, L is a single bond or a C alkylene group (the C alkylene group is unsubstituted or 1-3 1-3 20 substituted with a cyano group or a C haloalkyl group), the ring B is a C cycloalkane, a C cycloalkene, a 3 to 11-membered non-aromatic 3-11 3-11 heterocycle, benzene or a 5 to 6-membered aromatic heterocycle, n is 0 or 1, R is a hydroxy group, an amino group, a carbamoyl group, a halogen atom, a cyano 25 group, a C alkyl group, a C haloalkyl group, a C cycloalkyl group, a C alkoxy 1-3 1-3 3-6 1-3 group, a C haloalkoxy group or a C alkylsulfonyl group, 1-3 1-3 3b b b L is represented by any of the following formulae (VI -1) to (VI -11): 12b E b b b b b (VI -6 ) (VI -1 ) (VI -2 ) (VI -3 ) (VI -4 ) (VI -5 ) O O (VI ) 12b 13b R 12b 13b b b b (VI -10 ) (VI -11 ) (VI -7 ) (VI -8 ) (VI -9 ) 1b 12b 13b (wherein E is an oxygen atom, each of R and R is independently a hydrogen 30 atom, a C alkyl group or a C haloalkyl group), and 1-6 1-6 R is a hydrogen atom, a C alkyl group (the C alkyl group is unsubstituted or 1-6 1-6 substituted with one or more identical or different substituents independently selected from the substituent set V ), a C cycloalkyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group 35 (the C cycloalkyl group, the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof.

17. The compound according to Claim 15, wherein the ring B is a C cycloalkane or 3-11 5 a 4 to 7-membered non-aromatic heterocycle, 3b b b L is represented by any of the following formulae (XIX -1) to (XIX -7): 1b 12b (wherein E is an oxygen atom, and R is a hydrogen atom, a C alkyl group (the C 1-6 1- alkyl group is unsubstituted or substituted with one or more identical or different 10 substituents independently selected from the group consisting of cyano groups, hydroxy groups, C alkoxy groups, C cycloalkyl groups and phenyl groups) or a C haloalkyl 1-3 3-6 1-6 group), and R is a hydrogen atom, a C alkyl group, a C haloalkyl group (the C alkyl group 1-6 1-6 1-6 and the C haloalkyl group are unsubstituted or substituted with one or two identical or 15 different substituents independently selected from the group consisting of hydroxy groups, cyano groups, C alkoxy groups, C alkylthio groups, C alkylsulfonyl groups, 1-3 1-3 1-3 C cycloalkyl groups, 4 to 7-membered non-aromatic heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups (the C cycloalkyl groups, the 4 to 7-membered non-aromatic heterocyclyl groups, the phenyl groups and the 5 to 20 6-membered aromatic heterocyclyl groups are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, cyano groups, C alkoxy groups, C haloalkoxy 1-6 1-6 groups and C alkoxycarbonyl groups)), a C cycloalkyl group, a 4 to 7-membered 1-6 3-6 non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic 25 heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, hydroxy groups, cyano groups, C alkyl groups, C haloalkyl groups, C alkoxy 1-6 1-6 1-6 30 groups, C haloalkoxy groups and C alkoxycarbonyl groups), a tautomer or a 1-6 1-6 pharmaceutically acceptable salt of the compound or a solvate thereof.

18. The compound according to Claim 15 or 17, wherein L is represented by any of the following formulae (XX -1) to (XX -4): 1b 12b (wherein E is an oxygen atom, and R is a hydrogen atom, a C alkyl group (the C 1-3 1- alkyl group is unsubstituted or substituted with a substituent selected from the group consisting of a cyano group, a hydroxy group, a C alkoxy group, a C cycloalkyl 1-3 3-6 5 group and a phenyl group) or C haloalkyl group)), and R is a hydrogen atom, a C alkyl group, a C haloalkyl group (the C alkyl group 1-3 1-3 1-3 and the C haloalkyl group are unsubstituted or substituted with one or two identical or different substituent selected from the group consisting of hydroxy groups, cyano groups, C alkoxy groups, C cycloalkyl groups, 4 to 7-membered non-aromatic heterocyclyl 1-3 3-6 10 groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups (the C cycloalkyl groups, the 4 to 7-membered non-aromatic heterocyclyl groups, the phenyl groups and the 5 to 6-membered aromatic heterocyclyl groups are unsubstituted or substituted with a hydroxy group or a halogen atom)), a C cycloalkyl group, a 4 to 7- membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered 15 aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non- aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, halogen atoms, cyano groups, C alkyl groups, C haloalkyl groups and C 1-6 1-3 1-6 20 alkoxycarbonyl groups), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof.

19. The compound according to any one of Claims 8 to 13 or 15 to 18, wherein L is a single bond or a C alkylene group, a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. 25

20. The compound according to any one of Claims 4 to 19, wherein X is a nitrogen 15b 15b atom or CR (wherein R is a hydrogen atom), and b 16b 16b Y is CR (wherein R is a hydrogen atom), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof.

21. The compound according to any one of Claims 6 to 20, wherein the ring A is 30 represented by any of the following formulae (VII -1) to (VII -7): 8b 8b 8b N N N N N O S R b b b b ( VII -1 ) ( VII -2 ) ( VII -3 ) ( VII -4 ) 2b 9b 8b b R (VII ) b b b ( VII -5 ) ( VII -6 ) ( VII -7 ) 2b 4b 5b 6b 8b 9b 10b (wherein E is an oxygen atom, and each of R , R , R , R , R and R is independently a hydrogen atom or a C alkyl group), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. 5

22. The compound according to any one of Claims 6 to 20, wherein the ring A is represented by any of the following formulae (XXXIII -1) to (XXXIII -3): 8b E 8b 6b R ( XXXIII ) b b b (XXXIII -1 ) (XXXIII -2) (XXXIII -3 ) 2b 4b 5b 8b 9b 10b (wherein E is an oxygen atom, and each of R , R , R , R and R are hydrogen atoms, and R is a hydrogen atom, a halogen atom or a C alkyl group), a tautomer or 10 a pharmaceutically acceptable salt of the compound or a solvate thereof.

23. The compound according to any one of Claims 9, 20 and 21, wherein L is a single bond, L is a C alkylene group, the ring B is a C cycloalkane or a 4 to 7-membered non-aromatic heterocycle, 15 n is 0 or 1, R is a C alkyl group, L is a single bond, and R is a hydrogen atom or a phenyl group (the phenyl group is unsubstituted or substituted with one or more identical or different halogen atoms independently selected 20 from the group consisting of fluorine atoms, chlorine atoms, bromine atoms and iodine atoms), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof.

24. The compound according to any one of Claims 9, 20 and 21, wherein L is a single bond,

25 L is a single bond, the ring B is a C cycloalkane or a 4 to 7-membered non-aromatic heterocycle, n is 0, L is a single bond, and R is a hydrogen atom, a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. 5 25. The compound according to any one of Claims 16, 20 and 21, wherein L is a single bond, L is a single bond, the ring B is a C cycloalkane or a 4 to 7-membered non-aromatic heterocycle, n is 0 or 1, 10 R is a C alkyl group, 3b b b L is represented by any of the following formula (VIII -1) or (VIII -2): ( VIII ) (VIII -1) (VIII -2) , and R is a C alkyl group (the C alkyl group is unsubstituted or substituted with a cyano 1-6 1-6 group or a C cycloalkyl group) or a C haloalkyl group, a tautomer or a 3-6 1-3 15 pharmaceutically acceptable salt of the compound or a solvate thereof.

26. The compound according to any one of Claims 2 to 25, wherein the ring B is cyclohexane or piperidine, a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof.

27. The compound according to any one of Claims 2 to 22, wherein the ring B is a 4 20 to 7-membered non-aromatic heterocycle, a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof. b 15b

28. The compound according to Claim 1, wherein X is a nitrogen atom or CR (wherein R is a hydrogen atom or a halogen atom), b 16b 16b Y is CR (wherein R is a hydrogen atom), 25 R is a hydrogen atom, b b b the ring A is represented by any of the following formulae (XVIII -1) to (XVIII -8): 8b 8b N N N N N N b b b b (XVIII -1 ) (XVIII -2 ) (XVIII -3 ) (XVIII -4 ) ( XVIII ) 2b 9b E 8b 5b E b b b b (XVIII -5 ) (XVIII -6 ) (XVIII -7 ) ( XVIII -8 ) 2b 3b (wherein each of E and E is independently an oxygen atom or a sulfur atom, each of 4b 5b 6b 8b 9b R , R , R , R and R is independently a hydrogen atom, a halogen atom or a C alkyl group, and R is a hydrogen atom, a C alkyl group (the C alkyl group is 1-6 1-6 unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V ), a C cycloalkyl group, a 3 to 11- 3-11 membered non-aromatic heterocyclyl group, a C aryl group or a 5 to 10-membered 6-14 5 aromatic heterocyclyl group (the C cycloalkyl group, the 3 to 11-membered non- 3-11 aromatic heterocyclyl group, the C aryl group and the 5 to 10-membered aromatic 6-14 heterocyclyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V )), the ring B is a C cycloalkane, a 3 to 11-membered non-aromatic heterocycle, a C 3-11 6-14 10 aromatic carbocycle or a 5 to 10-membered aromatic heterocycle, L is single bond or a C alkylene group, L is a single bond, a C alkylene group or a C alkenylene group (the C alkylene 1-6 2-6 1-6 group and the C alkenylene group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of 15 halogen atoms, hydroxy groups, amino groups, cyano groups and nitro groups), n is 0 or 1, R is a hydroxy group, an amino group, a carboxy group, a carbamoyl group, a tetrazolyl group, a halogen atom, a cyano group, a nitro group, a C alkyl group, a C 1-3 1-3 haloalkyl group, a C cycloalkyl group, a C alkoxy group, a C haloalkoxy group or 3-6 1-3 1-3 20 a C alkylsulfonyl group, 3b b b L is a single bond or represented by any of the following formulae (XXII -1) to (XXII - 15): 1b 12b 13b (wherein E is an oxygen atom or a sulfur atom, and each of R and R is 25 independently a hydrogen atom, a C alkyl group or a C haloalkyl group (the C 1-6 1-6 1-6 alkyl group and the C haloalkyl group are unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, cyano groups, hydroxy groups, C alkoxy groups, C alkylthio 1-6 1-6 groups, C alkylsulfonyl groups, C cycloalkyl groups, 4 to 7-membered non-aromatic 1-6 3-6 30 heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups (the phenyl groups and 5 to 6-membered aromatic heterocyclyl groups are unsubstituted or substituted with a substituent selected from the group consisting of a halogen atom, a cyano group, a C alkyl group and a C haloalkyl group))), 1-3 1-3 3b 2b when L is a single bond, R is a hydrogen atom, a halogen atom, a C cycloalkyl 3-11 5 group, a 3 to 11-membered non-aromatic heterocyclyl group, a phenyl group, a naphthyl group, a 5 to 10-membered aromatic heterocyclyl group, a 8 to 11-membered partially saturated aromatic cyclic group or a 8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon group (the C cycloalkyl group, the 3 to 11-membered non- 3-11 aromatic heterocyclyl group, the phenyl group, the naphthyl group, the 5 to 10- 10 membered aromatic heterocyclyl group, the 8 to 11-membered partially saturated aromatic cyclic group and the 8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set V and the substituent set V ), 3b 2b 15 when L is not a single bond, R is a hydrogen atom, a C alkyl group, a C alkenyl 1-6 2-6 group (the C alkyl group and the C alkenyl group are unsubstituted or substituted 1-6 2-6 with one or more identical or different substituents independently selected from the 6b 9b substituent set V and the substituent set V ), a C cycloalkyl group, a 3 to 11- 3-11 membered non-aromatic heterocyclyl group, a C aryl group, a 5 to 10-membered 6-14 20 aromatic heterocyclyl group, a 8 to 11-membered partially saturated aromatic cyclic group or a 8 to 11-membered aromatic ring-condensed alicyclic hydrocarbon group (the C cycloalkyl group, the 3 to 11-membered non-aromatic heterocyclyl group, the C 3-11 6-14 aryl group, the 5 to 10-membered aromatic heterocyclyl group, the 8 to 11-membered partially saturated aromatic cyclic group or the 8 to 11-membered aromatic ring- 25 condensed alicyclic hydrocarbon group are unsubstituted or substituted with one or more identical or different substituents independently selected from the substituent set 4b 9b V and the substituent set V ), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof.

29. The compound according to Claim 1 or 28, wherein the ring A is represented by 30 any of the following formulae (XXI -1) to (XXI -4): 9b 2b 8b E R 10b 10b 6b R O N b N N N N ( XXI ) 5b E b b b b (XXI -1 ) (XXI -2) (XXI -3 ) ( XXI -4 ) 2b 3b 4b 5b (wherein each of E and E is independently an oxygen atom or a sulfur atom, R , R , 8b 9b 6b R and R are hydrogen atoms, R is a hydrogen atom, a halogen atom or a C alkyl group, and R is a hydrogen atom, a C alkyl group (the C alkyl group is 1-6 1-6 35 unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of cyano groups, hydroxy groups, C alkoxy groups, C alkylthio groups, mono-C alkylamino groups, di-C alkylamino 1-3 1-3 1-3 groups, mono-C alkylaminocarbonyl groups, di-C alkylaminocarbonyl groups, C 1-3 1-3 3-6 cycloalkyl groups, 4 to 7-membered non-aromatic heterocyclyl groups, phenyl groups 40 and 5 to 6-membered aromatic heterocyclyl groups (the phenyl groups and the 5 to 6- membered aromatic heterocyclyl groups are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of halogen atoms, C alkyl groups and C haloalkyl groups)), a C haloalkyl group, a 1-3 1-3 1-6 C cycloalkyl group or a 4 to 7-membered non-aromatic heterocyclyl group), a 5 tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof.

30. The compound according to any one of Claims 1, 28 and 29, wherein the ring A is represented by the following formulae (XXIX -1) or (XXIX -2): ( XXIX ) ( XXIX -1) (XXIX -2) 2b 3b 6b (wherein E and E are oxygen atoms, R is a hydrogen atom, a halogen atom or a 8b 10b 10 C alkyl group, R is a hydrogen atom, and R is a hydrogen atom, a C alkyl group 1-3 1-6 (the C alkyl group is unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of cyano groups, hydroxy groups, C alkoxy groups, C alkylthio groups, di-C alkylamino groups, C 1-3 1-3 1-3 3-6 cycloalkyl groups and 4 to 7-membered non-aromatic heterocyclyl groups), a C 15 haloalkyl group, a C cycloalkyl group or a 4 to 7-membered non-aromatic heterocyclyl group, a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof.

31. The compound according to any one of Claims 1 and 18 to 30, wherein L is a single bond, 20 L is a single bond, a C alkylene group, a C alkenylene group or a C 1-6 2-6 1-6 haloalkylene group (the C alkylene group, the C alkenylene group and the C 1-6 2-6 1-6 haloalkylene group are unsubstituted or substituted with a hydroxy group or a cyano group), the ring B is a C cycloalkane or a 4 to 7-membered non-aromatic heterocycle, 3-11 25 n is 0 or 1, and R is a hydroxy group, a C alkyl group or a C alkoxy group, a tautomer or a 1-3 1-3 pharmaceutically acceptable salt of the compound or a solvate thereof.

32. The compound according to any one of Claims 1 and 28 to 31, wherein L is a single bond, and 30 R is a hydrogen atom, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group, a 5 to 10-membered aromatic heterocyclyl group or a 8 to 11-membered partially saturated aromatic cyclic group (the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group, the 5 to 10-membered aromatic heterocyclyl group and the 8 to 11- membered partially saturated aromatic cyclic group are unsubstituted or substituted with 35 one or more identical or different substituents independently selected from the group consisting of hydroxy groups, amino groups, carbamoyl groups, sulfamoyl groups, halogen atoms, cyano groups, nitro groups, C alkyl groups (the C alkyl groups are 1-6 1-6 unsubstituted or substituted with a cyano group), C haloalkyl groups, C cycloalkyl 1-6 3-11 groups, C alkoxy groups, C haloalkoxy groups, C alkylthio groups, C 1-6 1-6 1-6 1-6 40 haloalkylthio groups, C alkylsulfonyl groups, C haloalkylsulfonyl groups, C 1-6 1-6 1-6 alkoxycarbonyl groups, 4 to 7-membered non-aromatic heterocyclyl groups, mono-C alkylamino groups, di-C alkylamino groups, phenyl groups, 5 to 6-membered aromatic heterocyclyl groups, mono-C alkylaminosulfonyl groups and di-C alkylaminosulfonyl 1-6 1-6 groups), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate 5 thereof.

33. The compound according to Claim 32, wherein R is a hydrogen atom, a phenyl group, a 5 to 10-membered aromatic heterocyclyl group or a 8 to 11-membered partially saturated aromatic cyclic group (the phenyl group, the 5 to 10-membered aromatic heterocyclyl group and the 8 to 11-membered partially saturated aromatic cyclic group 10 are unsubstituted or substituted with one, two or three identical or different substituents independently selected from the group consisting of halogen atoms, cyano groups, nitro groups, C alkyl groups, C haloalkyl groups and C alkoxycarbonyl groups), a 1-3 1-3 1-6 tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof.

34. The compound according to Claim 32, wherein R is a 4 to 7-membered non- 15 aromatic heterocyclyl group (the 4 to 7-membered non-aromatic heterocyclyl group is unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, halogen atoms, cyano groups, C alkyl groups (the C alkyl groups are unsubstituted or substituted 1-3 1-3 with a cyano group) and C haloalkyl groups), a tautomer or a pharmaceutically 20 acceptable salt of the compound or a solvate thereof.

35. The compound according to any one of Claims 1 and 28 to 31, wherein L is represented by any of the following formulae (XIX -1) to (XIX -7): 1b 12b (wherein E is an oxygen atom, and R is a hydrogen atom or a C alkyl group (the 25 C alkyl group is unsubstituted or substituted with one or more identical or different substituents independently selected from the group consisting of halogen atoms, cyano groups, hydroxy groups, C allkoxy groups, C cycloalkyl groups, 4 to 7-membered 1-3 3-6 non-aromatic heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups)), and 30 R is a hydrogen atom, a C alkyl group, a C haloalkyl group (the C alkyl group 1-6 1-6 1-6 and the C haloalkyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of cyano groups, hydroxy groups, C alkoxy groups, C alkylthio groups, C alkylsulfonyl groups, C 1-6 1-6 1-6 3-6 cycloalkyl groups, 4 to 7-membered non-aromatic heterocyclyl groups, phenyl groups 35 and 5 to 6-membered aromatic heterocyclyl groups (the C cycloalkyl groups, the 4 to 7-membered non-aromatic heterocyclyl groups, the phenyl groups and the 5 to 6- membered aromatic heterocyclyl groups are unsubstituted or substituted with one, two or three identical or different substituents independently selected from the group consisting of the substituent set V , mono-C alkylaminosulfonyl groups and di-C 1-6 1-6 alkylaminosulfonyl groups)), a C cycloalkyl group, a 4 to 7-membered non-aromatic heterocyclyl group, a phenyl group, a 5 to 6-membered aromatic heterocyclyl group or a 5 8 to 11-membered partially saturated aromatic cyclic group (the C cycloalkyl group, the 4 to 7-membered non-aromatic heterocyclyl group, the phenyl group, the 5 to 6- membered aromatic heterocyclyl group and the 8 to 11-membered partially saturated aromatic cyclic group are unsubstituted or substituted with one, two or three identical or different substituents independently selected from the group consisting of the 10 substituent set V , mono-C alkylaminosulfonyl groups and di-C alkylaminosulfonyl 1-6 1-6 groups), a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof.

36. The compound according to Claim 35, wherein L is represented by any of the following formulae (XXXI -1) to (XXXI -5): ( XXXI ) b b b ( XXXI -5 ) ( XXXI -1 ) ( XXXI -2 ) ( XXXI -3 ) ( XXXI -4 ) 1b 12b (wherein E is an oxygen atom, and R is a hydrogen atom, a C alkyl group (the C 1-3 1- alkyl group is unsubstituted or substituted with a substituent selected from the group consisting of a cyano group, a hydroxy group, a C allkoxy group, a C cycloalkyl 1-3 3-6 group and a phenyl group) or C haloalkyl group), and 20 R is a hydrogen atom, a C alkyl group, a C haloalkyl group (the C alkyl group 1-6 1-6 1-6 and the C haloalkyl group are unsubstituted or substituted with one or two identical or different substituent selected from the group consisting of hydroxy groups, cyano groups, C alkoxy groups, C cycloalkyl groups, 4 to 7-membered non-aromatic heterocyclyl 1-3 3-6 groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups (the C 25 cycloalkyl groups, the 4 to 7-membered non-aromatic heterocyclyl groups, the phenyl groups and the 5 to 6-membered aromatic heterocyclyl groups are unsubstituted or substituted with a hydroxy group or a halogen atom)), a C cycloalkyl group, a 4 to 7- membered non-aromatic heterocyclyl group, a phenyl group or a 5 to 6-membered aromatic heterocyclyl group (the C cycloalkyl group, the 4 to 7-membered non- 30 aromatic heterocyclyl group, the phenyl group and the 5 to 6-membered aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of hydroxy groups, halogen atoms, cyano groups, C alkyl groups, C haloalkyl groups and C 1-3 1-3 1-6 alkoxycarbonyl groups), a tautomer or a pharmaceutically acceptable salt of the 35 compound or a solvate thereof.

37. The compound according to Claim 35, wherein L is represented by the formula (XXXII ): (wherein R is a hydrogen atom, a C alkyl group (the C alkyl group is 1-3 1-3 unsubstituted or substituted with a substituent selected from the group consisting of a cyano group, a hydroxy group, a C allkoxy group, a C cycloalkyl group and a phenyl 1-3 3-6 group) or a C haloalkyl group), and R is a hydrogen atom, a C alkyl group, a C haloalkyl group (the C alkyl group 1-3 1-3 1-3 5 and the C haloalkyl group are unsubstituted or substituted with one or two identical or different substituent selected from the group consisting of hydroxy groups, cyano groups, C alkoxy groups, C cycloalkyl groups (the C cycloalkyl groups are unsubstituted 1-3 3-6 3-6 or substituted with a hydroxy groups), 4 to 7-membered non-aromatic heterocyclyl groups, phenyl groups and 5 to 6-membered aromatic heterocyclyl groups), a C 10 cycloalkyl group or a 4 to 7-membered non-aromatic heterocyclyl group (the C cycloalkyl group and the 4 to 7-membered non-aromatic heterocyclyl group are unsubstituted or substituted with one or two identical or different substituents independently selected from the group consisting of C alkyl groups, C haloalkyl 1-3 1-3 groups and C alkoxycarbonyl groups), a tautomer or a pharmaceutically acceptable 15 salt of the compound or a solvate thereof.

38. The compound according to any one of Claims 1 or 28 to 37, wherein L is a single bond or a C alkylene group, and the ring B is cyclohexane or piperidine, a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof.

39. The compound according to any one of Claims 1 to 38, wherein n is 0 or 1, and 20 R is a C alkyl group, a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof.

40. The compound according to any one of Claims 1, 28 to 31 and 35, wherein R is 1b b 2b a hydrogen atom, L is a single bond, the ring B is a C cycloalkane, L is a C 3-11 1-6 3b b alkylene group, L is -O-, and n is 0, a tautomer or a pharmaceutically acceptable salt 25 of the compound or a solvate thereof.

41. A JAK inhibitor containing the compound as defined in any one of Claims 1 to 40, a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof, as an active ingredient.

42. A preventive, therapeutic or improving agent for diseases against which inhibition 30 of JAK is effective, which contains the JAK inhibitor as defined in Claim 41.

43. A therapeutic agent for articular rheumatism, which contains the JAK inhibitor as defined in Claim 41.

44. Medicament containing the compound as defined in any one of Claims 1 to 40, a tautomer or a pharmaceutically acceptable salt of the compound or a solvate thereof, as 35 an active ingredient.

45. A use of a compound as defined in any one of claims 1 to 40 in the manufacture of a medicament for preventing or treating a disease against which inhibition of JAK is effective.