WO1996023789A1 - Hexahydropyrazinoquinoline derivatives - Google Patents

Abstract

Hexahydropyrazinoquinoline derivatives having general formula (I), exhibiting excellent 5-HT1A receptor agonist effects and thus being useful as a preventive or remedy for anxiety, depression or symptoms in association with senile dementia, wherein R1 represents -CO-R3; R2 represents hydrogen; R3 represents alkyl, cycloalkyl, optionally substituted aryl, optionally substituted aralkyl, cycloalkylamino, optionally substituted arylamino or an optionally substituted heterocycle; or R?1 and R2¿ form together with the nitrogen atom, to which they are bonded, optionally substituted 2,4-dioxothiazolidin-3-yl or phthalimidyl; X represents -CH¿2?- or -O-; and m represents an integer of 2 to 6.

Description

 Meisei Livestock Hexahi Drovirazinoquinoline Derivative [Technical Field]

The present invention relates to hexahydrovirazinoquinoline derivatives and hexahydrobirazinoquino derivatives having excellent serotonin _1A receptor (hereinafter abbreviated as 5- _HT1A receptor) action, sedative action against mental stress and hallucination-suppressing action. The present invention _relates to a 5- _H1LA receptor agonist containing a phosphorus derivative as an active ingredient.

[Background technology]

The journal 'Ob Medicinal' Chemistry, Vol. 30, p. 1 (1987) [J. Med. Chem., 30, 1 (1987)] states that serotonin (hereinafter 5-HT) Is abbreviated directly or indirectly to physiological phenomena including appetite, memory, thermoregulation, sleep, sexual behavior, anxiety, g-disease, and hallucinations. By the way, many compounds having a serotonergic effect have been known so far, and those having a hexahydrobirazino quinoline skeleton are described in Journal of the Journal of “Obchi” Pharmaceuticals, Vol. , P. 83 (1991) [Eur. J. Pharmacol., 194, 83 (1931).] And the journal 'Ob' Medicinal 'Chemistry, Vol. 35, p. 2 years) [丄 Med. Chem., 35, 2369 (1992).], Cent Vilaquin (3-[(ρ-fluobenzoyl) provir] 1 2.3,4,4a, 5,6 — Hexahi Draw 11 (H) — Birazino [1,2—a] quinoline hydrochloride).

Centpyraquin

[Disclosure of the Invention]

The present inventors have conducted intensive studies over many years on the synthesis of hexahydrobirazinoquinoline derivatives and their pharmacological actions with the aim of developing excellent compounds that act on serotonergic nerves. Hexahydrobirazinoquinoline derivative has potent 5-HT _A receptor agonizing action, sedative action against mental stress, and phantasmagoric effect, has few side effects such as drowsiness, anxiety, B disease, high blood pressure, schizophrenia The present invention has been found to have a therapeutic or preventive action (particularly a therapeutic action) for sleep disorders, migraine, sexual dysfunction, sickness, dizziness, symptoms related to senile dementia (particularly delirium) and the like. completed.

The present invention provides a hexahydrovirazinoquinoline derivative having an excellent 5-HT _1A receptor agonistic action, a sedative action against mental stress, and a hallucinogenic action, a method for producing the same, and a 5-HT _1A receptor comprising the same as an active ingredient. Provide body agonists.

 The hexanehydrobirazinoquinoline derivative of the present invention has the general formula (I):

Or having the general formula (II).

In the above formula,

R ¹ represents a group having the formula: CO—R ³ ,

R ² represents a hydrogen atom,

Or R ′ and R ² represent a group having the general formula (III) or (IV) formed together with the nitrogen atom to which they are bonded,

(III) ^(IV)

R ³ is a d-C alkyl group, a C ₃ -C ₁₀ cycloalkyl group, and may have 1 to 3 substituents selected from the same or different from the following substituent group A. C ₆ -C ₁₄ aryl group, 1 to 3 of which may have a substituent C ₇ is selected same or different from the following substituent group a - C * _e Ararukiru group, mono C ₃ - C! . A cycloalkylamino group, a mono-C ₆ -C arylamino group which may have 1 to 3 substituents which are the same or different and are selected from the following S-substituent group A, or selected from the following substituent group A A 5- or 6-membered aromatic bi-violet ring group which may have one substituent or may be fused to a benzene ring (the bi-violet ring is a nitrogen atom, an acid purple atom, Containing one or two heteroatoms selected from the group consisting of the same or different atoms).

R ⁴ and R ⁵ are the same or different and each represent a hydrogen atom or a C, -C alkyl group; And

R ⁶ represents a C ₆ —C aryl group which may have 1 to 3 substituents, which are the same or different and are selected from the following substituent groups:

The B-substituent group A includes a halogen atom, a C, -C6 alkyl group, a halogeno (: 〖-C6 alkyl group, a -Cβ alkoxy group, a C, -C * alkoxy C, a -C * alkyl group, d -C * alkylthio group, 1 to 3 {C _s -C aryl group optionally having a B substituent (the B substituent is halogen, C, -C. Alkyl or -C alkoxy), a hydroxyl group, a thiol group, an amino group, a protected amino groups, carboxy sheet group, carboxy C l - C alkyl group, formyl group, C ₂ - C 5 Arukanoiru groups, C ₂ - C 5 alkoxycarbonyl group, a force Rubamoiru group, Represents a cyano group or a nitro group,

 X represents a methylene or acid purple atom,

 m represents a fraction of 2 to 6.

Further, the active ingredient of 5-HT _{l A} receptor agonist of the present invention is a Kisahi Dorobirajinokino phosphorus derivatives to having the above general formula (I) or one general formula (II).

 In the above general formula (I) or (II), the “halogen atom” in the definition of the substituent group A may be, for example, a fluorine atom, a salt atom, a bromine atom or an iodine atom, preferably a fluorine atom. It is a purple atom or a chlorine atom, more preferably a fluorine atom.

In the above, “(:, -C ₇ alkyl group)” in the definition of R ³ is, for example, a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, an s-butyl group, a t-alkyl group. Butyl, pentyl, isopentyl, 2-methylbutyl, neopentyl, 1-ethylpropyl, hexyl, 4-methylpentyl, 3-methylbentyl, 2-methylbentyl, 1-methylpentyl, 3, 3-dimethylbutyl group, 2.2-dimethylbutyl group, 1.1-dimethylbutyl group, 1,2-dimethylbutyl group, 1,3-dimethylbutyl group, 2,3-dimethylbutyl group, 2-ethylbutyl group, heptyl Group, 1-methylhexyl group, 2-methylhexyl group, 3-methylhexyl group, 4-methylhexyl group, 5-methylhexyl group, 1-ethylhexyl group, 2 Echirupenchiru group, a 3-Echirubenchiru group, 1 one It may be a linear or branched alkyl group having 1 to 7 carbon violet, such as a propyl butyl group or a 4,4-dimethylpentyl group, and is preferably a C, -alkyl group or a 1-methylhexyl group. A 1-ethylpentyl group or a 1-propyl butyl group, more preferably a butyl group, an isobutyl group, a s-butyl group, a t-butyl group or a 1-ethylpentyl group, and particularly preferably a t-butyl group or a 1-butylpentyl group. —Ethylpentyl group. In the above, R ⁵ and one C ₆ alkyl group in the definition of the substituent group A are `` the rc, one C ₇ alkyl group '' of the straight or branched C 1 to C ₆ alkyl group. The alkyl group of R ⁴ or R ⁵ is preferably a C, -C alkyl group, more preferably a methyl group, an ethyl group or an isopropyl group, and particularly preferably a methyl group. Group. The alkyl group in the S-substituent group A is preferably a C 1, 1C alkyl group, more preferably a methyl group or an ethyl group, and particularly preferably a methyl group.

In the above, the “halogen group, —C 6 alkyl group” in the definition of the substituent group A is the same as or different from the “halogen atom” and is one to three halogen atoms selected from the group consisting of rct-C _β An alkyl group ", for example, a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a 2-fluoroethyl group, a 2,2-difluoroethyl group, a 2,2,2-trifluoroethyl group, or a 3-fluorobutyl group. Bil group, 3,3,3-Trifluorobutyl mouth group, 4-Fluorobutyl group, Dichloromethyl group, Trichloromethyl group, 2-Chloroethyl group, 2,2,2-Trichloroethyl group, Dibromomethyl group, 2 —Bromoethyl, 2,2-dibromoethyl, 2-bromobutyl, 2-tert-butyl, 5-fluoropentyl, or 4-cyclohexyl And preferably a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a 2-fluoroethyl group, a 2,2-difluoroethyl group or a 2,2,2-trifluoromethyl group, and more preferably a trifluoromethyl group. Group.

In the above definition, “mono C ₃ —C, .cycloalkyl group” in the definition of R ³ is, for example, a cyclobutyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cyclohexyl group, a norbornyl group Or a fused ring such as an adamantyl group It may be a 3-10 shell saturated 璨 -hydrocarbon group, preferably a cyclopentyl group or a cyclohexyl group, and more preferably a cyclohexyl group.

The At a "C, - C _s alkoxy group" in the definition of substituent group A, the "C, - C _beta alkyl group" indicates a bonded groups to an oxygen atom, for example, main butoxy group, ethoxy Group, propoxy group, isopropoxy group, butoxy group, isobutoxy group, s-butoxy group, t-butoxy group, pentoxy group, isopentoxy group, 2-methylbutoxy group, neopentoxy group, 1-ethylbroboxyl group, Xyloxy, 4-methylpentoxy, 3-methylpentoxy, 2-methylpentoxy, 1-methylpentoxy, 3,3-dimethylbutoxy, 2,2-dimethylbutoxy, 1,1 -Dimethylbutoxy group, 1,2-dimethylbutoxy group, 1,3-dimethylbutoxy group, 2,3-dimethylbutoxy group or 2-ethylbutoxy group, and preferably d-C An alkoxy group, more preferably to the main butoxy group or an ethoxy group, particularly preferably a main butoxy group.

 In the above, the `` rc, -C alkoxy-alkyl group '' in the definition of the at substitution group A means a group in which the `` C, -C alkoxy group '' is bonded to the rc 〖-alkyl group, For example, a methoxymethyl group, a 1-methoxyl group, a 2-methoxyl group, a 1-methoxyl group, a 2-methoxyl group, a 3-methloxyl group, a 2-methloxylsopropyl group, a 4-methloxybutyl group, Methoxybutyl, 2-methoxybutyl, ethoxymethyl, ethoxymethyl, ethoxybutyl, propoxymethyl, butoxymethyl, butoxybutyl or t-butoxybutyl, preferably methoxymethyl Or an ethoxymethyl group, and more preferably a methoxymethyl group.

 In the above, the “rd-alkylthio group” in the definition of the substituent group A is, for example, a methylthio group, an ethylthio group, a propylthio group, an isobromothio group, a butylthio group, an isobutylthio group, an s-butylthio group or a t-alkylthio group. It may be a linear or branched alkylthio group having 1 to 4 carbon atoms such as a butylthio group, preferably a methylthio group or an ethylthio group, and more preferably a methylthio group.

In the above, in the definition of the substituent group A, "may have 1 to 3 B substituents" C _β- reel group (where the S substituent is halogen, C, -C ₄ alkyl or d —

C * alkoxy) is a carbon violet aromatic group having 6 to 14 carbon atoms which may have 1 to 3 substituents and is the same or different and selected from the group II. For example, a phenyl group, a fluorophenyl group, a chlorophenyl group, a dichlorophenyl group, a rhodofurnyl group, a methylphenyl group, a trimethylphenyl group, a butylphenyl group, a methoxyphenyl group, an ethoxyphenyl group, an indenyl group, a methylethyl group Benzyl, bromoindenyl, naphthyl, dichloronaphthyl, butoxynaphthyl, phenanthrenyl, butylphenanthrenyl, anthracenyl or dimethylanthracenyl, preferably fluorinated, chlorine, methyl And one or two S substituents selected from the group consisting of An I off group, more preferably a phenyl group, 4 one fluoro Der group, 4 one-methylphenyl group or a 4-menu Bok Kishifueniru group, particularly preferably a phenylene Le group.

In the above, the protecting group of the amino group of the “protected amino group” in the definition of the substituent group A can be generally used without particular limitation as long as it is a group used as a protecting group of the amino group. possible, for example, formyl group; Asechiru group, a propionyl group, a butyryl group, an isobutyryl group, Pentanoiru group, pivaloyl group, Bruno, 'Reriru groups, C such as I Sobareriru group or to Kisanoiru group ₂ - C Arukanoiru group; Kuroroa Cetyl group, dichloroacetyl group, trichloroacetyl group, trifluoroacetyl group, 3-fluorobutyral pionyl group, 4,4-dichlorobutyryl group, methoxyacetyl group, butoxyacetyl group, ethoxypropionyl group or brobo such as Kishibuchiriru group, halogen or d - C ₂ substituted alkoxy - C § Rukanoiru group An unsaturated C ₂ -C alkanoyl group such as an acryloyl group, a propioyl group, a methacryloyl group, a crotonyl group or an isocrotonyl group; a benzoyl group, an α-naphthyl group, a 3-naphthyl group, a 2-fluoro group Lobenzoyl group, 2-bromobenzoyl group, 2,4-dichlorobenzoyl group, 6-chloro-α-naphthyl group, 4-toluoyl group, 4-bromoylbenzoyl group, 4-t-butylbenzoyl group, 2, 4, 6-trimethylbenzoyl group, 6-ethyl-α-naph Toyl group, 4-anisyl group, 4-propoxybenzoyl group, 4-t-butoxybenzoyl group, 6-ethoxy-ot-naphthyl group, 2-ethoxycarbonylbenzoyl group, 4-t-butoxycarbonylbenzoyl group , 6-methoxycarbonyl mono-α-naphthyl group, 4-phenylbenzoyl group, 4-phenyl-naphthyl group, 6-α-naphthylbenzoyl group, 4-nitrobenzoyl block, 2 two Torobe Nzoiru such as group or 6 two Torrox α- naphthoyl group, a halogen, - C * alkyl, C 'one C «alkoxy, C ₂ - C s alkoxycarbonyl, C ₆ - C § rie A C, 1 C ₁₅ arylcarbonyl group which may be substituted with carbonyl or nitro; a methoxycarbonyl group, an ethoxycarbonyl group, a propoxycarbonyl group, an isobroboxoxycarbonyl group, a butyl group; Toxoxycarbonyl group, isobutoxycarbonyl group, s-butoxycarbonyl group, t-butoxycarbonyl group, chloromethoxycarbonyl group, 2,2,2—trichloromouth ethoxycarbonyl group, 2-fluorofluorocarbonyl group, 2— Bromo-t-butoxycarbonyl group, 2,2-dibromo-t-butoxycarbonyl group, triethylsilyl methoxycarbonyl group, 2-trimethylsilylethoxycarbonyl group, 4-tributyl bilsilyl butoxycarbonyl group or t-butyl A C ₂ -C 5 alkoxycarbonyl group which may be substituted with a halogen or tri-Calkylsilyl, such as a dimethylsilylpropoxycarbonyl group; a vinyloxycarbonyl group, an aryloxycarbonyl group, 1 , 3—Butagenyloxycarbonyl group or 2-benteni O C _3, such as alkoxycarbonyl group - C alkenyl O alkoxycarbonyl group: C _e such as phthaloyl group - C § reel dicarbonyl group; a benzyl group, phenethyl group, 3-Fueniruburobi group, 4 Fuwenirubuchiru group, alpha- naphthylmethyl group, / 3 - naphthylmethyl group, Jifuenirumechiru group, Application Benefits phenylmethyl group, alpha-C ₇ such as naphthyl diphenyl methyl group or a 9 one anthrylmethyl group - C _e Ararukiru group; or Benjiruo alkoxycarbonyl group , (1-phenyl) benzyloxycarbonyl group, α-naphthylmethyloxycarbonyl group, 0-naphthylmethyloxycarbonyl group, 9-phenylmethyloxycarbonyl group, Ρ-methoxybenzyloxycarbonyl Or methoxy or nitro, such as ρ-2 nitrobenzyloxycarbonyl group S in Russia C _e -C ₅ which may be replaced. It is a § Lal Kill O alkoxycarbonyl group, preferably a formyl group; C ₂ - C ₅ Arukanoiru group; preparative Riffle O b acetyl group or main preparative Kishiasechiru group: Benzoiru group, alpha-naphthoyl group, / 3- Naphthyl group, anisyl group or benzoyl group; methoxycarbonyl group, ethoxycarbonyl group, t-butoxycarbonyl group, 2,2,2-trichloromouth ethoxycarbonyl group, triethylsilyl methoxycarbonyl group Or 2-trimethylsilylethoxycarbonyl group; vinyloxycarbonyl group or aryloxycarbonyl group; phthaloyl group; benzyl group; or benzyloxycarbonyl group or ditrobenzyloxycarbonyl group. More preferably, formyl group, acetyl group, benzoyl group, Nisyl group, 412-nitrobenzoyl group, methoxycarbonyl, ethoxycarbonyl, butoxycarbonyl, t-butoxycarbonyl, phthaloyl, benzyl, benzyloxycarbonyl or p-nitrobenzo A carbonyl group, and particularly preferably an acetyl group.

In the above, the “mono C ₃ -C ₁₀ cycloalkylamino group” in the definition of R ³ is a group in which the above rc ₃ —C ₁₀ cycloalkyl group is bonded to an amino group. It can be a bilamino group, a cyclobutylamino group, a cyclopentylamino group, a cyclohexylamino group, a cycloheptylamino group, a norbornylamino group or an adamantylamino group, preferably a cyclobentylamino group. Or a cyclohexylamino group, more preferably a cyclohexylamino group.

In the above, the “carboxy C _t -C * alkyl group J” in the definition of the 31-substituent group A is a group in which a carboxy group is bonded to the rc, -C alkyl group, for example, a carboxymethyl group, A carboxyl group, a 2-carboxyethyl group, a carboxybutyl group, a 2-carboxybutyl pill group, a 3-carboxybutyl group, a 2-carboxyisopropyl group, a 4-carboxybutyl group or a 2-carboxymethyl group It may be a t-butyl group, preferably a carboxymethyl group or a 2-carboxyethyl group, and more preferably a carboxymethyl group.

In the above, the “C ₂ -C ₅ alkanol group” in the definition of the S-substituent group A is, for example, a carbon such as an acetyl group, a propionyl group, a butyryl group or an isopyryl group. It may be a linear or branched alkanoyl group having a violet number of 2 to 5, and is preferably an acetyl group.

In the above, the rc ₂ -c ₅ alkoxycarbonyl group j in the definition of the as substitution group A is a group in which a carbonyl group is bonded to the aforementioned re, -C alkoxy group '', for example, a methoxycarbonyl group, It may be an ethoxycarbonyl group, a propoxycarbonyl group, an isobromoxycarbonyl group, a butoxycarbonyl group, an isobutoxycarbonyl group, an S-butoxycarbonyl group or a t-butoxycarbonyl group, preferably a methoxycarbonyl group or an ethoxy group. A carbonyl group, particularly preferably a methoxycarbonyl group.

In the above, in the definition of R ³ and R ⁶ , “a C ₆ —C ₁₄ aryl group which may have 1 to 3 S substituents selected from the same or different substituent group A” Is an aromatic hydrocarbon group having 6 to 14 carbon violet numbers which may have the substituent, for example, a phenyl group, a fluorophenyl group, a difluorophenyl group, a cyclophenyl group, a dichlorophenyl group, and a bromophenyl group. Group, tolyl group, xylyl group, mesityl group, ethylphenyl group, cumenyl group, butylphenyl group, t-butylphenyl group, hexylphenyl group, fluoromethylphenyl group, difluoromethylphenyl group, trifluoromethyl group 2-methylfluorophenyl, 2,2-fluoroethylphenyl, 2,2-difluoroethylphenyl, 2,2,2—trifluoroethylphenyl, 5-fluorene Tylphenyl group, methoxyphenyl group, dimethoxyphenyl group, ethoxyfunyl group, propoxyphenyl group, butoxyphenyl group, 2-ethylethylbutoxyphenyl group, methoxymethylphenyl group, methoxylphenyl group, t-butoxy group Butylphenyl group, methylthiophenyl group, ethylthiophenyl group, brovirthiophenyl group, butylthiophenyl group, biphenylyl group, fluorobiphenylyl group, methylbiphenylyl group, naphthylphenyl group , Hydroxyphenyl group, mercaptophenyl group, aminophenyl group, diaminophenyl group, butoxyaminophenyl group, carboxyphenyl group, carboxymethylphenyl group, formylphenyl group, acetylphenyl group, methoxycarbonylphenyl group, force Rubamo Rufue group, Shianofuyuniru group, nitrophenyl group, Lee Ndeniru group, Fluoroindenyl group, chloroindenyl group, methylindenyl group, trifluoromethylindenyl group, methoxyindenyl group, methoxymethylindenyl group, butylthioindenyl group, phenylindenyl group, hydroxyindenyl group, melcabidoindenyl group, amide group Group, acetylindenyl group, cyanoindenyl group, nitronindenyl group, naphthyl group, fluoronaphthyl group, difluoronaphthyl group, chloronaphthyl group, dichloronaphthyl group, methylnaphthyl group, dimethylnaphthyl group, ethylnaphthyl group, butylnaphthyl group Rifluoronaphthyl group, methoxynaphthyl group, ethoxynaphthyl group, butoxynaphthyl group, hydroxynaphthyl group, mercapbutnaphthyl group, aminonaphthyl , Acetylnaphthyl group, cyanonaphthyl group, nitronaphthyl group, phenanthrenyl group, eodophenanthrenyl group, hexylphenanthrenyl group, butoxybutylphenanthrenyl group, aminophenanthrenyl group, butyrylphenylanthrenyl group, butoxybutyryl Phenanthrenyl group, levavamoyl phenanthrenyl group, nitrofenanthrenyl group, anthracenyl group, eodoanthracenyl group, hexylanethracenyl group, fluorinated hexyluanthracenyl group, carboxyanthracenyl group, butoxycarbonyl It may be a luan toracenyl group, a cyanoan toracenyl group or a ditroan toracenyl group, and the aryl group of R ³ is preferably halogen, C 1, -C alkyl, fluoromethyl, difluoromethyl, trifluoromethyl. Methyl, 2 —Fluoroethyl, 2,2 —Difluoroethyl, 2,2,2 — Trifluoroethyl, -C alkoxy, methoxymethyl, ethoxymethyl, methylthio, ethylthio, phenyl, 4-fluorophenyl, 4-methylphenyl, 4-methyl 1 to 3 members selected from the same or different selected from the group consisting of toxicoxy, hydroxyl, thiol, amino, acetylamino, carboxy, carboxymethyl, formyl, acetyl, methoxycarbonyl, ethoxycarbonyl, carbamoyl, cyano and nitro A phenyl group or a naphthyl group which may have a substituent, more preferably fluorine, chlorine, C t -C alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2 , twenty two - Riff Ruoroechiru one alkoxy, main Tokishimechiru, methylthio, full sulfonyl A phenyl group which may have 1 to 3 JB substituents, which may be the same or different from the group consisting of, 4-fluorophenyl, 4-methylphenyl, 4-methoxyphenyl, cyano and nitro, Even more preferably, a phenyl group, a fluorophenyl group, a chlorophenyl group, a difluorophenyl group, a dichlorophenyl group, a trifluoromethylphenyl group, a tril group, a xylyl group, a mesityl group, a methoxyphenyl group, a cyanophenyl. Or nitrophenyl group, particularly preferably phenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2,3-difluorophenyl, 2.4-difluorophenyl, 2 , 5-difluorophenyl group, 2,6-difluorophenyl group, 3,4-difluorophenyl group, 3,5- A difluorophenyl group, a 3,4-dichlorophenyl group, a p-tolyl group, a 3-trifluoromethylphenyl group, a 4-trifluoromethylphenyl group or a 2-methoxyphenyl group, which are very suitable. Are a phenyl group, a 2,3-difluorophenyl group, a 2,4-difluorophenyl group, a 2,5-difluorophenyl group or a 3,4-dichlorofunyl group, most preferably a phenyl group or Is a 2,4-difluorophenyl group. The aryl group of FT is preferably fluorine, salt purple, C 1 -C 4 alkyl, fluoromethyl, difluoromethyl, trifluormethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-to One to three B substituents selected from the group consisting of rifluoroethyl, monoalkoxy, methoxymethyl, methylthio, phenyl, 4-fluorophenyl, 4-methylphenyl, 4-methoxyphenyl, cyano and nitro A phenyl group, which may have a phenyl group, a 2-fluorophenyl group, a 3-fluorophenyl group, a 4-fluorophenyl group, a 2,3-difluorophenyl group, and a 2,4-difluorophenyl Group, 2,5-difluorophenyl group, 2,6-difluorophenyl group, 3.5-difluorophenyl group, 3,4 A -dichlorophenyl group, a p-tolyl group, a 3-trifluoromethylphenyl group, a 4-trifluoromethylphenyl group or a 2-methoxyphenyl group, and particularly preferably a phenyl group. In the above, “C, aralkyl group optionally having 1 to 3 substituents, which are the same or different from the following S-substituent group A,” in the definition of R ³ , refers to the substituent may also be the rc _e has - from 1-3 C aryl group ", the"(## - group bonded to C ₆ alkyl group ", for example, a benzyl group, Furuo port base Njiru group, difluoromethyl O-benzyl, trifluobenzyl, chlorobenzyl, dichlorobenzyl, trichlorobenzyl, bromobenzyl, methylbenzyl, dimethylbenzyl, trimethylbenzyl, Ethylbenzyl group, fluoromethylbenzyl group, difluoromethylbenzyl group, trifluoromethylbenzyl group, fluoroethylbenzyl group, difluoroethylbenzyl group, trifluoroethylbenzen Group, methoxybenzyl group, ethoxybenzyl group, methoxymethylbenzyl group, ethoxymethylbenzyl group, methylthiobenzyl group, ethylthiobenzyl group, phenylbenzyl group, fluorophenylbenzyl group, hydroxybenzyl group , Mercaptobenzyl, aminobenzyl, t-butoxycarbonylaminobenzyl, carboxybenzyl, carboxymethylbenzyl, formylbenzyl, acetylbenzyl, methoxycarbonylbenzyl, benzylamoyl benzyl , Cyanobenzyl, nitrobenzyl, diphenylmethyl, trityl, dimethoxytrityl, naphthylmethyl, fluoronaphthylmethyl, difluoronaphthylmethyl, chloronaphthylmethyl, dichloronaphthyl Methyl group, methylnaphthylmethyl group, dimethylnaphthylmethyl group ethylnaphthylmethyl group, indenylmethyl group, methylindenylmethyl group, methoxyindenylmethyl group, phenanthrenylmethyl group, bromophenanthrenylmethyl group, butylphenylenan Surenylmethyl group, trifluorene hexylphenanthrenylmethyl group, butoxyphenanthrenylmethyl group, anthracenylmethyl group, iodoanthracenylmethyl group, butylthioanthracenylmethyl group, phenylanthracenylmethyl group, aminoanthracenylmethyl group, Phenethyl group, fluorophenethyl group, difluorophenyl! Netyl group, chlorophenene group, dichlorophenethyl group, methylfunetyl group, trimethylphenethyl group, trifluorome Ruch i phenethyl group, main butoxy methylphenylpolysiloxane We phenethyl group, main Toki shell chill off energy butyl group, methylthio Phenethyl group, phenylphenethyl group, methoxyphenylphenyl group, hydroxyphenyl group, mercaptophenyl group, aminophenethyl group, t-butoxycarbonylaminophenethyl group, carboxyphenethyl group, carboxymethylphenethyl group , Formyl phenethyl, acetyl phenethyl, methoxycarbonyl phenethyl, sorbamoyl phenethyl, cyano phenethyl, nitrofene, naphthyl, fluoronaphthyl, chloro Mouth naphthylethyl group, butylthionaphthylethyl group, methoxyphenylnaphthylethyl group, benzylaminonaphthylethyl group, phenylpropyl group, fluorophenylbromoyl group, chlorophenylphenylpropyl group, dichlorophenyl Provir group, methyl Phenyl bromo, dimethyl phenyl propyl, trimethyl phenyl propyl, trifluoromethyl phenyl chloro, methoxy phenyl chloro, dimethyl phenyl chloro, butoxy phenyl chloro, butoxy butyl phenyl N-Propyl, Cyanophenyl-Propyl, Nitrophenyl-Probyl, Naphthyl-Propyl, Iodonaphthyl-Propyl, Hexylnaphthyl-Propyl, Bromo-Hexylnaphthyl-Propyl, Methoxynaphthyl-Propyl, To Xyloxy naphthyl butyl group, mercaptunaphthyl butyl group, acetyl naphthyl bromo group, phenylbutyl group, fluorophenylbutyl group, difluorophenylbutyl group, chlorophenylbutyl group, dichlorophenylbutyl group, Methylphenyl butyl, naphthyl butyl, trifluoromethyl naphthyl butyl, butyryl naphthyl butyl, phenyl naphthyl butyl, benzoylamino naphthyl butyl, butoxycarbonyl naphthyl butyl, indenyl benchyl Group, a fluorinated indenylpentyl group, a methylindenylpentyl group, an anthracenylhexyl group, a hexylanthracenylhexyl group, a levavamoylanthracenylhexyl group or a nitrolanthracenylhexyl group, and preferably a halogen atom. , C,

-C alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2—difluoroethyl, 2,2,2—trifluoromethyl, -C alkoxy, methoxymethyl, ethoxymethyl, methylthio, ethylthio, phenyl, 41 Fluorophenyl, 4-methylphenyl, 4-methoxy 1 to 3 substituents selected from the group consisting of cyphenyl, hydroxyl, thiol, amino, acetylamino, carboxy, carboxymethyl, formyl, acetyl, methoxycarbonyl, ethoxycarbonyl, carbamoyl, cyano and nitro A benzyl group or a phenethyl group, and more preferably, fluorine, chlorine, C, -C alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2.2-difluoroethyl, 2.2. , 2-DOO Rifuruoroechiru one C ₄ alkoxy, main Tokishimechiru, Mechiruchi O, phenyl, 4 one-fluorophenyl, 4 one-methylphenyl, 4-main Tokishifue sulfonyl, 1 is selected same or different from the group consisting of Shiano and nitro With three fi substitution groups A benzyl group, a benzyl group, a fluorobenzyl group, a cyclobenzyl group, a difluorobenzyl group, a dichlorobenzyl group, a trifluoromethylbenzyl group, A methylbenzyl group, a dimethylbenzyl group, a trimethylbenzyl group, a methoxybenzyl group, a cyanobenzyl group or a nitrobenzyl group, and particularly preferably a benzyl group.

In the above, in the definition of R ³ , “mono-C s —C“ arylamino group ”optionally having 1 to 3 B substituents, which are the same or different from the following substituent group A, is the same as defined above. “C _e —C ₁₄ aryl group optionally having 1 to 3 substituents, which are the same or different from the following E-substituted group A”, is a group bonded to an amino group, for example, phenylamino Group, fluorophenylamino group, difluorophenylamino group, chlorophenylamino group, dichlorophenylamino group, bromophenylamino group, tolylamino group, xylylamino group, mesitylamino group, ethylphenyl Amino group, cumenylamino group, butylphenylamino group, t-butylphenylamino group, hexylphenylamino group, fluoromethylphenylamino group, difluoromethylphenylamine Amino, trifluoromethylphenylamino, 2-fluoroethylphenylamino, 2,2-difluoroethylphenylamino, 2,2,2-trifluoroethyl Diphenylamino, 5-fluoropentylphenylamino, methoxyphenylamino, dimethoxyphenylamino, ethoxyphenylamino, broboxyphenylamino, butoxyf Enilamino group, 2— Ethylbutoxyphenylamino group, methoxymethylphenylamino group, methoxyethylphenylamino group, t-butoxybutylphenylamino group, methylthiophenylamino group, ethylthiophenylamine Mino group, brovirthiophenylamino group, butylthiophenylamino group, biphenylamino group, fluorobiphenylamino group, methylbiphenylamino group, naphthylphenylamino group, hydroxyphenylamino group, mercapb Triphenylamino group, aminophenylamino group, diaminophenylamino group, butoxyaminophenylamino group, carboxyphenylamino group, carboxymethylphenylamino group, formylphenylamino group, acetylphenylamino group , Methoxycarbonylphenylamino group, Rubamoylphenylamino, cyanophenylamino, nitrophenylamino, indenylamino, fluorinedenylamino, cloindenylamino, methylindenylamino, trifluoromethylindenylamino, methyl Toxinindenylamino group, methoxymethylindenylamino group, butylthioindenylamino group, phenylindenylamino group, hydroxyindenylamino group, mercaptoindenylamino group, aminoindenylamino group, acetylindenylamino group, cytylindenylamino group, cyanildenylaminoamino group Mino group, Fluoronaphthylamino group, Difluoronaphthylamino group, Black naphthylamino group, Dichloronaphthylamino group, Methylnaphthy Lamino, dimethyl naphthylamino, ethyl naphthylamino, butylnaphthylamino, trifluoronaphthylamino, methoxynaphthylamino, ethoxynaphthylamino, butoxynaphthylamino, Hydroxynaphthylamino group, mercaptonaphthylamino group, aminonaphthylamino group, acetylnaphthylamino group, cyanonaphthylamino group, nitronaphthylamino group, phenanthrenylamino group, Enanthrenylamino, hexylfurananthrenylamino, butoxybutylphenanthrenylamino, aminophenylphenanthrenylamino, butyrylphenanthrenylamino, t-butoxybutylphenanthr Nilamino group, Lilva moylphenanthrenylamino group, Nitrophenane Reniruamino group, Kishiruan Toraseniruami Anne tiger Seniruamino group, ® over Doan Bok Raseniruamino group to, Group, a fluorinated hexyl anthracenylamino group, a carboxyanthracenylamino group, a butoxycarbonylanthracenylamino group, a cyanoanthracenylamino group or a nitroanthracenylamino group, preferably a halogen, C, -C alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, C, -C * alkoxy, methoxymethyl, ethoxymethyl, methylthio, ethylthio , Phenyl, 4-fluorophenyl, 4-methylphenyl, 4-methoxyphenyl, hydroxyl, thiol, amino, acetylamino, carboxy, carboxymethyl, formyl, acetyl, methoxycarbonyl, ethoxycarbonyl, ethoxycarbonyl A phenylamino group or a 2-naphthylamino group, which may have 1 to 3 S substituents selected from the group consisting of moyl, cyano and nitro, which are the same or different, more preferably fluorine, chlorine, C _t -C alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2.2-difluoroethyl, 2,2,2-trifluoroethyl, -C * alkoxy, methoxymethyl, methylthio, phenyl, 4-fluorofur; Phenyl, 4-methylphenyl, 4-methoxyphenyl, cyano and nitro, which are the same or different and may have 1 to 3 substituents, and more preferably a fuunylamino group. Phenylamino, fluorophenylamino, black phenylamino, difluorophenylamino Group, dichlorophenylamino group, trifluoromethylphenylamino group, tolylamino group, xylylamino group, mesitylamino group, methoxyphenylamino group, cyanophenylamino group or nitrophenylamino group. Represents a phenylamino group or a 2,4-difluorophenylamino group.

In the definition of R ³ , "a 5-substituted or 6-substituted aromatic compound which may have one substituent selected from the following substituent group A, may be combined with a benzene ring, A purple ring group (the double purple ring contains one or two acid purple, nitrogen or sulfur atoms) ”is, for example, a pyrrolyl group, a fluoropyrrolyl group, a cyclopyrrolyl group, a methylpyrrolyl group, a methoxypyrrolyl group, Amyl biaryl group, methoxycarbonyl biaryl group, Imi Dazolyl, Fluoroymidazolyl, Chloroimidazolyl, Promoimidazolyl, Podoimidazolyl, Birazolyl, Methylpyrazolyl, Ethylbirazolyl, Provirvirazolyl, Butylpyrazolyl, Butoxybutylvillazolyl, Oxazolyl Group, fluoroxazolyl group, chloroxazolyl group, phenyloxazolyl group, methoxyphenyloxazolyl group, isoxazolyl group, cycloisoxazolyl group, hexolisoxazolyl group, phenyl Luisoxazolyl group, methoxyphenylisoxazolyl group, hydroxyiisoxazolyl group, melbutoysoxazolyl group, thiazolyl group, bromohexylthiazolyl group, hexoxyoxythiazolyl group, butoxybutylthiazolyl group, butylthio Thiazolyl group, futhiylthiazolyl group, isothiazolyl group, hydroxyiisothiazolyl group, mercaptoisothiazolyl group, aminoisothiazolyl group, benzylaminoisothiazolyl group, pyridyl group, fluoropyridyl group, chloropyridyl group, methylpyridyl group Group, ethyvililidyl group, trifluoromethyl viridyl group, methoxypyridyl group, ethoxypyridyl group, methoxymethyl viridyl group, methoxethyl viridyl group

, Methylthiopyridyl group, ethylthiopyridyl group, xylrubyridyl group, methoxyphenylpyridyl group, hydroxyviridyl group, mercapbutyridyl group, aminopyridyl group, butoxycarbonylaminobiridyl group, carboxybilidyl group , Carboxymethyl viridyl group, formylpyridyl group, acetyl viridyl group, methoxycarbyl viridyl group, cyano viridyl group, nitropyridyl group, virazinyl group, fluorovirazinyl group, chlorovirazinyl group, methylvirazinyl group, ethylpyrazinyl group , Trifluoromethyl virazinyl group, methoxy virazinyl group, ethoxy vilazinyl group, methoxymethyl virazinyl group, methoxethyl virazinyl group, methylthio virazinyl group, ethyl thio virazinyl group , Phenylvillage Nyl, tolyl virazinyl, hydroxy virazinyl, mercapto virazinyl, amino virazinyl, t-butoxycarbonylamino virazur, carboxyvirazinyl, carboxymethyl villazinyl, formyl virazinyl, acetyl villa Dinyl group, methoxycarbyl razil group, rubamoyl bilazinyl group, cyano virazinyl group, nitrobirazinyl group, birimidinyl group, bromobilimidinyl group , Hexylpyrimidinyl group, bromohexylpyrimidinyl group, hexyloxybilimidinyl group, viridazinyl group, butoxybutyl viridazinyl group, butylthioviridazinyl group, methoxyphenyl viridazinyl group, hydroxyviridazinyl group, ind Drill group, fluorinine drill group, black mouth drill group, methylindryl group, ethylindryl group, trifluoromethylindrill group, methoxyindryl group, methoxymethylindl Ryl group, Methylthioindryl group, Phenylindryl group, Hydroxyindrill group, Aminoindryl group, t-butoxycarbonylaminodrill group, Carboxyindrill group> Carboxymethylindrill group, Formyl indolyl group, acetylui Drill group, methoxycarbonylindryl group, carbamoylin drill group, cyanoin drill group, nitroin drill group, quinolyl group, fluoroquinolyl group, chloroquinolyl group, methylquinolyl group, ethylquinolyl group , Trifluoromethylquinolyl group, methoxyquinolyl group, ethoxyquinolyl group, methoxymethylquinolyl group, methoxyshetylquinolyl group, methylthioquinolyl group, phenylquinolyl group, hydroxyquinolyl group, mercaptoquinolyl group Group, aminoquinolyl group, benzylaminoquinolyl group, carboxyquinolyl group, carboxymethylquinolyl group, formylquinolyl group, acetylquinolyl group, methoxycarbonylquinolyl group, carbamoylquinolyl group, cyanoquinolyl group, nitroxyl group Ryl, indazolyl, promoindazolyl, odoindazolyl, hexylindazolyl, quinoxalinyl, bromopentylquinoxalinyl, hexyloxyquinoxalinyl, butoxybutylquinoxalinyl, butyi Luthioquinoxalinyl group, quinazolinyl group, phenylquinazolinyl group, methoxyphenylquinazolinyl group, hydroxyquinazolinyl group, aminoquinazolinyl group, benzoxazolyl group, benzoylaminobenzozoxazolyl group, carboxybenzozo Xazolyl group, carboxybutylbenzoxazolyl group, butyrylbenzoxazolyl group, benzisoxazolyl group, fluorobenzoisoxazolyl group, benzobenzoisoxazolyl group, methylbenzoisoxazolyl group, phenylbenzoisoxazolyl group, phenyl Base Nzoi Sokisazoriru group, off Lil group, fluoro furyl, black hole furyl group, a methyl off Lil group, Echirufu Lil group, preparative Riffle O b methylphenylpolysiloxane Lil group, main Bok Kishifu Lil group, Ethoxyfuryl, methoxymethylfuryl, ethoxymethylfuryl, methylthiofuryl, ethylthiofuryl, phenylfuryl, hydroxyfuryl, mercaptofuryl, aminofuryl, acetylaminofuryl, carboxyfuryl Group, carboxymethylfuryl, acetylfuryl, methoxycarbonylfuryl, carbamoylfuryl, cyanofuryl, nitrofuryl, benzofuranyl, hexylbenzofuranyl, bromohexylbenzofuranyl , Amino benzofuranyl group, carboxybutyl benzofuranyl group, butyryl benzofuranyl group, isobenzofuranyl group, hexyloxyisobenzofuranyl group, butoxybutylisobenzofuranyl group, trilui sorbenzofuranyl group, Benzylaminobenzobenzofuranyl group, butoxycarbonylisobenzofuranyl group, chenyl group, fluorochenyl group, chloro opening phenyl group, methyl phenyl group, ethyl phenyl group, trifluoromethyl phenyl group, methoxy phenyl group, ethoxy phenyl group , Methoxymethyl phenyl, ethoxymethyl phenyl, methyl thio phenyl, ethyl thio phenyl, phenyl phenyl, hydroxy phenyl, mercapto butyl, amino phenyl, acetyl amino phenyl, Carboxyphenyl, carboxymethyl phenyl, formyl phenyl, acetyl phenyl, methoxy carbonyl phenyl, carbamoyl phenyl, cyano phenyl, nitro phenyl, benzo phenyl, full It may be a benzobenzoenyl group, a chlorobenzobenzoyl group, a methylbenzophenyl group or an ethyl benzobenzoyl group, preferably a nodogen, C, -C alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluorethyl. , 2,2-Difluoroethyl, 2,2.2 —Trifluoroethyl, monoalkoxy, methoxymethyl, ethoxymethyl, methylthio, ethylthio, phenyl, 4-monofluorophenyl, 4-methylphenyl, 4-methoxyphenyl, hydroxyl, thiol, amino Pyrrolyl, which may have one g-substituent selected from the group consisting of acetylamino, carboxy, carboxymethyl, formyl, acetyl, methoxycarbonyl, ethoxycarbonyl, carbamoyl, cyano and nitro. Group, Pyridyl group, virazinyl group, pyrimidinyl group, viridazinyl group, indolyl group, quinolyl group, furyl group Or more preferably a phenyl group, more preferably fluorine, chlorine, monoalkyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, -C * alkoxy. A pyridyl group optionally having one substituent selected from the group consisting of methoxymethyl, methylthio, phenyl, 4-fluorophenyl, 4-methylphenyl, 4-methoxyphenyl, cyano and nitro, a virazinyl group , An indolyl group, a quinolyl group, a furyl group or a phenyl group, and more preferably, a 2-pyridyl group, a 3-pyridyl group, a 4-pyridyl group, a virazinyl group, a 3-methylvirazinyl group, a 1-methyl-2- Indolyl, 2-quinolyl, 3-quinolyl, 4-quinolyl, 2-furyl, 3- Furyl, 2-Chenyl, 3-Chenyl, 5-Fluoro-2-Chenyl, 5-Chloro-2-Cenyl, 3-Methyl-2-Cenyl, 5-Methyl-2-Cenyl, 3-Me Toxyl 2-phenyl, 5-fluoro-3-phenyl, 5-chloro-3-phenyl, 4-methyl-3-phenyl, 5-methyl-3-phenyl, 4-methyl-3-phenyl or 5-methoxy It is a methoxy-3-enyl group, particularly preferably a 3-pyridyl group, a virazinyl group, a 1-methyl-2-indolyl group, a 4-quinolyl group, a 2-furyl group, a 2-phenyl group, a 3-phenyl group. A phenyl group, a 5-chloro-2-phenyl group, a 3-methyl-2-phenyl group, a 5-methyl-2-phenyl group or a 4-methoxy-3-phenyl group, and most preferably, a virazinyl group or a 2-phenyl group. Ki, 3—Ceni Group, 5-chloro-2-phenyl, 3-methyl-2-phenyl, 5-methyl-2-phenyl or 4-methoxy-3-phenyl, most preferably a virazinyl group or a 2-phenyl group. Or a 5-methyl-2-phenyl group.

The compound (I) or (II) of the present invention can be converted into a corresponding pharmacologically acceptable salt by treating with an acid according to a conventional method. For example, compound (I) or (II) is treated with a corresponding acid for 5 to 30 minutes at room temperature in a solvent (for example, ethers, esters or alcohols, especially ethers), and the precipitated crystals are collected by tt. Or by distilling off the solvent under reduced pressure. Such salts include, for example, hydrofluoride, hydrochloride, hydrobromide, iodide violet, nitric acid Minerates such as salts, perchlorates, sulfates or phosphates: such as methanesulfonate, trifluoromethanesulfonate, ethanesulfonate, benzenesulfonate or p-toluenesulfonate Sulfonates: Carboxylates such as fumarate, succinate, citrate, tartrate, oxalate or maleate; or or amino acid salts such as glutamate or aspartate. It is preferably a mineral salt, especially a hydrochloride.

 The compound (I) or (II) of the present invention or a pharmacologically acceptable salt thereof may be left in the air or recrystallized to absorb or adsorb water, It may be a sum, and each of them or a mixture thereof is included in the present invention.

 The compound (I) or (II) of the present invention has an asymmetric carbon violet in the molecule, and there are stereoisomers each having an R configuration or an S configuration. Any mixture in any proportion is encompassed by the present invention.

 In the compound (I) or (II) of the present invention or a pharmacologically acceptable salt thereof, preferred compounds have a specific rotation of (1).

In the compound (I) or (II) of the present invention, preferred compounds are those having the general formula (I), and more preferably, R 'in the general formula (I) is A group having CO--R ³ or a group having the general formula (III), wherein R ¹ and R ² are formed together with the nitrogen atom to which they are bonded, and Is a group having the general formula (III) in which R ¹ and R ′ are formed together with the room purple atom to which they are bonded in the general formula (I).

 In the compound (I) or (II) of the present invention, preferred compounds are those wherein X is a methylene group.

 In the compound (I) or (II) of the present invention, preferred compounds are those wherein m is an integer of 2 to 4, and more preferred are those wherein m is an integer of 2 or 4. is there. In the compound (I) or (II) of the present invention, preferred compounds include

(1) R ³ force C, 1 -C alkyl group, 1 -methylhexyl group, 1 -ethyl benzyl group, 1 -bromobutyl group; cyclopentyl group, cyclohexyl group; c Rogen, -C alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2.2,2-trifluoroethyl, -C * alkoxy, methoxymethyl, ethoxymethyl, methylthio, ethylthio, Phenyl, 4-fluorophenyl, 4-methylphenyl, 4-methoxyphenyl, hydroxyl group, thiol, amino, acetylamino, carboxy, carboxymethyl, formyl, acetyl, methoxycarbonyl, ethoxycarbonyl, ethoxylcarbonyl, cyano and nitro A phenyl group or a naphthyl group, which may have 1 to 3 substituents selected from the group consisting of the same or different from each other; fluoroviolet, salt purple, C> -C alkyl, fluoromethyl, difluoromethyl, trifluryl Oromethyl, 2-f Fluoroethyl, 2,2-Difluoroethyl, 2,2,2-Trifluoroethyl, monoalkoxy, methoxymethyl, methylthio, phenyl, 4-fluorophenyl, 4-methylphenyl, 4-methoxyphenyl, cyano and Nitro A benzyl group which may have 1 to 3 S-substituents selected from the group consisting of the same or different; a cyclopentylamino group or a cyclohexylamino group; fluorine, chlorine, C, -C alkyl, fluoromethyl, Difluoromethyl, Trifluoromethyl, 2-Fluoroethyl, 2,2-Difluoroethyl, 2,2,2-Trifluoroethyl, 1 C * alkoxy, Methoxymethyl, Methylthio, Phenyl, 4-Fluorophenyl, 4-Methylphenyl, 4-Methoxyphenyl The same or different than the group consisting of A phenylamino group optionally having 1 to 3 substituents selected from the group consisting of: halogen, -C <alkyl>, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2. 2,2-Trifluoroethyl, C, -C alkoxy, methoxymethyl, ethoxymethyl, methylthio, ethylthio, phenyl, 4-fluorophenyl, 4-methylphenyl, 4-methoxyphenyl, hydroxyl, thiol, amino, acetylamino, A pyrrolyl group, a pyridyl group, a virazinyl group, which may have one protecting group selected from the group consisting of carboxy, carboxymethyl, formyl, acetyl, methoxycarbonyl, ethoxycarbonyl, carpamoyl, cyano and nitro; Group, pyrimidinyl group, pyridazi Group, India A compound having the general formula (I), which is a luyl group, a quinolyl group, a furyl group or a phenyl group;

(2) R ³ force; butyl group, isobutyl group, s-butyl group, t-butyl group, 1-ethylpentyl group; cyclobentyl group or cyclohexyl group; fluorine, salt purple,

C-Calkyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2—fluoroethyl, 2,2—difluoroethyl, 2,2.2—trifluoroethyl, C alkoxy, methoxymethyl, methylthio, phenyl, 4-fluorophenyl, 4-fluorophenyl A phenyl group which may have 1 to 3 substituents, which may be the same or different and is selected from the group consisting of methylphenyl, 4-methoxyphenyl, cyano and nitrogen; benzyl, fluorobenzyl and Benzyl group, difluorobenzoyl group, dichlorobenzyl group, trifluoromethylbenzyl group, methylbenzyl group, dimethylbenzyl group, trimethylbenzyl group, methoxybenzyl group, cyanobenzyl group, nitrobenzyl group; Cyclohexylamino group; phenylamino group, Fluorophenylamino, cyclophenylamino, difluorophenylamino, dichlorophenylamino, trifluoromethylphenylamino, triamino, xylylamino, mesitylamino, methoxyphenylamino Group, cyanophenylamino group or nitrophenylamino group; or fluorine, salt purple, C, -C alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2-difluoroethyl 1, 2 — trifluorofluoroethyl, -C alkoxy, methoxymethyl, methylthio, phenyl, 4-fluorophenyl, 4-methylphenyl, 4-methoxyphenyl, cyano and nitro A pyridyl group, a virazinyl group, a Drill group, quinolyl group, furyl group or thienyl group, compounds having the formula (I),

(3) R ³ force; t-butyl group, 1-ethylpentyl group, cyclohexyl group, phenyl group, fluorophenyl group, chlorophenyl group, difluorophenyl group, dichlorophenyl group, trifluoromethylphenyl Group, tolyl group, xylyl group, mesityl group, methoxyphenyl group, cyanophenyl group, nitrophenyl group, benzene Zyl group, phenylamino group, 2,4-difluorophenylamino group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, virazinyl group, 3-methylbirazinyl group, 1-methyl-2-y Drillyl group, 2-quinolyl group, 3-quinolyl group, 4-quinolyl group, 2-furyl group, 3-furyl group, 2-phenyl group, 3-phenyl group, 5-fluoro-2-phenyl group , 5-chloro-2-phenyl, 3-methyl-2-phenyl, 5-methyl-2-phenyl, 3-methoxy-2-phenyl, 5-fluoro-3-phenyl, 5-chloro-3-phenyl, 5-chloro-3-phenyl A compound having the general formula (ί), which is a 4-methyl-3-phenyl group, a 5-methyl-3-phenyl group, a 4-methoxy-3-phenyl group or a 5-methoxy-3-phenyl group,

(4) R ³ is phenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2,3-difluorophenyl, 2,4-difluorophenyl, 2,5-difluoro Phenyl group, 2,6-difluorophenyl group, 3,4-difluorophenyl group, 3,5-difluorophenyl group, 3,4-dichlorophenyl group, p-tolyl group, 3-trifluoromethyl Phenyl, 4-trifluoromethylphenyl, 2-methoxyphenyl, 3-pyridyl, virazinyl, 1-methyl-2-indolyl, 4-quinolyl, 2-phenyl Ryl, 2-Chenyl, 3-Chenyl, 5-Cross-2-Cenyl, 3-Methyl-12-Cenyl, 5-Methyl-2-Cenyl, or 4-Methoxy-3-Cenyl A compound having the general formula (I),

(5) R ³ is a phenyl group, a 2,3-difluorophenyl group, a 2,4-difluorophenyl group, a 2,5-difluorophenyl group, a 3,4-dichlorophenyl group, a birazinyl group, or a 2-phenyl group A general formula (I) which is a 3-, 3-phenyl, 5-chloro-2-phenyl, 3-methyl-2-phenyl, 5-methyl-2-phenyl or 4-methoxy-3-phenyl group; A compound having

(6) The compound having the general formula (I), wherein R ³ is a phenyl group, a 2,4-difluorophenyl group, a birazinyl group, a 2-phenyl group or a 5-methyl-2-phenyl group,

(7) R ¹ and R 'together with the nitrogen atom to which they are attached Kiso 3-thiazolidyl group, 5-mono C, -C * alkyl-1,2,4-dioxo-3-thiazolidyl group or 5,5-di-, -C * alkyl-1,2,4 dioxo-3 monothiazolidyl group or phthalimidyl group A compound having the general formula (I),

(8) R ¹ and 2, together with the nitrogen atom to which they are attached, are a 2,4-dioxo-3-thiazolidyl group, a 5-methyl-2,4-dioxo-3-thiazolidyl group, a 5,5-dimethyl-2, 4-Dioxo 3-thiazolidyl group, 5-methyl-5-ethyl-2,4-dioxo 3-thiazolidyl group, 5-ethyl-2,4-dioxo-1-thiazolidyl group, 5,5-Jethyl-2,4-dioxo 3- A compound having the general formula (I), which is a thiazolidyl group or a 5-isopropyl-12,4-dioxo-3-thiazolidyl group;

(9) R ¹ and R ² together with the nitrogen atom to which they are bonded, are 2,4-dioxo-3-thiazolidyl groups, 5,5-dimethyl-2,4-dioxo-3-thiazolidyl groups or 5- A compound having the general formula (I), which is isopropyl-1,4-dioxo-3-thiazolidyl group,

(10) R ¹ and R ² are, together with the nitrogen atom to which they are attached, a 5.5-dimethyl-2,4-dioxo-3-thiazolidyl group or a 5-isobrovir-12,4 dioxo-3-thiazolidyl group. A compound having the general formula (I),

(1 1) R ⁶ forces fluoride purple, salts purple, C, - C _lambda alkyl, Furuoromechiru, diphenyl Ruoromechiru, preparative Rifuruoromechiru, 2 Furuoroechiru, 2, 2-Jifuruoro Echiru, 2, 2, 2-preparative Rifuruoroechiru one C It may have 1 to 3 substituents selected from the same or different from the group consisting of alkoxy, methoxymethyl, methylthio, phenyl, 4-fluorophenyl, 4-methylphenyl, 4-methoxyphenyl, cyano and nitro A compound having the general formula (II), which is a phenyl group,

(1 2) R ^e is phenyl group, 2-fluorophenyl group, 3-Furuorofe group, 4 one fluorophenyl group, 2. 3-difluorophenyl group, 2, 4-di-fluorophenyl group, 2, 5- Difluorophenyl group, 2,6-difluorophenyl group, 3,5-difluorophenyl group, 3,4-dichlorophenyl group, A compound having the general formula (II), which is a luyl group, a 3-trifluoromethylphenyl group, a 4-trifluoromethylphenyl group or a 2-methoxyphenyl group;

1 3) a compound having the general formula (II), which is a R ⁶ group;

14) compounds wherein X is methylene,

 1 5) a compound wherein m is an integer of 2 to 4,

 1 6) a compound wherein m is 2

 1 7) a compound wherein m is 4;

It is also preferable to select 2 to 5 from the group of (1) (1) (13), (14) and (15) — (17) and to arbitrarily combine them. There are, for example, the following combinations.

 (18) (1) and (14),

 (1 9) (3) and (15),

 (20) (4), (14) and (15),

 (2 1) (5), (14) and (17),

 (22) (6), (14) and (17),

 (23) (7) and (14),

 (24) (8), (14) and (15),

 (25) (9), (14) and (15),

 (26) (10), (14) and (17),

(27) (13), (14) and (17).

Representative compounds of the present invention include, for example, the compounds described in the following table, but the present invention is not limited to these compounds.

 The abbreviations in the table are as follows.

 A c: acetyl

 B u ': tertiary butyl

 E t: ethyl

 2-Fur: Ruffles (2—)

 3-Fur: Frill (3—)

H ex ⁰ : cyclohexyl

 2-Ind: In Doll 2

 M e: Methyl

 P e n t: Pentyl

P ent ^c : Cyclobentil

 P h: Fanil

 P h t m: Phthalimidyl

 Pr: Pro Building

 P r ': Isoprovir

 2-Pyr: Pyridyl (2-)

 3-Pyr: Pyridyl (3—)

 4-Pyr: Pyridyl (4-1)

 P y z: Virazinyl (2-)

 2-Q u i n: one quinoline

 3-Q u i n: 3-quinoline

 4-Q u i n: 1-quinoline

 2-T h i: Chenil (2—)

 3-T h i: Chenil (3—)

T hiz: 2, 4-dioxothiazolidine-1-yl 【table 1】

Compound number R ³ X m

1-1 Me -CH _2-4

1-2 Et 4

1-3 Pr -CH _2-4

1-4 Bu ^l 2

1-5 Bu ^l 3 o

33 as cc

1-7 Bu ^l -0- 2

1-8 Bu ^l -0- 3

1-9 Βι -0- 4

1-10 1-Et-Pent 2

1-11 1-Et-Pent -CH _2-4

1-12 1-Et-Pent -0- 2

1-13 1-Et-Pent -0- 4

1-14 2-Et-Pent 2

1-15 2-Et-Pent 4

1-16 Pent ^c

Two

1-17 Pent ^c -CH _2-4

1-18 Hex ^c -CH ₂ - ₂

1-19 Hex "3

1-20 Hex ⁰ 4 ud 68 u 96

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5i -161 3-CN-Ph • CH 2 - 2

_{-162 3- CN-Ph • CH 2} - 4

_{-163 4- CN-Ph -CH 2 -} 2

-164 4-CN-Ph ■ CH 2 - 3

-165 4-CN-Ph -CH _2-4

-16 & 4-CN-Ph -0- 2

-167 4-CN-Ph -0- 4

_{-168 2-N0 2 -Ph -CH 2} - 2

-169 2- N0 ₂ -Ph -CH _2-4

_{-170 3- N0 2 -Ph ■ CH 2} - 2

_{-172 4- N0 2 -Ph -CH 2 -} 2

_{-173 4-N0 2 -Ph • CH} 2 - 3

-174 4-N0 ₂ -Ph -CH _2-4

-175 4-N0 ₂ -Ph -0- 2

-176 4-N0 ₂ -Ph -0- 4

-177 Pent '-amino -CH ₂ - ₂

-178 Pent ^c -amino -CH _2-4

-179 Hex ° -amino -CH ₂ - ₂

-180 Hex ^c -amino -CH ₂ - 3

-181 Hex ° -araino -CH _2-4

-182 Hex ^c -amino -0- 2

-183 Hex-ami no -0- 4

-184 Ph-amino -CH ₂ - ₂

-185 Ph-amino -CH ₂ - 3

-186 Ph-amino -CH _2-4

-187 Ph-amino -0- 2

-188 Ph-amino -0- 4 -189 2-F-Ph-amino -CH 2 - 2 1-190 2-F-Ph-amino -CH 2 - 4 1-191 3-F-Ph-ataino -CH 2 - 2 1-192 3-F -Ph-amino 2 1-193 3-F -Ph-amino 4 1-194 4-F-Ph - amino -CH 2 - 2 1-195 4-F-Ph-amino

4 1-196 2-Cl-Ph- amino -CH 2 - 2 1-197 2-Cl-Ph-amino 4 i- 3-Cl-Ph-amino -CH 2 - 2

1-199 3-Cl-Ph-amino 4

1-200 4-Cl-Ph-amino 2

1-201 4-Cl-Ph-amino 3

1-202 4-CI-Ph-amino 4

1-203 2, 3-diF-Ph-amino o PC 2

1-204 2 3-diF-Ph - amino -CH 2 - 3

1-205 2, 3-diF-Ph-amino 4

1-206 2, 4-diF-Ph-amino 2

1-207 2 4-diF-Ph-amino 3

1-208 2 4-diF-Ph-amino -CH _2-4

1-209 2, 4-diF-Ph-amino -0- 2

1-210 1, 4-diF-Ph-amino -0- 4

1-211 3 4-diF-Ph- amino -CH 2 - 2

_{1-212 Z t 4-diF-Ph} -amino -CH 2 - 3

1-213 3, 4-diF-Ph-amino -CH _2-4

1-214 2 3-diCl-Ph-amino -CH,-2

1-215 2, 3-diCl-Ph -amino -CH 3 - 3

1-216, 3-diCl-Ph-amino 4 -217 2, 4-diCl -Ph- amino -CH 2 - 2-218 2, 4-diCl-Ph-amino 3-219 2.4-diCl-Ph-amino -CH 2 - 4-220 2, 5-diCl- Ph-amino 2-221 2, 5- diCl-Ph-amino -CH 2 - 3-222 2, 5-diCl-Ph-amino

4-223 2-Me-Ph-amino -CH 2 - 4-224 3-Me-Ph-amino -CH 2 - 2-225 3-Me-Ph-amino -CH 2 - 4-226 4-Me-Ph -amino 4-227 2-MeO-Ph- amino -CH 2 - 2-228 2-MeO-Ph-amino

4-229 3-MeO-Ph-amino 4-230 4-MeO-Ph-amino BS 4-231 l-Me-2-Ind 2-232 l-Me-2-Ind 3-233 l-Me-2- Ind -CH _2-4

-235 l-Me-2-Ind-0-4-236 2-Pyr 2-237 2-Pyr 3-238 2-Pyr 4-239 3-Pyr 2-240 3-Pyr 3-241 3-Pyr -CH _{2 - 4-242 3-Pyr -0- 2-243} 3-Pyr -0- 4-244 4-Pyr 2 - ^£ H3- lLZ- \

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8E dT / X3d 68m £ 96 OAi _{-273 3-Fur -CH 2 - 1-274} 3-Fur -CH 2 - 4-275 3-F-3-Fur -CH 2 - 2-276 3-F-3-Fur -CH 2 - 4-277 5-F-3-Fur -CH 2 - 2-278 5-F-3-Fur -CH 2 - 4-279 5-Me-3-Fur -CH 2 - 2

-281 5 - MeO - 3 - Fur -CH 2 - 2-282 5-MeO-3-Fur -CH 2 - 4

_{-285 2-Thi -CH 2 - 4-286} 2-Thi -0- 2-287 2- Thi -0- 4-288 3- F-2-Thi -CH 2 - 2-289 3-F-2- Thi -CH, - 3-290 3-F -2-Thi -CH 2 - 4-291 5-F-2-Thi ■ CH 2 - 2-292 5-F-2-Thi -CH 2 - 3-293 5-F-2-Thi -CH 2 - 4-294 3-Cl-2-Thi -CH 2 - 2-295 3-Cl-2-Thi -CHs- 3-296 3-Cl-2-Thi ■ CH _{2 - 4-297 5-Cl-2} -Thi -CH 2 - 2-298 5-Cl-2-Thi ■ CH 2 - 3-299 5-Cl-2-Thi -CH¾- 4-300 5-Cl- 2-Thi ■ 0- 2

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2-16 5-Me-Thiz -0- 4

2-17 5-Me-Thiz -0- 5

_{2-18 5-Et-Thiz -CH 2} - 2

_{2-19 5-Et-Thiz -CH 2} - 3

2-20 5-Et-Thiz -CH _2-4

_{2-21 5-Et-Thiz -CH 2} - 5

2-22 5-Et-Thiz -0- 2

2-23 5-Et-Thiz -0- 4

2-24 5-Et-Thiz -0- 5

_{2-25 5.5-diMe-Thiz -CH 2} - 2

2-26 5, 5-diMe-Thiz -CH 2 - 3

2-27 5.5-diMe-Thiz -CH _2-4

_{2-28 5.5-diMe-Thiz -CH 2} - 5

2-29 5, 5-diMe-Thiz -0- 2

2-30 5, 5-diMe-Thiz -0- 4

2-31 5, 5-diMe-Thiz -0- 5

_{^{2-32 5-Pr l -Thiz -CH 2}} - 2

2-34 5-Pr'-Thiz -CH _2-4

_{^{2-35 5-Pr l -Thiz -CH 2}} - 5

2-36 5-Pr ^l -Thiz -0- 2

2-37 5-Pr'-Thiz -0- 4

_{2-38 e-Bu ^ Thiz -CH 2} - 2

2-40 S-Bu'-Thiz -CH _2-4

_{^{2-41 5-Bu l -Thiz -CH 2}} - 5

2-42 S-Bu'-Thiz -0- 2

2-43 5-Bu ^l -Thiz -0- 4

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5, 5-diBu ^l -Thiz -0- 2

3-18 3- F-Ph -0- 4

_{3-19 4- F-Ph -CH 2 -} 2 -20 4-F-Ph -CH 2 - 3 -21 4-F-Ph -CH 2 - 4 -22 4-F-Ph -0- 2 -23 4-F-Ph -0- 4 -24 2,3-diF-Ph -CH 2 - 2 -25 2,3-diF-Ph -CH 2 - 3 -26 2, 3-diF-Ph -CH 2 - 4 -27 2, 3-diF- Ph -0- 2 -28 2.3- diF-Ph -0- 4 -29 2.4- diF-Ph -CH 2 - 2 -30 2,4-diF-Ph -CH 2 - 3 -31 2,4-diF-Ph -CH _2-4 -32 2,4-diF-Ph -0- 2-33 2.4- diF-Ph -0- 4-34 2.5- diF-Ph -CH _2- 2-35 2, 5-diF-Ph -CH 2 - 3-36 2.5- diF-Ph -CH 2 - 4-37 2.6- diF-Ph -CH 2 - 2-38 2, 6-diF-Ph -CH _{2 - 3-39 2, 6-diF} -Ph -CH 2 - 4

-41 3, 5-diF-Ph -CH 2 - 3-42 3.5-diF-Ph -CH 2 - 4-43 2-Cl-Ph -CH 2 - 2-44 2-Cl-Ph -CH 2 - 3 -45 2-Cl-Ph -CH _2-4 0061 / 9- 6896

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_{3-130 4-N0 2 -Ph ■ 0-} 3-131 4-NO Ph -0- Kisahi Dorobirajinokino phosphorus derivative conductor to have the general formula (I) or (II) of the present invention [formula (I a), ( In (I) and (II)], preferred compounds include 6, 1-7, 1-11, 1-13, 1-17, 1-20, 1-123, 1-11 twenty four,

1-125, 1-128, 1-30, 1-13-1, 1-133, 1-136, 1-337-1, 39, 1-141, 1-142, 1-144, 1-147 , 1-148, 1-150, 1-15 2, 1-153, 1-155, 1-158, 1-160, 1-16-1, 1-163, 1-165, 1 — 66, 1 — 6 8, 1-70, 1-7 1, 1-7 3, 1-75, 1-77, 1-79, 1-81, 1-82, 1-83, 1-84, 1 1-85, 1-86, 1-87, 1-88, 1-89, 1-90, 1-9-1, 1-92,-1 05, 1-107, 1-109, 1- 1 1-1 1 4-1 1 5 7, 1 1 1 8, 1-1 1 9, 1-1 2 1 1 24-1 2 9-1 3 1 1 3 6, 1-1 37, 1-1 3 1 1 4 1-1 47-1 60, 1 1 62, 1 1 63, 1-1 6-1 69-1 74, 1 1 7 8, 1-1 7 9, 1-1 8 -1 84 — 1 86, 1 1 90,

-1 9 3.1-1 9 5.1 1 1 9 1 1 9 9-2 02,-2 0 5, 1 2 06, 1-2 08, 1-2 1-2 1 6-2 1 9, -2 2 2, 1 2 3 1, 1-2 3 3, 1-2 3-2 39-24 1,-245, 1 246, 1 248, 1-2 5-2 54-2 55,-2 5 7, 1 2 60, 1-2 62, 1-28-2 85 — 288.-2 9 1 2 93, 1 — 2 97, 1-2 9 1 3 0 2 — 304,-3 0 7, 1 3 0 9, 1 — 3 1 4, 1-3 1-3 1 7 — 32 0,-32 2, 1 34 3, 1 — 345, 1-35 1 356 — 359.-36 3, 1 3 6 5 , 2—1, 2—2, 2—2—4, 25, 2—2 5 2—2 7>

2-28, 2-32, 2-33, 2-34, 2-35, 2-40, 2-41, 2-44, 2-45, 2-46, 2-47, 2 -48, 3-1, 3-2, 3-3,

3-4, 3-11, 3-16, 3-21, 3-4 5, 3-50, 3-55.3- 60, 3-65, 3-70, 3-7 3.3-75, 3-78, 3-83 or 3-88.

 More preferred compounds include 1-6, 1-11, 1-20, 1-23, 1-12

4 1-2 5.30, 1-33 39, 1 — 44, 1 1 50, 1-5 3

5 5, 1 1 6 3, 1 1 68, 1 1 73, 1 1 7 9, 1-92-1 1 1 1 1 1 9, 1-1 24, 1-1 3 1 1 39, 1 1 1 47 -1 6 5

— 1 74, 1 — 1 8 1, 1-1 86 2 08, 2 33-2 4 1 1 2 48, 1-2 57. 1-2 62 1 1 2 83, 285-2 99

— 30 2, 1 — 3 04, 1-307 309, 1 343-345 1 3 6 5, 2 — 2, 2-3, 2-4 2 — 27, 2 — 34, 2 — 46 or 3 1 3 Can be mentioned.

 Particularly preferred compounds are 1-23, 1 25, 1 50, 1 55, 1-63, 1-92, 1-248, 1-283.1-285, 1-299, 1 -30 2, 1-30 9, 1-343, 1-345, 1-365, 2-27 or 2-34.

 The most preferred compounds include

 Compound No. 1 2 3: 3-(2-benzamidoethyl) 1, 2,3,4.4a, 5,6-hexahi draw 1H-Virazino [1,2, -a] quinoline,

 Compound No. 1 2 5: 3-(4-benzamide butyl) 1, 2,3,4,4a, 5,6-hexahi draw 1H-Virazino [1,2, -a] quinoline,

 Compound No. 1 55: 3— [4- (2,4-difluorobenzamide) butyl] 1,2,3,4,4a, 5,6—Hexahi draw 1 H—Virazino [1, 2—a] quinoline,

 Compound No. 1 2 48: 3— [4- (2-Virazinecarbonylamino) butyl] 1,2,3,4,4a, 5,6-Hexahi draw 1 H—Virazino [1,2— a] quinoline,

Compound No. 1 — 285: 3— [4- (2-tenolamino) butyl] 1,2,3,4,4a.5.6—Hexahi Draw 1 H—Virazino [1.2—a] Kinori ,

 Compound No. 11-309: 3- [4- (5-methylthiophene-2-carbonylamino) butyl] 1,2,3,4,4a, 5,6-hexahidraw 1H-birazino [1,2 — A] Quinoline,

 Compound No. 2—27: 3— [4- (5,5-dimethyl-2,4-dioxothiazolidine-13-yl) butyl] 1,2,3,4,4a, 5,6 hexaldehyde One 1 H—birazino [1,2—a] quinoline or

 Compound No. 2—34: 3— [4- (5-Isobrovir-1,2,4-dioxothiazolidine-1-yl) butyl] —1,2,3,4,4a, 5.6—Hexahydro-1H— Virazino [1.2-a] quinoline. The method for producing the compound of the present invention is shown below.

(Method A)

 Step A 1

Y- (CH ₂ ) _m -Y HN-R ¹ Y— (CH ₂ ) χη- -R ¹

 R2 R2

(V) (VI) (VII)

(I) (Method B) 2) _m- NH _:

 (lb)

 R3CO-Y (X)

 Step B 2

 Or

R 3 COOH (XI) CK ₂ ) _m -NHCOR3

 (la)

(Method C)

Y— (CH ₂ ) _m -COY '(xii)

 Step C 1

Or H ₂ N-R6 Y— (CH ₂ ) _m — CONHR ⁶

Y— <CH ₂ ) _m -COOH (XIII)

 (XIV) (XV)

Step C 2

/)-NN— (CH ₂ ) _m -C0NHR6

(ID (Method D)

Step D 2

Step D 5

(VIII: In the above formula, R ′, R ² , R ³ , R ⁶ , X and m have the same meaning as described above, R ⁷ represents a C, — ， ₈ aralkyl group, and R ^e represents R ⁹ represents a C, -C alkoxycarbonyl group which may be replaced by a trigen or tri-C alkylsilyl, R ⁹ represents a halogen atom, and Y and Y 'represent the same or different leaving groups. Shown.

“C ₇ —C _<e aralkyl group” of R ^{7 has} the same meaning as described above, and examples thereof include a benzyl group, an α-phenethyl group, a 0-phenethyl group, a 3-phenylpropyl group, a 4-phenylbutyl group, and an α-phenyl group. —Naphthylmethyl group, / 3—naphthylmethyl group, 1- (α-naphthyl) ethyl group, 1- (0-naphthyl) ethyl group, diphenylmethyl group, trifluoromethyl group, α-naphthyldiphenylmethyl group or 91-anthuri And preferably a benzyl group or an α-phenethyl group, particularly preferably an α-phenethyl group.

"Halogen or Application Benefits C of R ^8, - at C alkylsilyl may be IB conversion, C -! C alkoxycarbonyl group, for example, main butoxycarbonyl group, Etoki aryloxycarbonyl group, Bro Po alkoxycarbonyl group, Isopurobo Oxycarbonyl group, butoxycarbonyl group, isobutoxycarbonyl group, s-butoxycarbonyl group, t-butoxycarbonyl group, chloromethoxycarbonyl group, 2,2,2-trichloromouth ethoxycarbonyl group, 2-fluoroborobo Xycarbonyl group, 2-bromo-t-butoxycarbonyl group, 2,2-dibutene-butoxycarbonyl group, triethylsilylmethoxycarbonyl group, 2-trimethylsilylethoxycarbonyl group, 4-triprovirsilyl Butoxycarbonyl group or t-butyldimethylsilylpropoxycarbonyl group And is preferably a methoxycarbonyl group, an ethoxycarbonyl group or a t-butoxycarbonyl group, particularly preferably a t-butoxycarbonyl group.

The halogen atom for R ⁹ has the same meaning as described above, and is preferably a salt purple atom or an odor purple atom.

The leaving group for Y and Y ′ is not particularly limited as long as it is a group capable of leaving as a nucleophilic residue. For example, a halogen atom such as salt purple, odor purple or iodine purple: methanesulfonyl A C, -C alkanesulfonyloxy group such as methoxy, ethanesulfonyloxy, propanesulfonyloxy or butanesulfonyloxy; trifluoromethansulfonyloxy, 2,2,2-trichloroethanesulfonyloxy, 3,3 Halogeno, such as, 3-, 3-bromopropanesulfonyloxy or 4.4,4-trifluorobutanesulfonyloxy; -C alkanesulfonyloxy group; or benzenesulfonyloxy, α-naphthylsulfonyloxy C,-, such as xy, | 3-naphthylsulfonyloxy, ρ-toluenesulfonyloxy, 4-t-butylbenzenesulfonyloxy, mesitylenesulfonyloxy or 6-ethyl-α-naphthylsulfonyloxy Cs—C. Which may have 1 to 3 C alkyl groups. Arylsulfonyloxy group, preferably chlorine, bromine or iodine atom; methanesulfonyloxy group or ethanesulfonyloxy group; trifluoromethanesulfonyloxy group, 2,2,2-trichloro A mouth ethanesulfonyloxy group or a pentafluoroethanesulfonyloxy group; or a benzenesulfonyloxy group, a Ρ-toluenesulfonyloxy group or a mesitylenesulfonyloxy group, more preferably chlorine or odor. It is a purple or iodine atom.

 The compound having the general formula (VI) and the compound having the general formula (VIII), which are the starting material compounds of the present invention, are known compounds or can be produced according to known methods. [For example, Journal of Medicinal Chemistry, Vol. 13, pp. 5 16 (1970) [J. Med. Chem., 13, 516 (1970) .1, Indian Journal 'Ob' Chemistry. Volume 7, p. 833 (1969) [Indian J. Chem .. 7.833 (1969).], Indian Journal of Ob. Chemistry, Vol. 13, 4 62 (1975) [Indian J. Chem., 13, 462 (1975).], US Pat. No. 4,367,335, Helvetica 'Hemika. Acta, Volume 20, page 1388 (1937) 1) [1 vesica Chimi Act, 0.1388 (1937).], Japanese Patent Application Laid-Open No. 50-58324, Japanese Patent Publication No. 46-33032, etc.].

 Method A is a method for producing compound (I).

Step A1 involves reacting a compound having the general formula (V) with a compound having the general formula (VI) in an inert solvent in the presence or absence (preferably in the presence) of a base. Is a step of producing a compound having the general formula (VII).

 The solvent used is not particularly limited as long as it does not hinder the reaction and dissolves the starting materials to some extent.For example, aliphatic hydrocarbons such as hexane, hebutane, lignin or petroleum ether Aromatic hydrocarbons such as benzene, toluene or xylene; halogenated hydrocarbons such as methylene chloride, carbonaceous form, carbon tetrachloride purple, dichloroethane, chlorobenzene or dichlorobenzene; Ethers such as isopropyl ether, tetrahydrofuran, dioxane, dimethoxetane or diethylene glycol dimethyl ether; amides such as formamide, dimethylformamide, dimethylacetamide or hexamethylphosphate triamide; or Dimethyl sulfoxide or sulfo It can be a sulfoxide such as an orchid, preferably an ether, an amide or a sulfoxide, more preferably an ether (especially getyl ether or tetrahydrofuran) or an amide ( Particularly, dimethylformamide).

The base used is, for example, an alkali gold carbonate such as sodium carbonate, potassium carbonate or lithium carbonate; an alkali metal such as sodium carbonate purple, sodium carbonate carbonate or lithium carbonate purple. Bicarbonates; Al hydrides such as lithium hydride, water purple sodium hydride or hydride hydride Gold hydrides: Al hydrides such as sodium hydroxide, hydration power or lithium hydroxide Alkali gold I »alkoxides such as sodium methoxide, sodium ethoxide, potassium t-butoxide or lithium methoxide; methyl mercaptan sodium or ethyl mer Merkabutane alkali metals such as sodium butane; triethylamine, tributylamine, diisoprovirethylamine, N— Tyl morpholine, pyridine, 4- (N, N-dimethylamino) pyridine, N, N-dimethylaniline, N.N-getylaniline, 1,5-diazabicyclo [4.3.0] nona-1-ene, 1. Organic amines such as 4-diazabicyclo [2.2.2] octane (DABC 0) or 1,8-diazabicyclo [5.4.0] pendequat 7-ene (DBU): methyllithium, ethyllithium or butyllithium Alkyllithium such as; lithium diisopropylamide or lithium diisopropyl It can be a lithium alkyl amide such as cyclohexyl amide, preferably, alkali gold bicarbonates, alkali metal bicarbonates, alkali gold bihydrides (particularly sodium purple violet). And alkali gold alkoxides or alkyllithiums, and more preferably alkali gold carbonates (sodium carbonate or potassium carbonate).

 The reaction temperature varies depending on the starting compound, the reagent, the solvent and the like, but is usually from 120 to 100, preferably from 0 to 50.

 The reaction time varies depending on the starting compound, reagent, solvent and reaction temperature, but is usually 10 minutes to 12 hours, preferably 30 minutes to 5 hours.

After completion of the reaction, the target compound of this step is collected from the reaction mixture according to a conventional method. For example, after the reaction is completed, water is added to the reaction solution, a solvent immiscible with water (eg, benzene, ether, ethyl acetate, etc.) is added to extract the target compound, and the extracted organic layer is washed with water, and then anhydrous magnesium sulfate, etc. And the solvent is distilled off to obtain the desired compound. The obtained target compound can be further purified, if necessary, by a conventional method, for example, recrystallization, reprecipitation, chromatography, or salt formation by adding an acid. The step A2 comprises reacting the compound having the general formula (VII) with the compound having the general formula (VIII) in an inert solvent in the presence or absence (preferably in the presence) of a base. To produce a compound having the general formula (I). The solvent used is not particularly limited as long as it does not hinder the reaction and dissolves the starting materials to some extent. Examples thereof include aliphatic hydrocarbons such as hexane, heptane, rigoin or petroleum ether; Aromatic hydrocarbons such as benzene, toluene or xylene; Halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene or dichlorobenzene; Ethers such as virether, tetrahydrofuran, dioxane, dimethoxetane or diethylene glycol dimethyl ether; alcohols such as methanol, ethanol, propanol, isopropanol, butanol or isobutanol; formamide, dimethylformamide, Amides such as dimethyl acetate or hexamethyl phosphate triamide; It may be a sulfoxide such as tyl sulfoxide or sulfolane, preferably an ether, an alcohol or an amide, and more preferably an alcohol (particularly isopropyl alcohol or butanol).

 The base used is, for example, an alkali metal carbonate such as sodium carbonate, potassium carbonate or lithium carbonate; an alkali metal such as sodium carbonate purple, sodium carbonate carbonate or lithium hydrogencarbonate. Bicarbonates; Al hydrides such as lithium hydride, sodium violet or hydrogen hydride Gold hydrides: Al hydrides such as sodium hydroxide, hydroxyl hydride or lithium hydroxide Alkali metal hydroxides; Alkali metal alkoxides such as sodium methoxide, sodium ethoxide, potassium t-butoxide or lithium methoxide; Such as methyl mercaptan natrium or ethyl mercaptan natrium Merkabutane alkali metals; triethylamine, tributylamine, diisoprovirethylamine; N-meth Tyl morpholine, pyridine, 4- (N, N-dimethylamino) pyridine, N, N-dimethylaniline, N, N-getylaniline, 1,5-diazabicyclo [4.3.0] nona-1-ene, 1. Organic amines such as 4-diazabicyclo [2.2.2] octane (DABC 0) or 1,8-diazabicyclo [5.4.0] pendec 7-ene (DBU); methyllithium, ethyllithium or butyllithium Or lithium alkyl amides such as lithium diisopropyl amide or lithium dicyclohexyl amide; preferably, alkali metal alkoxides or alkali metal hydrides. And more preferably alkaline gold carbonates (particularly sodium carbonate or potassium carbonate).

 The anti-15 temperature varies depending on the starting compound, reagent, solvent and the like, but is usually from 0 to 150, preferably from 20 to 100 * C.

 The reaction time varies depending on the starting compound, reagent, solvent and reaction temperature, but is usually 30 minutes to 24 hours, preferably 1 hour to 12 hours.

After completion of the reaction, the target compound of this step is collected from the reaction mixture according to a conventional method. For example, remove any insoluble matter and remove the solvent, or distill off the solvent, or add water to the residue from which the solvent has been distilled off, and add a water-immiscible solvent (eg, benzene, ether). , Ethyl acetate, etc.) to extract the target compound, wash the extracted organic JB with water, dry over anhydrous magnesium triluate, etc., and distill off the solvent to obtain the target compound. The obtained target compound can be further purified, if necessary, by a conventional method, for example, recrystallization, reprecipitation *, chromatography, or salting with an acid.

Method B, At a compound (I), R ¹ is a method of producing compound is a group having the formula one COR ³ and (I a).

Step B1 is a compound having the general formula (I) obtained by Method A, wherein R ¹ and R ² form a phthalimidyl group together with the nitrogen atom to which they are bonded (lb). By reacting with a base in an inert solvent, the general formula

This is a step of producing a compound having the formula (I X).

 The solvent used is not particularly limited as long as it does not hinder the reaction and dissolves the starting materials to some extent.For example, aliphatic hydrocarbon purples such as hexane, heptane, rigoin or petroleum ether Aromatic hydrocarbons such as benzene, toluene or xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene or dichloromethane, etc .; Ethers such as diisopropyl ether, tetrahydrofuran, dioxane, dimethoxetane or diethylene glycol dimethyl ether; alcohols such as methanol, ethanol, propanol, isopropanol, butanol or isobutanol; formamide, dimethylformamide Do Amides such as dimethylacetamide or hexamethylphosphate triamide; or sulfoxides such as dimethylsulfoxide or sulfolane, preferably alcohols or amides, more preferably alcohols (Especially methanol or ethanol).

 The base used can be, for example, hydrazines such as hydrazine or hydrazine hydrate or organic amines such as methylamine, ethylamine or butylamine, preferably hydrazines (especially hydrazine hydrate). Drazine).

The reaction temperature varies depending on the starting compound, the reagent, the solvent and the like, but is usually 0 to 150 \ :, preferably 20 to 100 ^. The reaction time varies depending on the starting compound, reagent, solvent and reaction temperature, but is usually 30 minutes to 24 hours, preferably 1 hour to 12 hours.

 After completion of the reaction, the target compound of this step is collected from the reaction mixture according to a conventional method. For example, remove any insoluble matter and remove the solvent, or distill off the solvent, or add water or alkaline water to the residue from which the solvent has been distilled off, and add a water-immiscible agent (eg, benzene). , Methylene chloride, ether, ethyl acetate, etc.) to extract the target compound, wash the extracted organic layer with water, dry over anhydrous magnesium triluate, etc., and distill off the solvent to obtain the target compound. The desired compound obtained can be further purified, if necessary, by a conventional method, for example, recrystallization, reprecipitation, chromatography or salt formation by adding an acid.

 In the step B2, a compound having the general formula (I X) is

 (a) reacting with a compound having the general formula (X) in an inert solvent in the presence or absence (preferably in the presence of a base) of a base, or

 (b) by reacting with a compound having the general formula (I) in an inert solvent in the presence of a condensing agent (if necessary, in the presence of a base),

This is a step of producing a compound having the general formula (la).

The solvent used in the step B2a is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent, and examples thereof include hexane, heptane, ligroin and petroleum ether. Aliphatic hydrocarbons; Aromatic hydrocarbons such as benzene, toluene or xylene; Halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, cyclobenzene or dichlorobenzene Ethers such as getyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxetane or diethylene glycol dimethyl ether; amides such as formamide, dimethylformamide, dimethylacetamide or hexamethylphosphate triamide Class: Or dimethyl sulfoxide Obtained is de or sulfoxides such as sulfolane, preferably a halogenated hydrocarbon violet acids or ethers, more preferably ethers (particularly Jefferies chill ether or Te Torahi Dorofuran). The base used is, for example, an alkali gold carbonate such as sodium carbonate, potassium carbonate or lithium carbonate; an alkali metal such as sodium carbonate purple, sodium carbonate carbonate or lithium carbonate purple. Bicarbonates; Al hydrides such as lithium hydride, water purifying sodium or water purifying power hydrides; Al hydrides such as sodium hydroxide, water hydrating power or lithium hydroxide. Metal hydroxides; S hydroxides; sodium metal methoxide, sodium ethoxide, potassium tert-butoxide or lithium methoxide; metal alkoxides; methylmercaptane sodium or ethyl meloxide Alkali metal mercaptans such as sodium butane; or triethylamine, tributylamine, diisopropyletylamine, N-methyl morpholine, pyridine, 4- (N, N-dimethylamino) pyridine, N, N-dimethyl aniline, N, N-getyl aniline, 1,5-diazabicyclo

 [4.3.0] Nona-5-ene, 1,4 diazabicyclo [2.2.2.2] octane (DABCO) or 1,8-diazabicyclo [5.4.0] pendeco 7-ene ( Organic amines such as DBU), more preferably gold carbonates or organic amines, more preferably organic amines (especially triethylamine). The reaction temperature varies depending on the starting compound, the reagent, the solvent and the like, but is usually from 120 to 100, preferably from 0 to 50.

 The reaction time varies depending on the starting compound, the reagent, the solvent and the reaction temperature, but is usually from 10 minutes to 12 hours, preferably from 30 minutes to 6 hours.

After completion of the reaction, the target compound of this step is collected from the reaction mixture according to a conventional method. For example, after completion of the reaction, the target compound precipitated in the reaction solution is destroyed, or the solvent is distilled off, water is added to the residue, and a water-immiscible solvent (eg, benzene, methylene chloride, ether, sulfuric acid) Then, the target compound is extracted by washing the organic layer with water, dried over anhydrous magnesium phosphate or the like, and the solvent is distilled off to obtain the target compound. The obtained target compound can be further purified, if necessary, by a conventional method, for example, recrystallization, reprecipitation », chromatography or by adding an acid to make a salt. Without disturbing the starting material There is no particular limitation as long as it dissolves. For example, aliphatic hydrocarbons such as hexane, heptane, ligroin or petroleum ether; aromatic hydrocarbons such as benzene, toluene or xylene; methylene chloride Halogenated hydrocarbon purples, such as methyl, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, or dichlorobenzene; ethers, such as getyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethyloxetane, or diethylene glycol dimethyl ether Amides such as formamide, dimethylformamide, dimethylacetamide or hexamethylphosphoric acid; or sulfoxides such as dimethylsulfoxide or sulfolane, preferably halogen. A hydrocarbon violet acids or ethers, more preferably a halogenated hydrocarbon (particularly methylene Kurori de).

 The condensing agent to be used is not particularly limited as long as it is generally used in the art of organic chemistry. For example, dicyclohexylcarbodiimide (DCC), getyl cyanophosphonate (DEPC), di ( 2-pyridyl) disulfide and triphenyl phosphine, 2-chloro-1-methylbiridinyl dimethyl or ethyl carboxylate, preferably getyl cyanophosphonate.

The base used is, for example, an alkaline metal such as sodium carbonate, potassium carbonate or lithium carbonate; an alkaline metal such as sodium carbonate aqueous purple, sodium carbonate aqueous lithium or lithium hydrogen carbonate. Bicarbonates; Alkali hydrides such as lithium-purified lithium, sodium-purified sodium or water-purified lithium hydride; Alkali hydrides such as sodium hydroxide, hydroxylated lithium or lithium hydroxide Metal hydroxides; sodium methoxide, sodium ethoxide, potassium t-butoxide or lithium methoxide; alkali metal alkoxides; methyl mercaptan tanium or ethyl mercaptan tan Alkali metal such as mercaptan; or triethylamine, tributylamine, diisopropylethylamine, N Organic amines such as methylmorpholine, pyridine, 4- (N.N-dimethylamino) pyridine, N.N-dimethylaniline or N, N-dimethylylaniline, preferably metal carbonates or organic amines And more preferably an organic (Especially triethylamine).

 The reaction temperature varies depending on the starting compound, the reagent, the solvent and the like, but is usually from 120 to 100, preferably from 0 "C to 50" C.

 The reaction time varies depending on the starting compound, reagent, solvent and reaction temperature, but is usually from 10 minutes to 24 hours, preferably from 30 minutes to 12 hours.

 After completion of the reaction, the target compound of this step is collected from the reaction mixture according to a conventional method. For example, after the completion of the reaction, the target compound precipitated in the reaction solution is removed, or the solvent is distilled off, water is added to the residue, and a water-immiscible solvent (eg, benzene, methylene chloride, ether, acetic acid) Then, the target compound is extracted by washing with water, dried over anhydrous magnesium sulfate or the like, and the solvent is distilled off to obtain the target compound. The desired target compound can be further purified, if necessary, by a conventional method, for example, recrystallization, re-sedimentation, chromatography or salting with an acid.

Method C is a method for producing compound (II).

 In the step C1, a compound having the general formula (XIV) is

 (a) reacting with a compound having the general formula (XII) in an inert solvent in the presence or absence (preferably in the presence of a base) of a base, or

 (b) by reacting with a compound having the general formula (III) in an inert solvent in the presence of a condensing agent (if necessary, in the presence of a base),

This is a step for producing a compound having the general formula (XV), and is carried out in the same manner as in Step B2.

Step C2 comprises reacting a compound having the general formula (XV) with a compound having the general formula (VIII) in the presence or absence (preferably in the presence) of a base in an inert solvent. This is a step of producing a compound having the general formula (II), and is carried out in the same manner as in Step A2. Method D is a method for producing compound (VIII), which is a raw material of Method A. In the method D, the desired compound obtained in any step can be optically resolved as desired (preferably, the optical resolution in the D1 step).

 Step D1 comprises reacting a compound having the general formula (XVI) with a compound having the general formula (XVII) in an inert solvent in the presence of a condensing agent (if necessary, in the presence of a base). Is a step of producing a compound having the general formula (XVIII), and is carried out in the same manner as in Step B2b. The compound having the general formula (XVIII) obtained by this step can be obtained by a method used in the field of ordinary organic chemistry, for example,

, Natural resolution (natural crystallization), a method using asymmetric adsorption (a method using silica gel column chromatography or high performance liquid chromatography, etc.) or a resolving reagent (for example, tartaric acid, mandelic acid or 10- Optical resolution can be carried out by a method of producing diastereomer with camphorsulfonate, etc., and preferably by silica gel column chromatography.

 Step D2 is a step of producing a compound having the general formula (XIX) by reacting the compound having the general formula (XVIII) with a reducing agent in an inert solvent.

 The solvent to be used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent. Examples thereof include aromatic hydrocarbons such as benzene, toluene and xylene; methylene chloride, and chloroform. Halogenated carbohydrate purples such as carbon tetrachloride, dichloroethane, cyclobenzene or dichlorobenzene; or ethers such as ethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxetane or diethylene glycol dimethyl ether. It is possible and preferably ethers (especially tetrahydrofuran).

The reducing agent used is not particularly limited as long as it is used in a normal reduction reaction. Examples thereof include sodium borohydride, lithium borohydride, lithium aluminum water violet, and water. Gold such as diisobutylaluminum violet or water-purified aluminum) K hydride, aluminum isopropoxide, diborane or borane-methyl sulfide, preferably borane-methyl sulfide complex You.

 The reaction temperature varies depending on the starting compound, the solvent, the reducing agent used and the like, but is usually from 20 to 100, preferably from 0 * C to 50.

 The reaction time varies depending on the starting compound, the solvent, the reducing agent used, the reaction temperature, and the like, but is usually 12 hours to 120 hours, and preferably 48 hours to 96 hours.

 After completion of the reaction, the target compound of this step is collected from the reaction mixture according to a conventional method. For example, after completion of the reaction, an acid (preferably hydrochloric acid) is added to the reaction solution, and then the target compound precipitated in the reaction solution is removed. Alternatively, an acid (preferably hydrochloric acid) is added to the reaction solution, and the reagent is added. After decomposing the reaction mixture, make the reaction solution alkaline, add a water-immiscible solvent (eg, benzene, ether, ethyl acetate, etc.) to extract the target compound, wash the extracted organic layer with water, and then use anhydrous magnesium sulfate or the like. The desired compound is obtained by drying and distilling off the solvent. If necessary, the obtained target compound can be further purified by a conventional method, for example, recrystallization, reprecipitation or chromatography.

Step D3 comprises reacting a compound having the general formula (XIX) with a compound having the formula (R 0 or R ⁸ —Y [preferably a compound having the formula (R ^e ) 0]) in an inert solvent. This is a step of producing a compound having the general formula (XX).

 The solvent used is not particularly limited as long as it does not hinder the reaction and dissolves the starting materials to some extent. For example, aromatic hydrocarbons such as benzene, toluene or xylene; methylene chloride; Halogenated hydrocarbons such as form, carbon tetrachloride, dichloroethane, cyclobenzene, or dichlorobenzene; or ethers such as ethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxetane, or diethylene glycol dimethyl ether. And preferably ethers (particularly dioxane).

 The reaction temperature varies depending on the starting compound, the reagent, the solvent and the like, but is usually from 120 to 100, preferably from 0 to 50.

The reaction time varies depending on the starting compound, reagent, solvent, reaction temperature, etc. It is 10 minutes to 12 hours, preferably 1 hour to 3 hours.

 After completion of the reaction, the target compound of this step is collected from the reaction mixture according to a conventional method. For example, after the reaction is completed, water is added to the reaction solution, if necessary, alkalinized, and then a solvent immiscible with water (for example, benzene, ether, ethyl acetate, etc.) is added to extract the target compound, and the extracted organic B Is washed with water, dried over anhydrous magnesium sulfate and the like, and the solvent is distilled off to obtain the desired compound. The obtained target compound can be further purified, if necessary, by a conventional method, for example, recrystallization, reprecipitation or chromatography.

 Step D4 is a step of reacting the compound having the general formula (XX) with a halogenoacetyl halide in an inert solvent in the presence or absence (preferably in the presence) of a base. This is a step of producing a compound having (XXI).

 The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material K to some extent. Examples thereof include aromatic hydrocarbon purples such as benzene, toluene and xylene; methylene chloride, and chloroform. Halogenated hydrocarbons such as mouth form, carbon tetrachloride purple, dichloroethane, cyclobenzene or dichlorobenzene: or ethers such as dimethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxetane or diethylene glycol dimethyl ether. And preferably ethers (particularly tetrahydrofuran).

The base used is, for example, an alkali metal carbonate such as sodium carbonate, potassium carbonate or lithium carbonate; an alkali metal bicarbonate such as sodium carbonate purple, sodium carbonate carbonate or lithium hydrogencarbonate; Alkali metal hydroxides such as sodium hydroxide, hydroxide hydroxide or lithium hydroxide; alkalis such as sodium methoxide, sodium ethoxide, potassium t-butoxide or lithium methoxide Metal alkoxides; mercaptan alkali metals such as methyl mercaptan sodium or ethyl mercaptan sodium; or triethylamine, tributylamine, diisopropylethylamine, N-methylmorpholin, Pyridine, 4- (N, N-dimethylamino) Pyridine, N, N-dimethyl Ruanirin, N, N -.. Jechiruanirin, 1, 5-Jiazabishikuro [4 3 0 ] Organics such as nona-5-ene, 1,4 diazabicyclo [2.2.2] octane (DABC0) or 1.8-diazabicyclo [5.4.0] dexco 7-ene (DBU) The halogenoacetyl halide used can be an amine, preferably an organic amine (especially pyridine). Examples of the halogenoacetyl halide used are, for example, chloroacetylheptyl chloride, bromoacetyl chloride, eodoacetyl chloride, chloroacetyl bromide. It can be mido, bromoacetyl bromide or acetyl acetyl chloride, preferably chloroacetyl chloride or bromoacetyl chloride, and particularly preferably chloroacetyl chloride.

 The reaction temperature varies depending on the starting compound, reagent, solvent and the like, but is usually from −20 to 100, preferably from 0 to 50.

 The reaction time varies depending on the starting compound, reagent, solvent, reaction temperature and the like, but is usually 5 minutes to 12 hours, preferably 10 minutes to 1 hour.

 After completion of the reaction, the target compound of this step is collected from the reaction mixture according to a conventional method. For example, after completion of the reaction, water is added to the reaction solution, a solvent immiscible with water (eg, benzene, ether, ethyl acetate, etc.) is added to extract the target compound, and the extracted organic layer is washed with water, and then dried over anhydrous magnesium sulfate. Then, the target compound is obtained by distilling off the solvent. The obtained target compound can be further purified, if necessary, by a conventional method, for example, recrystallization, reprecipitation or chromatography. The compound obtained in this step can be used in the next step without purification.

 Step D5 is a step of preparing a compound having the general formula (XXI)

 (a) After deprotection by reacting with an acid in an inert solvent, then

 (b) a step of producing a compound having the general formula (XXII) by reacting with a base in an inert solvent.

The solvent used in Step D5a is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent.Examples include aromatic hydrocarbons such as benzene, toluene and xylene. Water purple: methylene chloride, black form, carbon tetrachloride , Halogenated carbohydrate purples such as dichloroethane, cyclobenzene or dichlorobenzene; or ethers such as getyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxetane or diethylene glycol dimethyl ether. It is possible and preferably ethers, especially tetrahydrofuran.

 Acids used are, for example, mineral acids such as hydrofluoric acid, hydrochloric acid, hydrobromic acid, bromoiodic acid, acetic acid, perchloric acid, luic acid or phosphoric acid; methanesulfonic acid, trifluoic acid and the like. Sulfonic acid such as methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid or ρ—toluenesulfonic acid; or acetic acid, trifluoroacetic acid, fumaric acid, succinic acid, cunic acid, tartaric acid, oxalic acid or maleic acid It can be a carboxylic acid, preferably carboxylic acid (especially trifluoric acid).

 The reaction temperature varies depending on the starting compound, reagent, solvent and the like, but is usually -200 to 100, preferably 0 * C to 50.

 The reaction time varies depending on the starting compound, reagent, solvent, reaction temperature and the like, but is usually 5 minutes to 12 hours, preferably 10 minutes to 2 hours.

 After completion of the reaction, the target compound of this step is collected from the reaction mixture according to a conventional method. For example, after completion of the reaction, water is added to the reaction solution, a solvent immiscible with water (eg, benzene, ether, ethyl acetate, etc.) is added to extract the target compound, and the extracted organic layer is washed with water, and then dried over anhydrous magnesium sulfate. Then, the target compound is obtained by distilling off the solvent. The obtained target compound can be further purified, if necessary, by a conventional method, for example, recrystallization, reprecipitation or chromatography. The compound obtained in this step can be used in the next step without purification.

The solvent used in Step D5b is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent.Examples include hexane, heptane, ligroin and petroleum ether. Aliphatic hydrocarbons; Aromatic hydrocarbons such as benzene, toluene or xylene; Halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride purple, dichloroethane, cyclobenzene or dichlorobenzene Purples: getyl ether, diisopropyl ether, tetrahydrofuran, di Ethers such as oxane, dimethoxetane or diethylene glycol dimethyl ether: alcohols such as methanol, ethanol, propanol, isopropanol, butanol or isobutanol; formamide, dimethylformamide, dimethylacetamide or hexamethylphosphate It can be an amide such as a liamide; or a sulfoxide such as dimethyl sulfoxide or sulfolane, and is preferably an amide (particularly dimethylformamide).

 The base used is, for example, an alkaline metal such as sodium carbonate, potassium carbonate or lithium carbonate; an alkaline metal such as sodium hydrogen carbonate, a carbonated aqueous purple rim or an aqueous lithium carbonate. Bicarbonates; lithium hydride, sodium hydride or lithium hydride. Alkali hydrides: sodium hydroxide, sodium hydride, lithium hydride or lithium hydroxide. Hydroxides; alkali metal alkoxides such as sodium methoxide, sodium ethoxide, potassium tert-butoxide or lithium methoxide; such as methyl mercaptan sodium or ethyl mercaptan natrium Merkabutane alkaline metals; or triethylamine, tributylamine, diisoprovirethylamine N one-methylmorpholine, pyridine, 4-(N, N-Jimechiruamino) Pyridine, N, N-dimethyl § diphosphate, N, N-Jechiruanirin, 1. 5 Jiazabishikuro

 [4.3.0] nonane 5-ene, 1,4-diazabicyclo [2.2.2] octane (DA BCO) or 1.8-diazabicyclo [5.4.0] pendeco 7-ene ( Organic amines such as DBU), preferably alkali gold carbonates or alkali metal hydrides, more preferably alkali gold carbonates (particularly sodium carbonate or potassium carbonate). is there.

 The reaction temperature varies depending on the starting compound, the reagent, the solvent and the like, but is usually from −20 to 150, preferably from 0 to 100.

 The reaction time varies depending on the starting compound, reagent, solvent, reaction temperature and the like, but is usually 5 minutes to 12 hours, preferably 10 minutes to 2 hours.

After completion of the reaction, the target compound of this step is collected from the reaction mixture according to a conventional method. For example, after the reaction is completed, water is added to the reaction solution, and a water-immiscible solvent (eg, benzene , Ether, and ethyl diethyl acid) to extract the target compound. The extracted organic layer is washed with water, dried over anhydrous magnesium phosphate and the like, and the solvent is distilled off to obtain the target compound. If necessary, the obtained target compound can be further purified by a conventional method, for example, recrystallization, reprecipitation or chromatography.

 Step D6 is a step of producing a compound having the general formula (XXIII) by reacting the compound having the general formula (XXII) with a reducing agent in an inert solvent. Done in

 In step D7, a compound having the general formula (VIII) is produced by contacting the compound having the general formula (XXIII) with a reducing agent in an inert solvent (if necessary, in the presence of ammonium formate) It is a process.

 The solvent used is not particularly limited as long as it does not hinder the reaction and dissolves the starting materials to some extent. Examples thereof include aliphatic hydrocarbons such as hexane, heptane, rigoin or petroleum ether; Aromatic hydrocarbons such as benzene, toluene or xylene; Halogenated hydrocarbons such as methylene chloride, chloroform, purple tetrachloride, dichloroethane, chlorobenzene or dichlorobenzene: Jetyl ether, diisopro Ethers such as virether, tetrahydrofuran, dioxane, dimethoxetane or diethylene glycol dimethyl ether; alcohols such as methanol, ethanol, propanol, isopropanol, butanol or isobutanol; formamide, dimethylformamide Amides such as dimethyl acetate or hexamethyl phosphate triamide: sulfoxides such as dimethyl sulfoxide or sulfolane; fatty acids such as acetic acid; or a mixed solvent of the above organic solvent and water. Preferably, they are alcohols (particularly methanol or ethanol).

 The reducing agent used can be, for example, palladium black, palladium carbon, platinum, Raney nickel, preferably palladium charcoal purple.

 The reaction temperature varies depending on the starting compound, the solvent, the reducing agent used and the like, but is usually from 0 to 150 "C, preferably from 50 to 100" C.

Reaction time varies depending on starting compounds, solvent, reducing agent used, reaction temperature, etc. However, it is usually 10 minutes to 12 hours, preferably 30 minutes to 2 hours. After completion of the reaction, the target compound of this step is collected from the reaction mixture according to a conventional method. For example, after completion of the reaction, the catalyst is removed, and then the solvent is distilled off, or the residue obtained by distilling off the solvent is added with water, and then a water-immiscible solvent (for example, benzene, ether, (Ethyl acetate, etc.) to extract the target compound, wash the extracted organic layer with water, dry over anhydrous magnesium sulfate, etc., and evaporate the solvent to obtain the target compound. If necessary, the obtained target compound can be further purified by a conventional method, for example, recrystallization, reprecipitation or chromatography.

The hexahydrovirazinoquinoline derivative (I) or (II) or a pharmacologically acceptable salt thereof according to the present invention has excellent 5- _HT1A receptor action, sedative action against mental stress or hallucination-suppressing action. With low toxicity and side effects (especially drowsiness etc.), anxiety, B disease, hypertension, schizophrenia, sleep disorders, migraine, sexual dysfunction, motion sickness, dizziness or senile dementia peripheral symptoms It is useful as a therapeutic or preventive (particularly therapeutic) for (such as delirium).

[Best Mode for Carrying Out the Invention]

 Hereinafter, the present invention will be described more specifically with reference to Examples, Reference Examples, Test Examples, and Formulation Examples, but the scope of the present invention is not limited thereto.

 In the description of the NMR spectrum, the abbreviation nd indicates that the cleavage pattern is unknown due to overlap with a solvent or another signal.

 Example 1

 3- (4-phthalimidobutyl) -1,2,3,4,4a.5,6-hexahydro-1H-birazino [1,2, a] quinoline dihydrochloride

 (Exemplary compound number: 2-46)

 (a) 3— (4-phthalimidobutyl) 1-2,3,4.4a, 5,6—hexahi draw 1H—Virazino [1,2—a〗 quinoline

2,3,4,4a.5,6-hexahydrol 1H-birazino [1,2-a) quinoline (4.54 g) and N- (4-promobutyl) phthalimid (6 . 8 1 Was dissolved in dimethylformamide (50 ml), and then potassium carbonate (3.7 g) was added, followed by stirring at 100 for 30 minutes. After the reaction solution was cooled, it was poured into water and extracted with ethyl acetate. After the extract was washed with water, it was dried using anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and a small amount of ether was added to the obtained oil to crystallize. Hexane was added and the mixture was collected to give the desired compound (7.5 1 g, 80%).

 ¾ point: 82-86;

 NMR spectrum (CDC la) δ ppm: 1.5-2.0 (6H, m). 1.92 (1 1, t, J = 11 1), 2.21 (1 2., dt, J = 1 1 Η,, J = 3 Η ζ), 2.42 (2 Η, t, J = 7 Η ζ), 2.6-2.75 (1 Η, m), 2.75 -2.95 (3Η, m), 2.95-3.1 (2Η, m), 3.65-3.8 (1Η, η d). 3.73 (2Η, m) t. J = 7 Η), 6.69 (1, t, J = 7 Η), 6.78 (1, d, J = 8 Η), 6.97 (1, d, J = 7 Η)), 7.08 (1 Η, t, J = 7 Η ζ), 7.7-7.8 (2 H, m), 7.8-7.9 (2 H, m) ,

 (b) 3— (4-phthalimidobutyl) -1,2,3,4,4a, 5,6-hexahi draw 1H—Virazino [1,2—a] quinoline dihydrochloride

 3- (4-phthalimidobutyl) 1-2,3.4,4a, 5,6-hexahydro-1H-virazino [1,2-a] quinoline (120 mg) is added to ethanol ( After dissolving in 10 ml), an excess of 10 N hydrochloric acid / methanol solution was added, and the mixture was allowed to stand at room temperature for 30 minutes. After evaporating the solvent under reduced pressure, the obtained residue was recrystallized from ethanol to quantitatively obtain the target compound as colorless needles.

 Melting point: 220-224.

 Example 2

 3- (4-benzamide-butyl) -1-2.3.4, 4a, 5, 6-hexahydro-1H-birazino [1,2-a] quinolin monohydrochloride

 (Exemplary compound number: 1-25)

(a) 3— (4-benzamide butyl) 1 2.3.4, 4a, 5.6—hexahi draw 1H—birazino [1,2-a] quinoline 3- (4-Aminobutyl) 1,2,3,4,4a, 5.6-Hexahidraw 1H—Virazino [1,2—a] quinoline (240 mg) in tetrahydrofuran ( The mixture was dissolved in 15 ml), and triethylamine (165 w1) and benzoyl chloride (1251) were added dropwise while stirring at room temperature. After stirring at room temperature for 1 hour, the precipitated crystals were removed by 1 and the solvent was distilled off under reduced pressure. The obtained residue was purified using silica gel column chromatography (eluent: ethyl acetate: methanol = 20: 1) to obtain the desired compound (284 mg. 76%).

 Melting point: 1 3 5— 1 3 7;

NMR Subeku torr _{(CDC 1 3) 5 ppm:} .... 1 5 5 - 1 8 (5 H, m), 1 8- 1, 8 6 (1 Η, m), 1 8 9 (1 Η, t , J = 1 1Η ζ), 2.17 (1, dt, J = 1 2 Η, J = 3 Η), 2.42 (2 Η, t, J = 7 Η), 2.69 (1,, ddd, J = 16 Η, J = 5 Η, J = 4 Η), 2.75-2.92 (3 Η, m). -3.02 (2 Η, m), 3.50 (2 Η, q, J = 6 Η ζ, change to 3.49 (2 Η, t, J = 6 Η に よ り) by adding D0 ), 3.74 (1 Η, dt, J = 12, J = 3 Η), 6.55-6.75 (1 Η, br.s, disappeared by adding D0), 6. 6 9 (1Η, t, J = 7Hz), 6.78 (1H.d, J = 8Hz). 6.98 (1H, d, J = 7Hz), 7. 0 8 (1H, t, J = 7Hz), 7.38-7.5 (3H, m), 7.74 (2H, d, J = 7Hz);

IR spectrum (（Β Γ) ν, ·, cm- ¹ : 3277, 1641.

 (b) 3 — (4-benzamide butyl) 1,2,3,4,4a, 5,6—hexahi draw 1 H—Virazino [1,2—a] quinoline monohydrochloride

 3— (4-benzamide butyl) obtained in Example 2a—1,2,3,4.4a, 5,6-hexahi draw 1 H—virazino [1,2—a] quinoline (2 82 mg) was dissolved in ethyl acetate (15 ml), and a 4 N hydrogen chloride / ethyl acetate solution (1901) was added dropwise. After stirring at room temperature for 1 hour, the precipitated crystals were collected to obtain the desired compound (232 mg, 75%).

Melting point: 193-200 (decomposition): NM R spectrum Bok Honoré _{(DMS O - d e) δ} ppm:... 1. 5 - 1 7 (3 H, m), 1 7- 1. 85 (2 H, m), 1 9 - 2 0 (1 H, m), 2.66 (1 H, dt, J = 16 Hz, J = 5 H z). 2.75-2.9 (2 H, m), 3. 0-3.2 (4H, m), 3.25-3.45 (3H, nd), 3.5-3.65 (2H, m), 4.08 (1H, d, 6.69 (1 H, t, J = 7 Hz), 6.90 (1 H, d, J = 8 Hz), 6.98 (1 H, d, J = 7.06 (1 H, t, J = 7 H z), 7.47 (2 H, t, J = 7 H z), 7.53 (1 H, t, J = 7 H z), 7.86 (2 H, d, J = 7 H z), 8.56 (1 H, t, J = 6 H z), 10. 35-1 0.5 .5 5 (1 H, br • s);

IR spectrum (KBr) v ... cm " ¹ : 3261, 2552, 2515, 2474, 1649.

 Example 3

 3- (4-benzamidebutyl) 1-2,3,4,4a, 5,6-hexahydro-1H-birazino [1,2-a] quinoline dihydrochloride

 (Exemplary compound number: 1-25)

3- (4-phthalimidobutyl) 1-2,3,4,4a, 5,6-hexahydrol obtained in Example 1a 1H-Virazino [1.2-a] quinoline (53 1 mg ) Was dissolved in ethanol (10 ml), hydrazine hydrate (166 M1) was added, and the mixture was heated under reflux for 6 hours. After cooling to room temperature, the mixture was passed through M, the solvent was distilled off under reduced pressure, and the obtained residue was dried under vacuum. The residue was dissolved in tetrahydrofuran (10 ml), and triethylamine (760 μl) and benzoyl chloride (158 / X1) were added thereto under ice-cooling, followed by stirring at room temperature for 2 hours. . After water was added to the reaction solution, the solvent was distilled off under reduced pressure, and the obtained residue was added to a saturated aqueous sodium hydrogen carbonate solution. After extracting the product with methylene chloride, the organic JB was washed with saturated aqueous sodium hydrogen carbonate solution and dried using anhydrous magnesium phosphate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (eluent: 4% ethanol / methylene chloride solution), and an excess of 10% hydrochloric acid / methanol solution was added. Release for 30 minutes Was placed. The solvent was distilled off under reduced pressure, and the obtained residue was recrystallized from ethanol to give the target compound (471 mg. 79%) as colorless needles.

 Contact point: 1 99-1 203

 NMR spectrum (DMSO-ds) δ ppm: 1.5-2.1 (6H, m), 2.7-2.9 (3H, m), 3.0-3.2 (4 H.m), 3.2-3.4 (3H, nd), 3.5-3.6 (2H, m), 4.0--4.2 (1H, m), 6.6 J (7.3Hz), 6.90 (1H, d, J = 7.9Hz), 6.97 (1H, d, J = 7.3Hz) ), 7.06 (1 H, dd, J = 7-3 H z. J = 7.9 H z), 7.4-7.6 (3 H, m), 7.86 (2 H, d, J = 6.6 Hz), 8.55 (1H.t, J = 5.3 Hz).

 Example 4

 3-ί4-(2-Fluorobenzamide) butyl] 1,2,3,4.4a, 5,6-hexahidraw 1H-Virazino [1,2, a] quinoline monohydrochloride

 (Exemplary compound number: 1-33)

 3- (4-Aminobutyl) 1-2,3,4,4a, 5,6-Hexahi draw: LH-Virazino [1,2-a] quinoline (332 mg) and 2-Fluorochloride The target compound (255 mg, 70 mg) was obtained by reacting benzoyl (154 w 1) in the same manner as in Examples 2a and 2b and performing post-treatment.

 Melting point: 1805-2000 (decomposition);

 NMR spectra (DMSO—ds) δ ppm: 1.5-1.7 (3H, m), 1.7-1.9 (2H, m), 1.9-2. 0 (1 H, m), 2.67 (

Dt, J = 16 Hz, J = 5 Hz), 2.75-2.9 (2 H, m), 3.0-3.2 (4 H. M), 3. 2-3.45 (3H, nd), 3.45-3.

6 5 (2H, m) .4.07 (1H, d, J = 12Hz), 6.69 (1H, t.J = 7Hz). 6.90 (1H , d, J = 8 Hz), 6.97 (1 H, d, J = 7 Hz). 7.06 (1 H, t. J = 8 Hz), 7.25-7.35 (2 H. M), 7.45-7.55 (1 H, m), 7.62 (1 H, dt, J = 8 H z, J = 2 H z). 1 H. T .J = 5 H z), 10.0.75-1 1 .05 ( 1 H, br. S):

IR spectra (KBr) "-,, cm— ¹ : 3307, 2557, 2515, 2473, 1672.

 Example 5

 3- [4- (3-Fluorobenzamide) butyl] 1,2,3,4,4a, 5,6-hexahydro 1H-Virazino [1.2-a] quinoline monohydrochloride salt

 (Exemplary compound number: 1-39)

 3- (4-Aminobutyl) 1,2,3,4,4a, 5,6-Hexahi draw 1H-birazino [1,2—a] quinoline (263 mg) and 3-fluochloride Benzoyl (123 / X1) was reacted in the same manner as in Examples 2a and 2b, and worked up to give the desired compound (210 mg, 49%).

 Melting point: 190-201 (decomposition);

NM R scan base click Honoré _{(DMS 0- d 6) δ ppm} :... 1. 5 - 1. 7 (3 H, m), 1 7- 1 85 (2 H, m) 1. 9- 2. 0 (1H, m), 2.66 (1H, dt, J = 16Hz, J = 5Hz), 2.75-2.9 (2H, m), 3.0-3 2 (4 H, m), 3 2-3.5 (3 H, nd), 3.55 (2 H, t, J = 1 2 H z), 4.08 (1 H, d, J = 1 1 Hz), 6 · 69 (1 H. T, J = 7 Hz), 6.90 (1 H, d, J = 8 Hz), 6.98 (1 H, d, J = 7 Hz), 7.06 (1H, t, J = 8Hz), 7.38 (1H, dt, J = 9Hz, J = 2Hz), 7.53 (1H, dt, J = 8 Hz, J = 6 Hz), 7.67 (1 H, dd, J = 8 Hz, J = 2 Hz), 7.73 (1 H, d, J = 8 Hz), 8.68 (1H, t, J = 6Hz), 100.5-10.9 (1H, br. S);

 I R Spectrum (KBr) v cm-, ： 3 28.6.256 1, 2 5 1 4 .2 47 3, 1 6 5 6.

 Example 6

3- [4- (4-fluorobenzamide) butyl] 1-2,3.4,4a, 5.6-hexahydro 1H-Virazino [1,2-a] quinoline dihydrochloride salt (Example compound number: 1-44)

 3- (4-Aminobutyl) 1-2,3,4,4a, 5,6-Hexahydro 1H-birazino [1,2—a) quinoline (200 mg) in tetrahydrofuran 10 ml), add triethylamine (118 w1) and 4-fluorobenzoyl chloride (102 w1) under ice-cooling and stirring, and add 2 hours at room temperature. Agitated. After water was added to the reaction solution, the solvent was distilled off under reduced pressure, and the obtained residue was added to a saturated aqueous sodium hydrogen carbonate solution. After the product was extracted with methylene chloride, the organic layer was washed with a saturated aqueous solution of sodium hydrogen carbonate and dried using anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: 4% ethanol / methylene chloride solution), and an excess of 1 ON hydrochloric acid / methanol / ethanol solution was added. Let stand for minutes. The solvent was distilled off under reduced pressure, and the obtained residue was recrystallized from ethanol to give the desired compound (228 mg, 65%) as colorless needles.

 ft point: 2 34 (decomposition).

 Example 7

 3— [4- (2,3-Difluoro mouth benzene amide) butyl] 1,2,3,4,4a, 5.6-Hexahi draw 1H—Virazino [1,2—a] quinoline monohydrochloride Salt (Exemplary Compound No .: 1-150)

 3- (4-Aminobutyl) 1,2,3,4,4a, 5,6-Hexahidraw 1H-birazino [1.2-a] quinoline (177 mg) and 2,3-chloride Difluo benzoyl (90 w1) was reacted in the same manner as in Examples 2a and 2b and worked up to give the desired compound (172 mg, 6096).

 Melting point: 172-174;

NM R scan base click preparative Honoré _{(DM SO- d e) 5 ppm} :. 1. 5 - 1. 7 (3 H, m), 1 7 - 1. 85 (. 2 H m), 1. 9 one 2 0 (1 H, m), 2.67 (1 H, dt, J = 16 Hz, J = 5 H z). 2.75-2.9 (2 H. M), 3.0 — 3.2 (4 H, m), 3.25-3.4 (3 H, nd), 3.5 — 3.6 (2 H, m). 4.09 (1 H, d, J = 8 H z). 6.70 (1 H, t. J J = 8 Hz), 6.98 (1 H, d, J = 7 Hz). 7.06 (1 H, t, J = 8 Hz), 7.25-7.35 (1H, m), 7.41 (1H, dd, J = 8Hz, J = 6Hz), 7.5-7. 6 (1H, m), 8.56 (1H, t, J = 5Hz), 10.4-10.7 (1H, br. S);

IR spectrum (KBr)-"cm— ¹ : 32262.2584, 2569, 2489, 1664,

 Example 8

 3-[4- (2,4-difluorobenzamide) butyl] 1,2,3,4,4a, 5,6-hexahidraw 1H-Virazino [1,2, a] quinoline Monohydrochloride (Exemplary compound number: 1-155)

 3- (4-aminobutyl) 1-2,3,4,4a, 5,6-hexahydro 1H-birazino [1,2-a] quinolin (332 mg) and 2,4-difluochloride Oral benzoyl (160 μl) was reacted in the same manner as in Examples 2a and 2b, followed by post-treatment to obtain the target compound (191 mg, 44%).

 Melting point: 190-197 (decomposition);

NMR spectrum Honoré _{(DM SO- d 6) δ ppm} :. 1. 5 - 1. 7 (3 H, m), 1. 7 - 1 8 5 (. 2 H m), 1. 9 - 2. 05 (1 H, m) .2.67 (1 H, dt, J = 16 Hz, J = 5 Hz), 2.75-2.9 (2 H, m), 3.0 — 3. 2 (4 H, m), 3.29 (2 H, dd, J = 13 H z, J = 7 H z), 3.3 — 3.4 (1 H, nd). 3 54 (2 H, t, J = 13 Hz), 4.08 (1 H, d, J = 11 Hz), 6.69 (1 H, t, J = 7 Hz), 6.90 (1H, d, J = 8Hz), 6.98 (1H, d, J = 7Hz), 7.06 (1H, t, J = 8Hz), 7. 1 8 (1 H, dt, J = 9 H z, J = 3 H z), 7.36 (1 H, ddd, J = 11 H z, J = 9 H z. J = 2 H z), 7.70 (1 H. Dt, J = 8 Hz, J = 7 Hz), 8.40 (1 H, t, J = 5 Hz). 10 .6-10 .9 (1 H. br. S);

IR spectrum (KBr) v ... cm: 32 3 7.25 69, 25 36 , 25 17. 2 47 7.

 Example 9

 3-[4-(2, 5-difluorobenzamide) butyl]-1, 2, 3.4, 4a, 5.6-hexahi draw 1 H-virazino [1, 2-a] quinoline Hydrochloride (Exemplary compound number: 1-163)

 3 — (4-Aminobutyl) 1,2,3,4,4a, 5,6-Hexahi draw 1H-Virazino [1,2—a] quinoline (177 mg) and 2,5 chloride —Difluo benzoyl (90ii 1) was reacted in the same manner as in Examples 2a and 2b and worked up to give the desired compound (176 mg, 72%).

 »Point 1 6 8 — 1 7 2;

NMR spectrum (DMS 0-d ₆ ) S p 'pm: 1.5-1.7 (3H.m), 1.7-1.85 (2H, m), 1.9-2. 0 5 (1Η, m), 2.67 (1Η, dt.J = 16 6, J = 5Η), 2.75-2.9 (2Η, m), 3. 0-3.2 (4Η, m), 3.25-3.45 (3Η, ηd), 3.54 (2Η, t, J = 13 3), 4.0 8 (1Η, d, J = 11 1), 6.69 (1Η, t.J = 7Η), 6.90 (1Η, d, J = 8Η), 6 9 8 (1 Η. D, J = 7 Η), 7.06 (1 Η, t, J = 8 Η), 7.3-7.5 (3 Η, m), 8.5 0 (1Η, t, J = 5Η), 10.6.5-10.95 (1Η, br.s);

IR spectra (KBr) V cm " ¹ : 3237, 2562, 2539, 2510, 2479, 1662.

 Example 10

 3 — [4- (2,6-difluorobenzamide) butyl] -1 2.3,4,4a, 5.6-hexahi draw 1H—Virazino [1.2—a] quinoline Monohydrochloride (Exemplary compound number: 1-68)

3-((4-aminobutyl) 1-2,3,4,4a.5.6-hexahidraw 1H-birazino [1.2-a] quinoline (171 mg) and 2.6 chloride -Reaction and post-treatment of difluo benzoyl (910) in the same manner as in Examples 2a and 2b As a result, the target compound (146.4 mg, yield 55%) was obtained.

 Melting point: 1944-1200 X: (decomposition):

NMR spectrum Honoré _{(DMSO- d 6) δ ppm:} ..... 1 5 - 1 7 (3 H, m), 1 7 - 1 8 5 (2 H, m), 1 9 one 2.0 (1H, m), 2.67 (1H, dt, J = 16Hz, J = 5Hz), 2.81 (2H, ddd, J = 16Hz, J = 1 1 Hz, J = 5 Hz), 3.0--3.2 (4 H, m), 3.2-3.4 (3 H, nd), 3.5-3.6 (2 H , m), 4.09 (1H, d. J = 8Hz), 6.69 (1H, t, J = 7Hz), 6.90 (1H, d, J = 6.97 (1 H, d, J = 7 H z), 7.06 (1 H, t, J = 8 H z), 7.18 (2 H, t, J = 8 Hz), 7.52 (1H, tt, J = 8Hz, J = 7Hz), 8.79 (1H, t, J = 6Hz), 10.4 -10.6 (1 H, br. S);

IR spectrum (KBr) vcm " ¹ : 3204, 2566, 2538, 2503, 2469, 1659.

 Example 1 1

 3- [4- (3,4-difluorobenzamide) butyl] 1,2,3,4,4a, 5.6_hexahi draw 1H-Virazino [1,2—a] quinoline Monohydrochloride (Exemplary Compound No .: 1-173)

 3- (4-Aminobutyl) 1-2,3,4,4a, 5,6-Hexahydro-1H-birazino [1,2, a] quinoline (177 mg) and chloride 3. 4-Difluorobenzoyl (90 91) was reacted in the same manner as in Examples 2a and 2b and worked up to obtain the desired compound (92.6 mg, yield 33%). .

 Melting point: 168-174 (decomposition);

NMR spectrum (DMSO-ds) δ ppm: 1.55-1.7 (3H, m), 1.7—1.85 (2H, m), 1.9-2. 0 (1H, m), 2.66 (1H, dt.J = 16Hz, J = 5Hz), 2.75-2.9 (2H, m) .3.0 -3.2 (4H.m), 3.2-3.45 (3H, nd), 3.5-3 • 65 (2H, m) .4.0-4.15 ( 1 H, m), 6.69 (1 H, t, J J = 8 Hz), 6.90 (1 H, d, J = 7 Hz), 7.06 (1 H, t, J 7.56 (1 H, dt, J = 10 Hz, J = 8 Hz), 7.7-7.8 (1 H, m), 7.92 (1 H, ddd,

J = 1 2 H z, J = 8 H z, J = 2 H z), 8 68 H,, J = 5 H z), 10 .1 5-10 .5 5 (1 H, b r. s);

IR spectrum (KBr) cm "': 328.12.583, 2518

 Example 1 2

 3— [4— (3,5-difluorobenzamide) butyl] 1,2,3,4,4a, 5,6-hexahi draw 1H—Virazino [1,2—a] quinoline Monohydrochloride (Exemplary compound number: 1-179)

3- (4-aminobutyl) 1,2,3,4,4a, 5,6-hexahydro 1H-birazino [1,2—a] quinoline (177 mg) and 3,5-chloride Jifuruo port base Nzoiru (90 mu 1) are reacted analogously to example 2 a and 2 b, and by post, _beta to give the desired compound (1 46 mg, yield 5 1%)

 »Point: 1 74-1 77 ^ (decomposition);

NM R-spectrum Honoré _{(DM SO- d 6) 6 ppm} :. 1. 55 - 1. 7 (3 H, m), 1 7 - 1. 85 (2 H, m), 1. 9 one 2 2.66 (1 H, dt, J = 16 Hz, J = 5 Hz), 27.5-2.9 (2 H, m), 2. 9 5-3.25 (4 H, m). 3.25-3.45 (3 H. Nd), 3.5-3.65 (2 H, m), 4.0-4 15 (1H, m), 6.69 (1H, t, J = 7Hz) .6.90 (1H, d.J = 8Hz), 6.97 (1H, d, J = 7Hz), 7.06 (1H, t, J = 8Hz), 7.4-17.5 (1H, m), 7.58 (2H, dd. = 8 Hz, J = 2 Hz), 8.76 (1 H, t, J = 5 Hz). 10. 25-10 .55 (1 H, b r. S);

IR spectrum (KBr) v ... cm- ¹ : 32 85.2600, 25580.25 14.2.501, 1656.

Example 13 3- [4-1 (3,4-dichlorobenzamide) butyl] -1,2,3,4,4a, 5,6-hexahidraw 1H-Virazino [1,2, a] quinoline Hydrochloride (Exemplary compound number: 1-9 2)

 3- (4-Aminobutyl) 1-2,3,4,4a.5,6-Hexahi draw 1H-birazino [1,2-a] quinoline (230 mg) and 3,4-chloride Benzoyl dichloride (215 mg) was reacted in the same manner as in Examples 2a and 2b, and worked up to give the desired compound (174 mg, 36%).

 Melting point: 192-201 (decomposition);

NM R scan base click Honoré _{(DM SO- d e) δ ppm} :... 1 5 - 1 7 (3 H, m), 1. 7- 1 85 (2 H, m), 1. 9 one 2. 0 (1 H, m), 2.66

(1 H, dt, J = 16 Hz, J = 5 Hz), 2.75-2.9 (2 H, m), 3.0-3.2 (4 H, m), 3. 2-3.5 (3 H, nd), 3.5-3.6

(2H, m), 4.09 (1H, d, J = 10Hz), 6.70 (1H.t.J = 7Hz), 6.90 (1H, d. 6.98 (1H, d, J = 7Hz), 7.06 (1H, t, J = 8Hz), 7.77 (1H.d, J = 9 Hz), 7.85 (1 H, dd, J = 9 Hz, J = 2 Hz), 8.10 (1 H, d, J = 2 Hz), 8.76 (1 H, t, J = 5 H z). 10. 2-10. 45 (1 H, br. S);

IR spectrum (KBr) v ... cm " ¹ : 32 64, 2 580, 2477, 1653, 1642.

 Example 14

 3-[[4- (4-methylbenzamide) butyl] 1-2,3,4,4a, 5.6-hexahydro 1H-virazino [1,2-a] quinoline dihydrochloride

 (Exemplary compound number1 1 1 1 1)

3- (4-aminobutyl) -1-2.3,4,4a, 5,6-hexahydro 1H-birazino [1,2-a] quinoline (200 mg), 4-toluoyl chloride ( 112 μl) and triethylamine (118 il) were reacted in the same manner as in Example 6 and post-treated to obtain the target compound (199 mg, 57%). Melting point: 208-211.

 Example 15

 3- [4- (3-trifluoromethylbenzamide) butyl] 1,2,3,4,4a, 5,6-hexahi draw 1H-Virazino [1,2—a] quinoli —Hydrochloride (Exemplary Compound No .: 1-111)

 3- (4-aminobutyl) 1-2,3,4,4a, 5.6-hexahydro 1H-Virazino [1,2-a] quinoline (240 mg) and 3-tritrifluoromethylbenzoyl chloride (160 μl) was reacted in the same manner as in Examples 2a and 2b, and post-treated to obtain the desired compound (296 mg, 65%).

 Melting point: 185-18;

NM R spectrum _{(DMS O- d 6) δ ppm} :.. 1 5 5 - 1. 7 (3 H, m), 1 · 7 - 1 9 (2 H, m), 1. 9 one 2.0 (1 H, m), 2.66 (1 H, dt, J = 16 H z, J = 5 H z), 2.75-2.9 (2 H, m), 3.0-3 2 (4 H, m), 3.25-3.4 (3 H, nd), 3.5-3.6 (2 H, m), 4.08 (1 H, d, J = 9 Hz), 6.69 (1H, t, J = 7Hz), 6.90 (1H, d, J = 8Hz), 6.97 (1H, d.J = 7Hz) ), 7.06 (1 H, t, J = 8 Hz). 7.73 (1 H, t, J = 8 Hz), 7.92 (1 H. D, J = 8 Hz) ), 8.19 (1H, d, J = 8Hz), 8.20 (1H, s), 8.85 (1H, t, J = 5Hz), 10.4 -10.6 (1 H, br. S);

 I R Sk. レ (レ "Γ) ,," "ΠΙ- ': 3305. 2438. 1 664 Example 16

 3-[4- (4-trifluoromethylbenzamido) butyl] 1, 2,3,4,

4 a, 5,6-Hexahi draw 1 H-Virazino [1,2-a] quinolin-hydrochloride (Exemplary Compound No .: 1-124)

3- (4-aminobutyl) 1,2,3,4,4a, 5,6-hexahi draw 1H-biradino [1,2-a] quinoline (266 mg) and 4-trifluoromethine chloride Rubenzoyl (160 u1) was reacted in the same manner as in Examples 2a and 2b and worked up to give the desired compound (131 mg, 42%).

 »Point: 1 98—204” C (decomposition);

NM R scan base click Honoré _{(DMS O- d 6) δ ppm} :. 1. 5 5 - 1. 7 (3 H, m), 1 7 - 1. 85 (2 H, m), 1. 9 one 2 0 (1 H, m), 2.66 (1 H, dt, J = 16 H z. J = 5 H z), 2.75-2.9 (2 H, m), 3. 0—3.2 (4 H, m), 3.25-3.4 (3 H, nd), 3.45-3.6 (2 H, m), 4.08 (1 H, d , J = 9 Hz), 6.69 (1 H, t, J = 7 Hz), 6.90 (1 H, d, J = 8 Hz), 6.97 (1 H. D, J = 7 Hz), 7.06 (1 H, t, J = 8 Hz). 7.86 (2 H, d, J = 8 Hz), 8.06 (2 H, d, J = 8 Hz), 8.8 1 (1 H, t, J = 5 Hz), 10.4-10 .55 (1 H, b r. S);

IR spectacle (KB r) v «.cm” ¹ : 3297, 2596, 2486 Example 17

 3- [4- (2-methoxybenzamide) butyl] 1,2,3,4,4a, 5,6-hexahi draw 1H-Virazino [1,2—a] quinoline monohydrochloride

 (Example compound number: 1-1 3 1)

 3- (4-aminobutyl) 1,2,3,4,4a, 5,6-hexahydrol 1H-birazino [1,2-a] quinoline (250 mg) and 2-methoxybenzoyl chloride (145 μl) was reacted in the same manner as in Examples 2a and 2b and worked up to give the desired compound (191 mg, 57%).

 Melting point 1668-170;

NMR spectrum (DMS 0— _ds ) δ ppm: 1.5-1.7 (3H, m), 1.7-1.85 (2H, m) .1.9-1 2.0 (1 H, m), 2.67 (1 H. Dt, J = 16 Hz, J = 5 Hz), 2.75-2.9 (2 H, m), 3.0-3 3.2-3.45 (3 H, nd), 3.5-3.65 (2 H, m), 3.89 (3 H. S), 4. 0 9 (1 H. D, J = 10 Hz ), 6.70 (1H, t.J = 7Hz) .6.90 (1H, d.J = 8Hz), 6.98 (1H, d, J = 7Hz) ), 7.03 (1H, t, J = 7Hz) .7.06 (1H, t, J = 7Hz), 7.14 (1H, d, J = 9Hz) ), 7.46

(1 H, dt, J = 8 Hz, J = 2 Hz), 7.7 1 (1 H. Dd, J = 8 Hz, J = 2 Hz), 8.23 (1 H, t, J = 6 H z), 1 0.25-1 0.45

(1H, br.s);

 IR spectrum (KBr) v «" cm— ': 3360, 2457, 1642 Example 18

 3- [4- (4-Methoxybenzamide) butyl] 1,2,3,4,4a, 5.6-Hexahi draw 1H-Virazino [1,2, a] quinoline dihydrochloride

 (Exemplary compound number: 1-13 9)

 3- (4-aminobutyl) 1-2,3,4,4a, 5,6-hexahydr 1H-birazino [1.2-a] quinoline (200 mg), 4-anisyl chloride (14 5 mg) and triethylamine (118 M1) were reacted in the same manner as in Example 6 and worked up to give the desired compound (236 mg, 6696).

 Melting point: 2 15—2 19

 Example 19

 3— [4- (4-Phenylbenzamido) butyl] —2,3,4,4a, 5.6-Hexahi draw 1H—Virazino [1,2—a] quinoline dihydrochloride

 (Exemplary compound number: 1-147)

 3- (4-Aminobutyl) 1,2,3,4,4a, 5,6-HexahiDraw 1H-Viradino [1,2—a] Quinoline (200 mg), 4-Bif chloride Enylcarbonyl (184 mg) and triethylamine (1181) were reacted in the same manner as in Example 6 and worked up to give the desired compound (69 mg, 17%).

 »Points: 1 94- 1 98.

 Example 20

3-[4- (4-cyanobenzamide) butyl] 1-, 2, 3, 4, 4a, 5, 6 1-hexahydro draw 1H-birazino [1.2-a] quinoline monohydrochloride

 (Exemplary compound number: 1-1 6 5)

 3- (4-aminobutyl) 1-2,3,4.4a.5,6-hexahydro 1H-birazino [1.2-a] quinoline (332 mg) and 4-cyanobenzoyl chloride (2 24m) was reacted in the same manner as in Examples 2a and 2b and worked up to give the desired compound (2 15 mg. 44%).

 Melting point 206-218-C (decomposition);

NMR Subeku torr _{(DM SO - d s) δ} ppm:.. 1. 55 - 1. 7 (3 H, m), 1 7- 1 85 (2 H, m), 1. 9 one 2.0 (1 H, m), 2.66 (1 H, dt, J = 16 Hz, J = 5 Hz), 2.7-2.9 (2 H, m), 3.0—3.2 (4H, m), 3.25-3.4 (3H, nd), 3.55 (2H, t, J = 12Hz), 4.07 (1H, d, J = 1 1Hz), 6.69 (1H, t, J = 7Hz), 6.90 (1H, d, J = 8Hz), 6.98 (1H, d, J = 7H) z), 7.06 (1 H, t. J = 8 Hz), 7.97 (2 H, d, J = 8 Hz), 8.03 (2 H, d, J = 8 Hz) , 8-86 (1H, t, J = 5Hz), 10 .65-10.85 (1H, br. S);

IR spectrum (KB r vx., Cm ' ¹ : 3216, 2578, 2558, 2538.2521, 2478.22, 29, 1649.

 Example 2 1

 3— [4- (412-trobenzamide) butyl] 1-2,3,4,4a, 5,6-hexahi draw 1H—Virazino [1,2—a] quinoline dihydrochloride

 (Exemplary compound number: 1-174)

 3- (4-aminobutyl) 1-2,3,4,4a, 5.6-hexahydr 1H-birazino [1,2-a] quinoline (200 mg), 412-trobenzoyl chloride (157 mg) and triethylamine (118 M1) were reacted in the same manner as in Example 6 and worked up to obtain the desired compound (235 mg, 63%).

 Melting point: 2 13-2 16

Example 22 3- (2-benzamidoethyl) -1-2.3,4.4a, 5,6-hexahydro-1H-birazino [1,2-a] quinoline monohydrochloride

 (Exemplary compound number: 1-23)

 3- (2-aminoethyl) -1,2,3,4,4a, 5,6-hexahydrol 1H-birazino [1,2-a] quinoline (280 mg) and benzoyl chloride (145 μl ) Was reacted in the same manner as in Examples 2a and 2b, followed by post-treatment to obtain the desired compound (158 mg, 41%).

 »Point: 1 7 9-1 841C (disassembly):

NM R spectrum Bok Honoré _{(DM SO- d 6) δ ppm} : 1. 55 - 1. 7 (1 H, m), 1. 85 - 2. 0 (1 H, m), 2. 6 - 2 7 (1H.m), 2.75-3.0 (2H.m), 3.0-3.2 (2H, m), 3.2-3.5 (4H, nd ), 3.6-3.85 (3H, m), 4.05-4.2 (1H, m), 6.69 (1H, t, J = 7Hz), 6. 9 1 (1H, d, J = 7Hz), 6.97 (1H, d, J = 7Hz), 7.06 (1H, t, J = 8Hz), 7. 49 (2H, t, J = 7Hz), 15.6 (1H, t, J = 7Hz), 7.93 (2H.d, J = 7Hz), 8.8 -9.0 (1H, br.s), 100.5-10.9 (1H, br.s);

IR spectrum (Κ Β Γ) «« ·· cm- ¹ : 3300, 2 582.25 2 0 1, 1 65 3 _β

 Example 23

 3-[2-(2.4-difluorobenzamide) ethyl] 1, 2, 3, 4, 4a.5, 6-hexahi draw 1H-virazino [1.2-a] quinoline Hydrochloride (Exemplary compound number: 1-53)

 3- (2-aminoethyl) -1-2.3,4,4a, 5.6-hexahydro-1H-biradino [1.2-a] quinoline (222 mg) and chloride 2.4 -Difluo benzoyl (130At1) was reacted in the same manner as in Examples 2a and 2b, and worked up to give the desired compound (173 mg, 46%).

»Point: 1 7 5— 1 82" C (decomposed); NMR spectrum _{(DMSO - d B) 5 ppm} :.... 1 6 - 1 7 (1 H, m), 1, 9 one 2 0 (1 H, m) , 2 6 7 (1 H, dt. J = 16 Hz, J

2.8 1 (1 H, ddd. J = 16 Hz, J = 11 Hz, J = 5 Hz), 2.8 5-3.0 (1 H. M ), 3.0-3.2 (2 H, m), 3.2-

3.6 (3 H, n d), 3.6-3.8 (4 H, m), 4.1 1 (1 H, d, J

= 13 Hz), 6.70 (1 H, t, J = 7 Hz), 6.92 (1 H, d, J =

6-98 (1H, d, J = 7Hz), 7.06 (1H.t, J = 8Hz), 7.22 (1H, dt, J = 8 Hz, J = 2 Hz), 7.40 (1 H, ddd, J = 11 Hz, J = 9 Hz, J = 2 Hz), 7.8 1 (1 H, q, J = 8

H z), 8.67 (1 H, b r. S), 10.5-10.7 (1 H, b r. S)

IR spectrum (KB iv-., Cm ' ¹ : 3378, 2558, 2464, 1659.

 Example 2 4

 3 — (3—Benzamidoprovir)-2.3,4,4a, 5,6—Hexahydro 1 H—Virazino [1,2—a] quinoline monohydrochloride

 (Exemplary compound number: 1-124)

 3— (3-aminobutyral pill) 1,2,3,4,4a, 5,6-hexahi draw 1 H-Virazino [1,2—a] quinoline (209 mg) and benzoyl chloride (1 10 p. 1) was reacted in the same manner as in Examples 2a and 2b and worked up to give the desired compound (128 mg, 37%).

 Sun point: 1 8 3-1 8 9 * 0 (decomposition);

NMR spectrum (DMS 0-d ₆ ) δ ppm: 1.55-1.7 (1H, m), 1.9-2.1 (3H, m), 2.66 (1H. dt, J = 16 Hz. J = 5 Hz), 2.7-2.95 (2 H, m). 3.0-3.25 (4 H, m), 3.25 -3.5 (3H, nd), 3.58 (2H, t.J = 12Hz), 4.08 (1H, d, J = 9Hz), 6.69 (1H, t, J = 7Hz), 6.90 (1H.d, J = 8Hz), 6.97 (1H.d, J = 7Hz), 7.0 6 ( 7.48 (2H, t, J = 8Hz), 7.54 (1H, t, J = 7Hz). 7.88 (1H, t, J = 8Hz). 2 H, d, J = 7 Hz), 8.70 (1 H, t, J = 6 Hz). 10. 55-1 0.75 (1 H. Br. S);

IR spectrum Honoré (KB r) ν · ,, c m '1: 3 3 0 5, 2 5 5 3, 2 4 7 3, 1 6 4 5.

 Example 2 5

 3- (4-Ivaloylaminobutyl) 1-2,3.4,4a.5,6-Hexahidraw 1H-Virazino [1,2-a] quinoline monohydrochloride

 (Exemplary compound number: 1-6)

 3- (4-Aminobutyl) 1,2,3,4,4a, 5,6-Hexahi draw 1H monobirazino [1,2—a] quinoline (250 mg) and bivaloyl chloride (1 64 μl) was reacted in the same manner as in Examples 2a and 2b, and post-treated to obtain the desired compound (125 mg, 35%).

 »Point: 1 9 3-2 0 * C (decomposition):

... NMR spectrum _{(DMS 0- d e) δ ppm} :.. 1 1 0 (. 9 H s), 1 4- 1 5 (2 H, m), 1 5 5 - 1 7 5 (3 H m), 1.9-2.0 (1H, m), 2.67 (1H.dt, J = 16Hz, J = 5Hz), 2.75-2.9 (2 H, m). 3.0-3.2 (6 H, m), 3.3-3.4 (1 H, nd), 3.45-3.6 (2 H, m), 4.08 (1 H, d, J = 10 H z). 6.69 (1 H, t, J = 7 H z), 6.90 (1 H, d, J = 8 H z) ), 6.98 (1 H, d. J = 7 H z). 7.06 (1 H. T, J = 7 H z), 7.53 (1 H, t. J = 5 H z), 10.4-10. 6 (1 H, br. s);

IR spectrum (KBr) ν »·, cm: 33 06, 25 59, 25 24, 24 75, 16 48.

 Example 26

3 — [4- (2-Ethylhexanoylamino) butyl] 1,2,3,4,4a .5.6-Hexahi draw 1H-Virazino [1,2, a] quinoline monohydrochloride (example) Compound number: 1 — 1 1) 3- (4-aminobutyl) 1-2,3,4,4a.5,6-hexahydro-1H-birazino [1,2-a] quinoline (190 mg) and 2-ethyl chloride Hexanoyl (2001) was reacted in the same manner as in Examples 2a and 2b and worked up to give the desired compound (74.8 mg, 48%).

 Melting point: 1 1 5—1 2 1;

. NM R spectrum _{(DM SO- d 6) δ ppm} : 0. 7 9 (3 H, t, J = 7 H z), 0. 84 (3 H, t, J = 7 H z) 1 1 - 1.5 (10H, m), 1.55-1.8 (3H, m), 1.9-205 (2H, m), 2.67 (1H, dt, J = 16 Hz, J = 5Hz), 275-2.9 (2H, m), 3.0-3.2 (6H, m), 3.25-3.45 (1 3.45-3.6 (2H, m), 4.08 (1H, d, J = 10Hz), 6.69 (1H, t, J = 7Hz) ) 6.90 (1 H, d, J = 8 Hz), 6.98 (1 H, d, J = 7 Hz), 7.06 (1 H, t, J = 8 Hz), 7.89 (1 H, t, J = 6 Hz), 10.5-10.7 (1 H, b r. S);

 IR spectrum (KBr) v „" cm: 3284, 2581, 2473, 164 9ο

 Example 2 7

 3- (4-cyclohexylcarbonylaminobutyl) 1,2,3,4,4a, 5,6-hexahydrol 1H-virazino [1,2—a] quinoline monohydrochloride

 (Exemplary compound number: 1-120)

 3- (4-Aminobutyl) — 2,3.4,4a, 5,6-Hexahidraw 1H-birazino [1,2-a] quinoline (230 mg) and cyclohexylcarbonyl chloride (140 M 1) was reacted in the same manner as in Examples 2a and 2b and worked up to give the desired compound (131 mg. 43%).

 »Point: 190-196 (decomposition);

NMR Spectrum (DM SO—d _e ) 5 ppm: 1.1-1.5 (7H, m). 1.55-1.8 (8H.m), 1.9 2.0 (1 Η, m), 2.07 (1 J, tt. J = 11 Η ζ. J = 3 Η), 2.67 (1 Η, dt, J = 16) H z, J = 5 H z), 2.75-2.9 (2 H, m). 2.95-3.2 (6 H, m), 3.25-3.45 ( 1H, nd), 3.45-3.6 (2H.m) .4.08 (1H.d, J = 10Hz), 6.69 (1H, t, J = 7 Hz), 6.90 (1H, d, J = 8Hz), 6.98 (1H, d, J = 7Hz), 7.0

6 (1H, t, J = 8Hz), 7.75 (1H, t, J = 5Hz), 10.4-10.6 (1H, br. S);

IR spectrum (KBr) v „,, cm- ¹ : 32 68, 2 565, 2 480, 24 9.

 Example 2 8

 3- [4- (3-cyclohexylureido) butyl] 1,2,3,4.4a, 5,6-hexahi draw 1H-Virazino [1,2-a] quinoline

 (Exemplary compound number: 1-18 1)

 3- (4-Aminobutyl) 1-2,3,4,4a, 5,6-Hexahydro-1H-birazino [1,2-a] quinoline (213 mg) is converted to THF (10 ml) And cyclohexyl isocyanate (110 M 1) was added dropwise under stirring at room temperature. After standing overnight, the reaction solution was poured into water and extracted with ethyl acetate. The extract was washed with water and dried over anhydrous sodium triluate, and the solvent was distilled off under reduced pressure. The resulting residue was purified using silica gel column chromatography (eluent; ethyl acetate: methanol = 10: 1) to obtain the desired compound (190 mg, 60%).

 Melting point: 1 3 3— 1 37;

NM R spectrum _{(CDC 1 3) δ ppm:} ... 1. 05 - 1 2 (3 H, m), 1. 2 5 - 1 4 (2 Η, m), 1 5 - 1. 65 (3 65, m), 1.65 — 1.8 (6 Η, m), 1.85-2.0 (3 Η, m), 2.12 (1 Η, t, J = 1 1 Η) , 2.40 (1 Η, dt. J = 1 1 Η, J = 2 Η).

7 (2Η, t, J = 8Η), 2.71 (1Η, dt, J = 16 6. J = 5Η), 2.89 (1Η, ddd. J = 16 Hz, J = 11 Hz, J = 5 Hz), 3.0-3.15 (2 H. M), 3.15-3.3 (3 H, m). 3 4 5-3-6 (1 H, m). 3.82 (1 H. d. J = 12 H z). 4.29 (1 H. d) , J = 8 Η ζ), 4.75-5.05 (1 Η, br. S), 6.72 (1 Η. T, J = 7 Η), 6.79 (1 Η, d , J = 8 Η ζ), 6.99 (1,, d. J = 7 Η ζ), 7.09 (1 Η, t, J = 8 ζ ζ);

IR spectrum (Κ Β Γ) ν „·, cm— ¹ : 3 3 3 1 1 630

 Example 2 9

 3— [4- (3-phenylureido) butyl] 1-, 2,3,4,4a, 5,6-Hexahydro-1H-birazino [1,2-a] quinoline

 (Exemplary compound number: 1-1 86)

 3- (4-Aminobutyl) 1,2,3,4,4a, 5,6-Hexahydro 1H-birazino [1,2-a] quinoline (242 mg) and phenyl isocyanate (1 20 M 1) was reacted in the same manner as in Example 28, and worked up to give the desired compound (230 mg, 65%).

 Melting point: 1 55-1 57:

NM R spectrum _{(DM SO- d e) δ ppm} :.. 1. 4 - 1 7 (5 H, m), 1 7 6 (1 H, t, J = 1 1 H z), 1. 8 - 1.9 (1H, m), 2.04 (1H, dt, J = 11Hz, J = 3Hz), 2.31 (2H, t, J = 6Hz), 2.4-2.8 (3H, m), 2.8-3.0 (3H, m), 3.09 (2H, q.J = 6Hz), 3.75 (1 H, d, J = 13 Hz), 6.14 (1 H, t, J = 6 Hz), 6.60 (1 H, t, J = 7 Hz), 6.79 ( 1 H, d, J = 8 Hz), 6.86 (1 H. D, J = 7 Hz), 6.91 (1 H, d, J = 6 Hz), 6.99 (1 H, d, J = 8 Hz) .7.20 (2H, t, J = 8Hz), 7.37 (2H, d, J = 8Hz), 8.38 (1H br. s

)

IR spectrum (KBr) v ... cm " ¹ 33 05. 1 642

 Example 30

3- (4- [3- (2.4-difluorophenyl) perido] butyl] -1-2.3.4,4a, 5,6-hexahi draw 1H-birazino [1.2-a〗 quino Lin (Exemplary compound number: 1-2008) 3- (4-aminobutyl) -1-2.3,4,4a, 5,6-hexahydro 1H-birazino [1,2-a] quinoline (242 mg) and 2,4-isocyanic acid Difluorophenyl (130 μl) was reacted in the same manner as in Example 28, and worked up to give the desired compound (360 mg, 93%).

 »Point: 106-109;

NM R spectrum _{(CDC 1 3) δ ppm:} 1. 55 - 2. 0 (6 H, m to 1. 93 (1 H, t, J = 1 1 Η ζ), 2 - 2 0 (1 Η, dt, J = 1 2 Η ζ. J = 3 H z), 2.35-2.5 (2 Η, m), 2.65-2.8 (1 Η, m), 2.8-3 -1 (5Η, m), 3.25-3.4 (2Η, m), 3.78 (1Η, d, J = 1 22ζ), 5.1 — 5.9 ( 1, br. S), 6.27 (1, br. S), 6.70 (1 H, t. J = 7 H z), 6.75-6.9 (3 H, m), 6.98 (1H, d, J = 7Hz), 7.09 (1H, t, J = 8Hz), 7.98 (1H, dt, J = 10Hz) , J = 6 Hz);

IR spectrum (Κ Β Γ) ν- ·, cm- ¹ : 3332, 1686.

 Example 3 1

 3- [4- (3-tenolamino) butyl] 1,2,3,4,4a, 5,6-hexahi draw 1H-Virazino [1,2—a] quinoline monohydrochloride

 (Exemplary compound number: 1-345)

 (a) 3- [4- (3-tenolamino) butyl] 1,2,3,4,4a, 5,6-hexahi draw 1H-Virazino [1,2—a] quinoline

3- (4-Aminobutyl) -1-2.3,4.4a, 5,6-Hexahi draw 1H-Virazino [1,2-a] quinoline (238 mg), 3-tenoylic acid (1 Into a mixture of 18 mg) and dichloromethane (5 ml), triethylamine (230 µl) and getyl cyanophosphonate (DEPC, 240 µl) were added dropwise at room temperature with stirring. After being left overnight at room temperature, the reaction solution was poured into ice water and extracted with ethyl acetate. The organic calendar was washed with water, dried over anhydrous sodium rutherate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent: ethyl acetate) to obtain the desired compound (275 mg, 81%). NM R spectrum _{(CDC 1 3) δ ppm:} . 1. 6- 1 9 (. 6 H m), 1. 94 (1 H, t, J = 1 1 H z), 2. 2 2 (1 H , dt, J = 1 1 Hz, J = 3 Hz), 2.46 (2 H, t, J = 7 Hz), 2.6-2.75 (1 H, m), 2.8 -2.95 (3H, m), 2.95-3.1 (2H, m). 3.47 (2H, q, J = 6Hz), 3.76 (1H, dt) , J = 12 Hz, J = 2 Hz), 6.35-6.55 (1 H, b r.s), 6.70 (1 H, t, J = 7 Hz) , 6.79 (1 H, d, J = 8 Hz). 6-98 (1 H, d, J = 7 Hz), 7.09 (1 H, t, J = 8 Hz), 7.3 1 (1 H, dd, J = 5 Hz, J = 3 Hz), 7-38 (1 H, d, J = 5 Hz), 7.84 (1 H, d, J = 3 H z);

IR spectrum _{(CHC 1 3) vc m- '} : 345 6, 1 652.

 (b) 3- [4- (3-tenolamino) butyl] 1,2,3,4,4a, 5,6-hexahi draw 1H-Virazino [1,2, a] quinoline monohydrochloride

 3-[4-(3-Tenylamino) butyl] 1,2,3,4.4 a, 5,6-hexahi draw 1 H-Virazino [1,2, a] quinoline (257 mg) Then, the reaction was carried out in the same manner as in Example 2b, and post-treatment was carried out to obtain the desired compound (19 Omg, 67%).

 Melting point 1 98-203 (decomposition);

NMR spectrum _{(DMS O - d e) δ} ppm:.. 1. 5- 1. 7 (3 H, m), 1 7- 1 85 (2 H, m), 1. 9 one 2.0 (1 H, m), 2.66

(1 H, dt, J = 16 Hz, J = 5 Hz), 2.75-2.9 (2 H, m), 3.0-3.2 (4 H. M), 3 2 7 (2 H, dd, J = 13 Hz, J = 7 H z), 3.3-3.45 (1 H, nd), 4.08 (1 H, d. J = 9 H z), 6.69 (1 H, t. J = 7 H z), 6.90 (1 H, d, J = 8 H z), 6.97 (1 H. d, J = 7 H z) , 7.06 (1 H. T, J = 8 H z), 7.5 1

(1 H, dd, J = 5 Hz, J = 1 Hz), 7.58 (1 H, dd, J = 5 Hz, J = 3 Hz). , J = 3 Hz, J = 1 Hz), 8.4 1

(1 H. T. J = 6 H z), 10. 45-10. 65 (1 H, b r. S): IR spectrum (KBr) v- ,, cm— ': 3274, 2579, 2540

 Example 3 2

 3- [4- (1-Methylindole-2-carbonylamino) butyl] 1,2,3,4,4a, 5,6-Hexahidraw 1H-Virazino [1,2-a] quinoline Monohydrochloride (Exemplary compound number: 1-1233)

 3-, (4-aminobutyl) -1-2.3,4,4a.5,6-hexahydro 1H-birazino [1.2-a] quinoline (171 mg) and 1-methylin Dole-2 monobasic rubonic acid (120 mg) was reacted in the same manner as in Examples 31a and 31b and worked up to give the desired compound (184 mg, 65%).

 Melting point: 1997-2081: (decomposition);

NMR spectra (DMS 0—d ₆ ) δ ppm: 1.55-1.7 (3H, m), 1.7—1.85 (2H, m), 1.92 0 (1 H, m). 2.66 (1 H, dt, J = 16 H z, J = 5 H z), 2.75-2.9 (2 H, m), 3. 0-3.25 (4 H, m), 3.25-3.45 (3 H, nd), 3.5-3.65 (2 H, m), 3.99 (3 H , s), 4.09 (1H, d, J = 9Hz), 6.69 (1H, t, J = 7Hz), 6.90 (1H, d, J = 8Hz) ), 6.97 (1H, d, J = 7Hz), 7.0-7.15 (3H, nd) .7.27 (1H, t, J = 8Hz), 7.53 (1H, d, J = 8Hz), 7.63 (1H, d, J = 8Hz), 8.58 (1H, t, J = 6Hz), 1 0.4-10.5.5 (1H, br.s);

IR spectrum (Κ Βινν ·, cm- ¹ : 3 300, 242 5, 2 405, 2 359, 1653.

 Example 3 3

 3 .— (4,1-nicotinylaminobutyl) -1-2.3,4,4a.5.6-Hexahydr 1H-Virazino [1,2-a] quinoline monohydrochloride

 (Exemplary compound number: 1-24 1)

3— (4-aminobutyl) 1 2. 3, 4.4 a, 5.6—Hexahi draw 1 H By reacting monobirazino [1,2—a] quinoline (266 mg) and nicotinyl chloride hydrochloride (192 mg) in the same manner as in Examples 2a and 2b, The compound (184 mg, 63%) was obtained.

 Rasp point: 2 0 7-2 1 0 (decomposition);

NMR-spectrum Honoré _{(DMSO- d 6) S ppm:} ..... 1 5 5 - 1 7 (3 H, m), 1 7 - 1 8 5 (2 H, m), 1 9 one 2 0 (1 Η, m), 2.66 (1 Η, dt, J = 16 Η, J = 5 Η). 2.75-2.9 (2,, m), 3. 0—3.25 (4Η, m), 3.25-3.45 (3Η, ηd), 3.45—3.6 (2Η, m), 4.80 ( 1Η, d, J = 8Η 8), 6.69 (1Η, t. J = 7Η), 6.90 (1Η, d, J = 8Η), 6.97 (1 Η, d, J = 7 Η ζ), 7.06 (1 Η, t, J = 8 Η ζ), 7.5 1 (1 Η, dd, J = 8 Η,, J = 5 Η ζ), 8.21 (1Η, dt, J = 8Η, J = 2Η), 8.71 (1Η, dd, J = 5Η, J = 2Η), 8 9 8 (1,, t, J = 5 Η). 9.03 (1 Η, d, J = 2 Hz), 10.5-10.7 (1 Η, br. S) ;

IR spectrum (Κ Β Γ) ν, ·, cm— ¹ : 3 2 5 5, 2 5 6 1, 2 5 1 4, 2 4 7 6, 1 6 5 2.

 Example 3 4

 3-, [4- (2-Virazinecarbonylamino) butyl] -1-2.3,4,4a.5,6—Hexahidraw 1H-Virazino [1,2—a] quinoline monohydrochloride

 (Exemplary compound number: 1-2 4 8)

 5- (4-Aminobutyl) 1-2,3,4.4a.5,6-hexahidraw 1H-birazino [1.2-a] quinoline (171 mg) and virazine-1— Potassium rubonic acid (86 mg) was reacted in the same manner as in Examples 31a and 31b and worked up to give the desired compound (96.5 mg, 42%).

 »Point 1 6 8-1 7 41C;

NMR-spectrum Honoré _{(DMS 0- d 6) 5 ppm} :...... 1 5 5 - 1 7 (3 H, m), 1 7 - 1 8 5 (2 H, m) 1 9 - 2.0 (1H.m), 2.6 6 (1 H, dt, J = 16 H z, J = 4 H z), 2.75-2.9 (2 H, m)

, 3.0-3.2 (4H.m). 3.25-3.45 (3H, nd), 3.45-3.65 (2H, m), 4.0 7 (1 H, d, J = 9 Hz), 6.69 (1 H, t, J = 7 Hz). 6.90 (1 H, d, J = 8 Hz), 6- 9 7 (1 H. D, J = 7 Hz), 7.06 (1 H, t, J = 8 Hz), 8.74 (1 H, d, J = 2 Hz), 8 8 8 (1 H, d, J = 2 H z), 9.04 (1 H, t, J = 6 H z). 9. 20 (1 H, d, J = 1 H z), 10.4-10.7 (1H, br • s);

IR stake (IR Β Γ Γ) ν «· ο πι- ¹ : 3 2 7 6, 2 5 8 6, 2 5 6 2

 Example 3 5

 3- [4- (4-quinolinecarbonylamino) butyl] 1-2,3.4,4a, 5,6-hexahidraw 1H-Virazino [1,2—a] quinoline monohydrochloride Salt (Exemplary compound number: 1 — 2 5 7)

 3- (4-aminobutyl) -1,2,3,4,4a, 5,6-hexahydro 1H-birazino [1.2-a] quinoline (171 mg) and quinoline 4-Carboxylic acid (122 mg) was reacted in the same manner as in Examples 31a and 31b, and worked up to give the desired compound (122 mg, 48%).

 »Points: 159-16-164;

NMR spectrum _{(DMS 0- d 6) δ ppm} :...... 1 5 5 - 1 7 (3 H, m) 1 8- 1 9 (2 H, m), 1 9 - 2. 0 ( 1 H. M), 2.67

(1 H .dt, J = 16 Hz, J = 6 Hz), 2.75-2.9 (2 H, m), 3.0-3.25 (4 H.m), 3.25-3.45 (1H.nd), 3.40

(2 H, dd, J = 13 H z, J = 7 H z) .3.57 (2 H, t, J = 13 H z), 4.09 (1 H, d. J = 6.70 (1H, t.J = 7Hz), 6.91 (1H.d, J = 8Hz) .6.98 (1H, d, J = 7 H z),

7.06 (1H, t, J = 8Hz), 7.58 (1H, d, J = 4Hz), 7.68 (1H, t.J = 8Hz) , 7.82 (1 H, t, J = 8 Hz), 8.09 (1H.d, J = 8Hz), 8.15 (1H.d, J = 8Hz) .8.85 (1H, t, J = 6Hz). 1 H, d. J = 4 Hz), 10.55- 10.7.75 (1H, br. S);

 IR Spectra (KBr) v cm — ': 32236, 2585. 2499, 2474, 1656.

 Example 3 6

 3- [4- (2-furoilamino) butyl] 1,2,3,4,4a, 5.6-hexahi draw 1H-Virazino [1,2-a] quinoline monohydrochloride

 (Exemplary compound number: 1-2 62)

 3- (4-aminobutyl) 1-2,3,4,4a, 5,6-hexahydro 1H-birazino [1,2-a] quinolin (250 mg) and 2-fluoroinole ( The target compound (131 mg., 40%) was obtained by reacting 1051) in the same manner as in Examples 2a and 2b and performing post-treatment.

 K point 184-190: (decomposition);

 NMR Spectra (DMSO—ds) δ ppm: 1.5-1.85 (5H, m), 1.9-2.0 (1H, m), 2.66 (1H, m) dt, J = 16 Hz. J = 5 Hz), 2.75-2.9 (2 H. m), 3.0-3.2 (4 H, m), 3.26 ( 2H, dd, J = 13Hz, J = 7Hz) .3.3-3.4 (1H, nd), 3.45-3.6 (2H, m), 4. 08 (1 H, d, J = 9 H z), 6.62 (1 H, dd, J = 3 H z, J = 2 H z), 6.69 (1 H, t, J = 7 H z), 6.90 (1H, d, J = 8Hz), 6.97 (1H, d.J = 7Hz), 7.06 (1H, t, J = 8H) z), 709 (1 H, d. J = 3 H z), 7.83 (1 H, s), 8.44 (1 H, t J = 6 H z), 10.3-10 6 (1 H. br. S);

IR spectrum (KBr) v ... cm— ¹ : 3249.22.585, 2542, 2482.16.62ο

 Example 37

3— [2— (2-Tenylamino) ethyl]-To 2.3, 4, 4a, 5.6- Kisahi Draw 1H-Virazino [1,2-a] quinoline monohydrochloride (Exemplary Compound No .: 1-283)

 3- (2-aminoethyl) 1-2,3,4,4a.5,6-hexahi draw 1H-birazino [1,2-a] quinoline (222 mg) and 2-thenoyl chloride (115 Ml) was reacted in the same manner as in Examples 2a and 2b and worked up to give the desired compound (231 mg, 71%).

 »Point: 186—198 (decomposition);

 NMR spectra (DMS 0-de) 6 ppm: 1.55-1.7 (1H.m), 1.9-2.0 (1H, m), 2.67 (1H , dt, J = 16 Hz, J = 5 Hz), 2.81 (1 H, ddd, J = 16 Hz, J = 11 Hz, J = 5 Hz), 2. 9 1 (1 H, q, J = 1 1 H z), 3.05-3.2 (2 H, m). 3.25-3.6 (3 H, nd), 3.6-3 8 (4 H, m), 4.10 (1 H, d, J = 10 Hz), 6.70 (1 H, t, J = 7 Hz), 6.91 (1 H , d, J = 8 Hz), 6.98 (1 H. d, J = 7 Hz), 7.06 (1 H, t, J = 8 Hz), 7.17 (1 H, t, J = 4 Hz), 7.79 (1 H, d, J = 4 Hz), 7.91 (1 H, d, J = 3 Hz), 9.00 (1 H, br. s). 10. 7-10 .95 (l H. br. s);

IR spectrum (KBr) ν- ·, cm " ¹ : 3270, 2590.2472.1642.

 Example 38

 3 -— [2- (3-—Tenylamino) ethyl] —2,3,4,4a.5.6—Hexahi Draw 1H—Virazino [1,2—a] quinoline monohydrochloride

 (Exemplary compound number: 1-343)

3- (2-aminoethyl) -1,2,3,4,4a, 5,6-hexahydrol 1 H-birazino [1,2-a] quinoline (222 mg), 3-tenoyl acid ( 124 mg) and getyl cyanophosphonate (240 / zl) were reacted in the same manner as in Examples 31a and 31b, followed by post-treatment to obtain the desired compound (223 mg, 65%). Melting point: 187-195 (decomposition);

NMR spectrum (DMS 0—d ₆ ) δ ppm: 1.58-1.7 (1 H.m). 1.9-2.0 (1 H.m), 2.67 (1 H, dt, J = 16 Hz, J = 5 Hz), 2.8 1 (1 H, ddd. J = 16 Hz, J = 11 Hz, J = 5 Hz), 2.9 1 (1 H, q, J = 1 1 H z), 3.05-3.2 (2 H, m), 3.2-3.6 (3 H, nd), 3.6-3. 8 (4 H, m), 4.10 (1 H, d, J = 9 Hz), 6.70 (1 H, t, J = 7 Hz), 6.91 (1 H, d, J = 8Hz), 6.98 (1H, d, J = 7Hz), 7.06 (1H, t.J = 8Hz), 7-58 (1H, dd, J = 5 Hz, J = 1 Hz), 7.6 1 (1 H, dd, J = 5 Hz. J = 3 Hz). 8.26 (1 H, d, J = 2 H z), 8.82 (1 H, br. s), 100.7-11.0 (1 H. br. s);

IR spectra (Κ Β Γ) Ι / ·, cm— ¹ : 3290, 2651, 2591, 2476, 1650.

 Example 3 9

 3-[2- (3-Methylthiophene-2-carbonylamino) ethyl] -2.3,4,4a, 5,6-HexahiDraw 1H-Virazino [1,2, a] quinoline Monohydrochloride (Exemplary compound number: 1 — 302)

 3- (2-Aminoethyl) 1-2,3,4,4a, 5,6-Hexahydr-1-H-birazino [1,2-a] quinolin (222 mg), 3-methyl Thiophene-l-ruvonic acid (137 mg) and getyl cyanophosphonate (240 / xl) were reacted in the same manner as in Examples 31a and 31b, followed by post-treatment to obtain the desired compound (242 mg, 70%).

 »Points 1 74-1 86 (decomposition);

NM R spectrum _{(DM S 0- d B) δ} pp ra:... 1. 58 - 1 7 (1 H, m) 1 9 - 2. 0 (1 H, m), 2. 45 (3 H , s), 2.67 (1 H, dt. J = 16 Hz. J = 5 Hz), 2.8 1 (1 H, ddd, J = 16 Hz. J = 11 Hz J = 5 Hz), 2.92 (1 H. Q, J = 11 Hz). 3.05-3.2 (2 H. M), 3.2-3.6 (3 H . nd). 3. 6—3.8 (4 4.11 (1H, d, J = 1 1Hz), 6.70 (1H, t, J = 7

6.92 (1 H, d, J = 8 Hz) 6.97 9 (1 H. D, J = 8 Hz), 6.98 3 (1 H, d, J = 5 Hz) 7.06 (1H, t, J = 8Hz), 7.6 1 (1H, d.J = 5Hz), 828 (1H, t, J = 5Hz), 100.6-10.8 (lH.br.s);

 IR spectrum (KBr) v „,, cm_ '3 300, 25 5 2.25 26, 2464, 1641 1

 Example 40

 3- [2- (5-Methylthiophene-2-carbonylamino) ethyl] 1,2,3.4,4a, 5,6-hexahidraw 1H-Virazino [1,2—a] quinoline —Hydrochloride (Exemplary compound number: 1 — 307)

 3- (2-aminoethyl) -1,2,3,4,4a, 5,6-hexa-dani draw 1H-birazino [1,2—a] quinoline (222 mg), 5-methylthiophene 1 2 1-Rubonic acid (137 mg) and getyl cyanophosphonate (240 / xl) were reacted in the same manner as in Examples 31a and 31b, and the target compound (1 85 mg. 60%).

 »Point: 201-210 * C (decomposition);

NMR spectrum _{(DMS 0- d e) δ ppm} :... 1 5 5 - 1 7 (1 H, m), 1 9 one 2. 0 (1 H, m) , 2. 4 7 (3 H. s), 2.67 (1H, dt, J = 16Hz, J = 5Hz), 2.81 (1H, ddd, J = 16Hz, J = 11Hz) J = 5 Hz), 2.85-3.0 (1 H, m), 3.0-3.2 (2 H, m), 3.2-3.6 (3 H, nd) , 3.6-3.8 (4H.m), 4.10 (1H, d, J = 11Hz), 6.70 (1H, t, J = 7Hz). 6.87 (1H, d, J = 4Hz), 6.91 (1H, d, J = 8Hz), 6.98 (1H, d, J = 7Hz) , 7.06 (1 H, t, J = 8 Hz), 7.69

(1 H, d. J = 4 H z). 8.85 (1 H, b r. S), 10 .6-1 0.9. 9

(1H, br.s):

IR spectrum (KBr) v ... cm— ': 3269, 2710 0.2663 06

, 2590, 2501, 2465, 1644.

 Example 4 1

 3- [4- (2-Tenylamino) butyl] 1-2,3,4,4a, 5,6-hexahi draw 1H-Virazino [1,2, a] quinoline monohydrochloride

 (Exemplary compound number: 1-2 85)

 3- (4-Aminobutyl) 1-2,3,4,4a, 5,6-Hexahidraw 1H-birazino [1.2-a] quinoline (330 mg) and 2-tenol chloride (1 40 μl) was reacted in the same manner as in Examples 2a and 2b, and post-processed to obtain the desired compound (341 mg, 65%).

 »Point: 1 9 8—2 1 4 (decomposition);

NMR spectrum (DMS 0— _ds ) δ ppm: 1.5-1.7 (3H, m), 1.7-1.85 (2H, m), 1.9-2.0 (1 H, m), 2.66 (1 H, dt, J = 16 Hz, J = 4 H z), 2.75-2.9 (2 H, ra), 3

0-3.2 (4 H, m) 3.28 (2 H. Dd, J = 13 H z. J = 7 H z), 3.3-3.4 (3 H nd), 4. 0—4.15 (1 H, m), 6.69

(1 H, t, J = 7 Η ζ) 6.89 (1 H, d, J = 8 H z), 6.97 (1

,, d, J = 7 ζ ζ), 706 (1H, t, J = 8Hz), 7.15 (1H, t, J = 4Hz) 7.74 (1H, d , J = 4 Hz), 7.79 (1 H, d, J = 4 Hz), 859 (1 H, t, J = 5 Hz), 10.4-1 0.7 ( 1 H, br. S);

IR spectrum (V »·, cm ^-1 ) 3249, 2583, 2542, 2486.

 Example 4 2

 3- [4- (5-chlorothiophene-2-cyclocarbonylamino) butyl] -1-2.3,4,4a.5.6-hexahidraw 1H-birazino [1.2-a] quinolin —Hydrochloride (Exemplary compound number: 1 — 2 99)

3- (4-aminobutyl) -1-2.3,4,4a, 5.6-hexahydro 1H-birazino [1,2-a] quinolin (213 mg) and 5-chlorothio Fen-ichi 2 The desired compound (127 mg, 35%) was obtained by reacting with rutile acid (135 mg) in the same manner as in Examples 31a and 31b and performing post-treatment.

 1 »point: 1 96—205 (decomposition);

NMR spectrum Honoré _{(DMS 0 - d e) δ} ppm: 1. 5 - 1. 85 (5 H, m), 1. 9 one 2. 0 (1 H, m) , 2. 66 (1 H. dt, J = 16 Hz, J = 4 Hz), 2.80 (1 H, ddd, J = 16 Hz, J = 11 Hz. J = 6 Hz), 3.0- 3.2 (4H, m), 3.2-3.4 (3H, nd), 3.45-5.6.5 (2H, m) .4.08 (1H, d, J 6.69 (1 H, t, J = 7 Hz), 6.90 (1 H, d, J = 8 Hz), 6.97 (1 H. D, J = 7 Hz), 7.06 (1H.t, J = 8Hz), 7.19 (1H, d, J = 4Hz), 7.69 (1H, d, J = 4H) J), 8.72 (1 H. t. J = 5 H z). 10. 25-10. 65 (1 H, br. s);

IR spectrum (KBr) Vcm- ¹ : 319, 2671, 2591, 1641.

 Example 43

 3- [4- (3-Methylthiophene-2-carbonylamino) butyl] 1,2,3,4,4a, 5,6-hexahidraw 1H-Virazino [1,2-a] quinoline Monohydrochloride (Exemplary compound number: 1 — 304)

 3- (4-Aminobutyl) -1,2,3,4,4a, 5,6-HexahiDraw 1H-Virazino [1,2-a] quinoline (228 mg) and 3-methylthiophene (2) Rubutyric acid (125 mg) was reacted in the same manner as in Examples 31a and 31b and worked up to give the desired compound (198 mg, 56%).

 »Points: 1 78-1 at 82:

NMR spectrum (DMS 0- _ds ) δ ppm: 1.5—1.7 (3H, m), 1.7—1.85 (2H, m), 1.9—2.0 ( 1 H, m), 2.41 (3 H. S), 2.66 (1 H, dt, J = 16 H z, J = 5 H z), 2.80 (2 H, dd d J = 1 1 Hz, J = 6 Hz), 3.0-3.2 (4 H. M), 3.25 (2 H. Dd, J = 1 3 H z, J = 7 H z), 3.25 -3.45 (1H.nd), 3.45-3.65 (2H, m) .4.08 (1H, d.J = 9Hz) .6.99 (1H.t, J = 7 Hz), 6.90 (1 H. D, J = 8 Hz), 6.96 (1 H, d, J = 7 Hz), 6.97 (1 H, d. J = 8 Hz), 7.06 (1H, t, J = 8Hz), 7.56 (1H, d, J = 5Hz), 8.00 (1H, t, J = 6) Hz), 10.4—10.65 (1H.br.s);

 IR vector (KBr) v ", cm- ': 3349, 3259, 2526.2473.162.9.

 Example 44

 3- [4- (5-Methylthiophene-2-carbonylamino) butyl] 1,2,3,4,4a, 5,6-hexahidraw 1H-Virazino [1,2—a] quinoline —Hydrochloride (Exemplary compound number: 1 — 309)

 3- (4-Aminobutyl) 1,2,3,4,4a, 5,6-Hexahi draw 1H-Birazino [1,2, a] quinoline (2 13 mg) and 5-methylthiophene 2 Reactive rubonic acid (117 mg) was reacted in the same manner as in Examples 31a and 31b and worked up to give the desired compound (189 mg, 60%).

 Melting point: 2 08—2 1 7 (decomposition):

 NM R Dust (DM SO—ds) 6 PP m: 1.5-1.85 (5H, m), 1.9-2.0 (1 1, m), 2.45 (3Η , S), 2.66 (1 Η, dt, J = 16 Η, J = 5 Η), 2.75-2.9 (2 Η, m). 4 Η, m), 3.25 (2 =. Dd, J = 13 Η ζ. J = 7 Η), 3.25-3.4 (1 Η, nd), 3.5-3 65 (2 Η, m), 4.0-4.15 (1 Η, m), 6.69 (1 Η, t, J = 7 Η), 6.83 (1 Η. D, J = 4 Η), 6.90 (1, d, J = 8 Η). 6.97 (1, d, J = 7 Η). 7.06 (1 H, t. J = 8 Η ζ). 7.55 (1,, d. J = 4 Hz), 8.4-8.5 (1 Η, br. S), 10.3-1 0.55 (1 H, br. S):

IR spectrum (KBr) v ... cm— ¹ : 32 54, 25 58.247 0 .1 6 3 0.

 Example 4 5

 3— [4- (4-Methoxythiophene-1-3-carbonylamino) butyl] 1,2,3,4,4a, 5,6-Hexahydro-1H-birazino [1.2-a) quinolin Monohydrochloride (Exemplary Compound No.

 3- (4-Aminobutyl) -1-2.3,4,4a, 5,6-Hexahi draw 1H-birazino [1,2-a〗 quinoline (2 l 3 mg) and 4-methoxythiophene 3-Capillonic acid (130 mg) was reacted in the same manner as in Examples 31a and 31b, followed by post-treatment to obtain the desired compound (198 mg, 57%).

 Melting point: 172-17-1;

NMR spectrum (DMS 0-d ₆ ) δ ppm: 1.5-1.7 (3H, ra), 1.7-1.85 (2H, m), 1.9-2.0 (1 H, m), 2.66 (1 H, dt, J = 16 Hz, J = 4 Hz), 2.1-2.9 (2 H, m). 3.2 (4H, m), 3.25-3.45 (3H, nd), 3.45-3.65 (2H, m), 3.88 (3H, s), 4 07 (1 H, d, J = 12 H z), 6-69 (1 H, t, J = 7 H z), 6-76 (1 H, d, J = 4 H z), 6 90 (1H, d, J = 8Hz), 6.97 (1H, d, J = 7Hz), 7.06 (1H, t, J = 8Hz), 7. 8 1 (1 H, t, J = 6 Hz), 8.00 (1 H, d, J = 4 Hz), 10 0.3-1 0.6 (1 H, b r. S):

IR spectrum (KBr) v ", cm- ¹ : 340 3.33 39, 256 2 .246 5.1 64 2.

Example 4 6

 3- [4- (2,4-dioxothiazolidine-1-3-yl) butyl] 1,2,3,4,4a, 5,6-hexahi draw 1 H-Virazino [1,2—a] Quinoline hydrochloride (Exemplary compound number: 2-3)

 (a) 3— [4- (2,4-dioxothiazolidine-1-yl) butyl] one

2.3, 4, 4a, 5, 6—Hexahi Draw 1 H-Virazino [i, 2-a) Quinoline

 2,3,4,4a, 5,6-Hexahydro 1H-Virazino [1,2-a] quinoline (105 mg) and 3- (4-bromobutyl) thiazolidine 1,2,4- Dione (140 mg) was dissolved in DMF (2 ml), and potassium carbonate (68 mg) was added, followed by stirring at 100 for 1 hour. After cooling, ethyl acetate was added, followed by washing with water, and the organic layer was dried using anhydrous sodium sulfate. The solvent obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (eluent: ethyl persulfate) to obtain the desired compound (198 mg, 99%) as a pale red oily substance. Was.

NM R spectrum _{(CDC 1 3) δ ppm:} .. 1. 45 - 2. 0 (6 H, m), 1 9 1 (. 1 Η, t J = 1 1 Η ζ) 2. 1 9 (1 Η, dt, J = 1 1 Η,, J = 3 Η ζ), 2.38 (2,, t, J = 7 ζ ζ), 2. 6-2.75 (1 Η, tn), 2 7 5-3.1 (5 Η, m), 3.67 (2, t, J = 7 Η).

3.75 (1Η, d, J = 1 11Η), 3.94 (2, s), 6.69 (1Η.t, J = 7ζ), 6.79 ( D, J = 8 Η ζ), 6.98 (1 Η d. J 7 7 Η), 7.08 (1,, t, J = 8 Η) 6.

 (b) 3— [4- (2,4-dioxothiazolidine-1-3-yl) butyl] -1,2,3,4,4a, 5,6-hexahidraw 1H—birazino [1,2 -a) Quinoline monohydrochloride

 3- [4- (2,4-dioxothiazolidine-1-yl) butyl] 1-2, 3.

4. 4a, 5,6-HexahiDraw 1H-Virazino [1.2-a] Quinoline (180 mg) is dissolved in a mixed solvent of ether (5 ml) and ethyl acetate (2 ml). , 4 N hydrogen chloride monoacetate solution (120 M1) in ^ acid ethyl chloride (1 ml) solution Was added dropwise. After stirring at room temperature for 30 minutes, the precipitated crystals were collected and dried to obtain the desired compound (144.6 mg. 73 3).

 Melting point: 1 76-18 1;

 NMR spectrum (DMS 0—cU) δ ppm: 1.5—1.8 (5H, m), 1.9–2.0 (2Η, m), 2.66 (1Η, dt) , J = 16Η, J = 5Η), 2.75-2.9 (2Η, m) 3.0-3.2 (4Η, m), 3.2 5-3. 4 5 (1 Η, η d). 3.45-3.6 (4,, m), 4.08 (1 Η, d, J = 9 Η), 4.2 1 (2 Η, s) 6.69 (1,, t, J = 7 Hz), 6.90 (1 Η, d, J = 8), 6.97 (1,, d, J = 7 Η), 7.06 (1 1, t, J = 8Η), 10.3-10.5 (1Η, br.s);

 IR spectrum (ν «·, cm- '): 2352, 1 752.16.678.

 Example 4 7

 3— [3— (2,4-dioxothiazolidine-1-3-yl) brovir] 1,2,3.4,4a, 5,6—hexahydro-1H-birazino [1,2, -a ] Quinoline fumarate (Exemplary compound number: 2_2)

 (a) 3— [3— (2,4-dioxothiazolidine-1-yl) provir] -2,3,4.4a, 5.6-hexahydro-1H-virazino [1, 2-a] quinoline

 2,3,4,4a, 5,6-Hexahydro 1H-Virazino [1,2-a] quinoline (140 mg) and 3- (3-bromopropyl) thiazolidine-2. 4-Dione (178 mg) was reacted in the same manner as in Example 46a and worked up to give the desired compound (206 mg. 80%) as an oil.

NM R spectrum _{(CDC l 3) S ppm:} .. 1 6 - 1 9 5 (5 H, m), 2. 1 2 (1 H, dt, J = 1 1 Η ζ, J = 3 Η ζ) 2.42 (2,, t, J = 7 Η). 2. 6-3.05 (6 Η .m), 3.7-3.8 (1 Η. Η d). 3- 7 4 (2 Η. T, J = 7 Η), 3.91 (2 Η, s), 6.69 (1,, t. J = 7 Η), 6.78 (1 Η , d. J = 8 Η ζ), 6.98 (1 Η, d. J = 7 Hz). 7.08 (1 H, t, J = 8 Hz).

 (b) 3 — [3 — (2.4-dioxothiazolidine-1-yl) provir]-2.3, 4, 4 a, 5, 6 —hexahi draw 1 H-Virazino [1, 2 -a) Quinoline fumarate

 3 — [3 — (2,4-Dioxothiazolidine-1-yl) provir] 1, 2,3,4,4a.5,6—Hexahydro 1 H—Virazino [1,2—a 〗 Quinoline (100 mg) was dissolved in methanol (5 ml), and this solution was added to a methanol (2 ml) solution of fumaric acid (34 mg) with stirring at room temperature. Stir for 5 minutes. The solvent was distilled off under reduced pressure, ether (15 m 1) was added to the obtained residue, and the mixture was subjected to ultrasonic treatment for 1 hour, and the precipitated crystals were collected to obtain the desired compound (105.8) mg, 79%).

 »Point: 1 6 3 — 1 6 5;

NMR spectra (DMS 0-d ₆ ) δ ppm: 1.55-1.65 (1 H, m), 1.70 (2, quint, J = 7), 1. 7 8 (2Η, t, J = 1 11 1), 1.85 (1Η, ddd, J = 13 3, J = 6Η, J = 3Hz), 2.04 (1 Η, dt, J = 1 1 Η, J = 3 Η), 2.34 (1 Η,. J = 7 Η), 2.5 5-2.6 2 (1 Η, m ), 2.65 (1st, dd. J = 12 Hz, J = 3 Η), 2.75-2.95 (4, m), 3.57 (2nd) t, J = 7 Η), 3.77 (1, d, J = 1 Η), 4.16 (2, s), 6.60 (1 t t, J = 7 Η), 6.62 (2 Η, s), 6.80 (1 Η. D, J = 8 Η), 6.91 (1,, d, J = 7 Η), 6. 9 9 (1 Η. T, J = 7 Η ζ);

IR spectrum (KBr) i ,,, cm— ¹ : 2549, 2463, 1746, 1679 ο

 Example 4 8

3 — [5 — (2, 4 — dioxothiazolidine-1-3-yl) pentyl] 1, 2, 3.4, 4 a, 5.6 — hexahi draw 1 H — virazino [1, 2-a] Quinoline monohydrochloride (Exemplary compound number: 2-4) 2,3,4,4a, 5,6-Hexahydro 1H-Virazino [1.2-a〗 quinoline (137 mg) and 3- (5-bromopentyl) thiazolidine —Dione (194 mg) was reacted in the same manner as in Example 46a and 46b and worked up to give the desired compound (180 mg. 71%).

 »Points: 1 6 1 — 1 6 4 at;

NMR spectrum _{(DMSO- d 6) δ ppm:} ..... 1 2 - 1 3 5 (2 H, m), 1 5 - 1 8 (5 H, m), 1 9 - 2. 0 (1 H, m) .2.66 (1 H, dt .J = 16 Hz, J = 5 Hz), 2.75-2.9 (2 H .m), 3.0-3. 1 5 (4H, m), 3.2-3.4 (1H, nd), 3.45-5-3 • 6 (4H.m) .4.07 (1H, d, J = 10 Hz), 6.69 (1H, t. J = 7Hz), 6-90 (1H, d, J = 8Hz), 6.97 (1H, d, J = 7 Hz), 7.06 (1H, t, J = 8 Hz), 10.4-10, 6 (1H, br.s);

IR vector (KB i vu C m- ¹ : 245 2, 174 1, 1 677 7 Example 4 9

 3— [4- (5,5-dimethyl-2,4-dioxothiazolidine-13-yl) butyl] 1-2,3.4,4a, 5,6-hexahydro 1H—Virazino [1 , 21-a] quinoline monohydrochloride (Exemplary Compound No .: 2-27)

 2.3,4.4a.5,6-Hexahi draw 1 H-Virazino [1,2-a] quinoline (163 tng) and 3- (4-bromobutyl) -1,5-dimethyl Thiazolidin-one 2.4-dione (243 mg) was reacted in the same manner as in Examples 46a and 46b and worked up to give the desired compound (149.8 mg, 56 ¾) was obtained.

 K point: 15 5-16 0;

NMR spectrum _{(DMSO- d 6) δ ppm:} ..... 1 5- 1 8 (5 H, m) 1 6 6 (. 6 H s), 1 9 - 2. 0 (1 H, m) , 2.66 (1 H, dt, J = 16 Hz, J = 5 Hz), 2.73-2.9 (2 H, m). 2.9-3.2 (4 H m), 3.2-3.4 (1 H, nd). 3.43-3.63 (4 4.07 (1 H, d, J = 1 1 H z). 6.69 (1 H, t, J = 7 H z). 6.90 (1 H, d, J 6.97 (1 H, d. J = 7 H z), 7.06 (1 H, t, J = 8 H z), 10 .7-10 .9 (1 H , br. s);

IR spectrum (KB ivu C m- ¹ : 2547, 2458, 1747 Example 50

 3-[4-1 (5-Isoprovir-1,2,4-dioxothiazolidine-1-yl) butyl 3 — 2,3,4,4a, 5,6—Hexahidraw 1 H—Virazino [1 , 21-a] Quinolin monohydrochloride (Exemplary Compound No .: 2-34)

 2,3,4,4a, 5,6-Hexahydro-1H-virazino [1,2-a] quinoline (186 mg) and 3- (4-bromobutyl) -15-isobrobi Ruthiazolidin-1,2,4-dione (305 mg) was reacted in the same manner as in Examples 46a and 46b, and post-treated to give the target compound (96.4 mg, 24%).

 »Points 1 64-1 67 * C;

NMR spectrum (DMS 0—d ₆ ) δ ppm: 0.88 (3H, d, J = 7 Hz), 0.99 (3H, d, J = 7 Hz). 5-1.75 (5H, m). 1.91-2.0 (1H, m), 2.66 (1H, dt, J = 16Hz, J = 5Hz), 2.75-2.9 (2 H, m), 3.0-3.2 (4 H, m), 3.2-3.4 (2 H, nd), 3.45-3.6 (2H, nd), 4.08 (1H, d.J = 9Hz), 4.71 (1H, d.J = 4Hz), 6.70 (1H, t, J = 7 Hz), 6.90 (1 H, d, J = 8 Hz), 6.98 (1 H, d. J = 7 Hz). 7.06 (1 H, t, J = 8 H z). 10. 35-10 .55 (1 H, br. S);

IR spectrum Honoré (KB r) i - ,, c m '1: 2 55 6. 2 4 64, 1 747, 1 67 9.

 Example 5 1

3— (3—phthalimidobuchi building) 1 2, 3.4, 4a, 5.6—hexazide Rho 1 H—Virazino [1,2—a] Quinoline

 (Exemplary compound number: 2-45)

 2,3,4,4a, 5.6-Hexahydro 1H-birazino [1.2-a] quinoline (240 mg) and N- (3-bromopropyl) phthalimid (34 2 mg) was reacted in the same manner as in Example 1a and worked up to give the desired compound (453 mg, 95%) as a yellow oily substance.

. NMR spectrum _{(CDC 1 3) δ p pm} : 1 6- 2. 0 (7 H, m), 2. 0 5 - 2. 2 (. 1 Η m), 2. 4 5 (2 Η, t , J = 7 Η ζ) .2.5-3.0 (6 Η, m), 3.68 (1 Η, d, J = 13 Η), 3.79 (2 Η, t, J = 7 Η), 6.67 (1 t, t. J = 7 Η), 6.73 (1 Η. D. J = 8 Η), 6.95 (1 d, d J = 7 Η), 7.06 (1,, t. J = 8 Η), 7.6 5-7.75 (2,, m), 7.8-7.9 (2 Η. M). Example 5 2

 3— (2—phthalimidethyl) 1, 2,3,4,4a, 5,6—hexahydro-1H-birazino [1,2—a] quinoline

 (Exemplary compound number: 2-44)

 2,3,4,4a, 5,6-Hexahydro-1H-birazino [1,2-a] quinoline (410 mg) and N- (2-bromoethyl) phthalimid (5 60 mg) was reacted in the same manner as in Example 1a and worked up to give the desired compound (580 mg, 74%).

 »Point: 1 2 9—1 3 2 * C;

NM R spectrum _{(CDC l 3) S p pm} :... 1 6 5 - 1 9 5 (2 H, m), 1 9 9 (1 H, t, J = 1 1 Η ζ), 2. 2 7 (1 Η, dt, J = 11 Hz, J = 3 Η), 2.66 (2 Η, t, J = 6 Η), 2.7-3.0 (5 Η. M ), 3.0—3.15 (1Η, m). 3.70 (1Η, d. J = 12 2), 3.86 (2Η, t, J = 7Η) ), 6.67 (1 Η. T. J = 7 Η), 6.76 (1 Η, d, J = 8 Η). 6.96 (1,, d. J = 7 Η) )), 7.06 (1 Η. t. J = 8 Η ζ), 7.65-7.75 (2 Η .m), 7.8-7 9 (2 H, m):

 IR spectrum (KBr) v „., Cm- ': 1770.10.1709.

 Example 5 3

 3- (4-benzamidebutyl) 1,2,3,4,4a, 5,6-hexahydro-1H-birazino [2,1-c] 1-1,4-benzoxazine monohydrochloride

 (Exemplary compound number: 1-130)

 2,3,4,4a, 5,6-Hexahi Draw 1 H-Virazino [2,1-c]-1,4,1-benzoxazine and N- (4-promobutyl) phthalimid Example la, Reference example 1. The reaction was carried out in the same manner as in Example 2a and then in 2b, followed by post-treatment to give the target compound as colorless needles.

 »Point: 1 89-191.

 Example 54

 3- (4-phenylcarbamoylbutyl) 1,2,3,4,4a, 5,6-hexahi draw 1H-Virazino [1,2, a] quinoline dihydrochloride

 (Exemplary compound number: 3-3)

 2,3,4,4a, 5,6-Hexahydrol 1H-Virazino [1,2-a] quinoline (162 mg) and 4-phenylcarbamoylbutyl bromide (220 mg ) Was dissolved in isopropanol (15 ml), sodium carbonate was added, and the mixture was heated and passed for 8 hours. After cooling, the mixture was filtered, the solvent was distilled off under reduced pressure, water was added to the resulting residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (solvent: 10% ethanol / methylene chloride solution), and an excess of 10 N hydrochloric acid / methanol solution was added. It was left at room temperature for 30 minutes. The solvent was distilled off under reduced pressure, and the obtained residue was recrystallized from ethanol to give the desired compound (230 mg, 61%) as colorless needles.

 »Point: 2 1 8 (decomposition);

NM R spectrum _{(DMS 0- d 6) δ ppm} :.. 1. 5- 1. 7 (3 H, m), 1 7 - 1 9 (2 H, m), 1. 9 one 2.0 ( 1 H. M). 2.40 ( 2 H, t, J = 7.3 Hz), 2.6-2.9 (3H, m), 3.0-3.2 (4H, m), 3.4-3.6 ( 3.06 (1H.d, J = 11.9Hz), 6.69 (1H, t, J = 7.3Hz), 6.89 (1H, d, J = 8.6 Hz), 6.9-7.2 (3 H, m). 7.29 (2 H, t, J = 7.3 Hz, J = 8.6 Hz ), 7.45 (1H, br.s), 7.63 (2H, d, J = 7.9Hz), 10.0.08 (1H, s), 11.00 (1 H.br.s). Example 5 5

 (I)-3-(4-phthalimidbutyl) I 2,3,4.4a, 5,6-Hexahi draw 1H-Virazino [1,2-a] quinoline

 (Exemplary compound number: 2-46)

 (1) 1,2,3,4.4a, 5,6-Hexahydro-1H-birazino [1,21a] quinoline (0.71 g), N- (4-bromobutyl) phthalimid (1.07 g) and potassium carbonate (0.52 g) were reacted in the same manner as in Example 1 (a) and worked up to give the desired compound (1.26 g, 85%).

Optical rotation ^{_{([a] D 2 *)}} : one 6. 8 ° (C- 1. 08, E t OH); IR spectrum (Omicron Ita_〇 _{1 3) ν ·, c m-} 1: 2 946, 2 824, 1771, 1712, 1602;

NM R spectrum _{(CDC 1 3) δ ppm:} . 1. 53 - 1. 95 (6 H, m), 1 9 2 (. 1 H, t J = 1 0. 9 H z), 2. 1 8 (1 H, dt, J =

2.9 Hz, J = 11.2 Hz), 2.38 (2H, t, J = 7.4 Hz) .2.65-2.75 (1H, m), 2.75-2.95 (3 H, m), 2.95-

3.08 (2H.m), 3.65-3.80 (1H, nd), 3.74 (2H.t, J = 7.0Hz). 6.68 (1H, t, J = 7.2 Hz), 6.78 (1 H, d. J = 8.2 Hz). 6.97 (1 H. d, J = 7.2 Hz), 7.08

(1H, t, J = 8.2Hz), 7.67-7.76 (2H, m). 7.80-7.90 (2H, m).

 Example 5 6

(+) — 3— (4-phthalimidobutyl) i 2.3, 4.4 a, 5, 6 1H-Virazino [1, 2 — a] Quinoline

 (Exemplary compound number: 2-4 6)

 (+)-2,3,4.4a.5,6-hexahydro-1H-birazino [1,21a] quinoline (0.90 g), N- (4-bromobutyl) phthalate The target compound (1.57 g, 84%) was reacted with mid (1.41 g) and lithium carbonate (0.66 g) in the same manner as in Example 1 (a), followed by post-treatment. ).

Specific rotation ([a: + 9.7 ° (C = 1.00, EtOH)); IR spectacle (KBr)! / ·, Cm ” ¹ : 294948, 2882 5, 1 7 7 2,

1 7 1 3, 1 6 0 5;

NM R spectrum _{(CDC 1 3) 5 ppm:} .... 1 5 3 - 1 9 6 (. 6 H m) 1 9 1 (1 H, t, J = 1 0. 9 H z), 2. 1 8 (1 H, dt, J =

2.9 Hz, J = 1 1.2 Hz), 2.38 (2H, t, J = 7.4 Hz) .2.65-2.75 (1H, m) , 2.75-2.95 (3 H, m), 2.95-

3.09 (2H, m), 3.60-3.85 (1H, nd), 3.74 (2H, t, J = 7.OHz), 6.69 (1 H, t. J = 7.2 Hz), 6.78 (1H, d, J = 8.2Hz), 6.97 (1H, d, J = 7.2Hz) , 7.08

(1H, t, J = 8.2Hz), 7.68-7.75 (2H, m), 7.82-7.88 (2H, m).

 Example 5 7

 (1-) 1-3- (2-phthalimidethyl) 1-2,3,4.4a.5,6-hexahi draw 1H-virazino [1,2—a] quinoline

 (Exemplary compound number: 2-44)

 (-)-2,3,4.4a, 5,6-hexahydro-1H-birazino [1.2-a] quinoline (0.822 g), N- (2-bromoethyl) Phthalimid (1.

2 g) and potassium carbonate (0.61 g) were reacted in the same manner as in Example 1 (a), followed by post-treatment to obtain the desired compound (0.93 g, 59%). Was.

Specific rotation ([α] ^24.): One 3. 9 ° (C = 1 0 2. CHC 1 3.); IR spectrum (KB r) V ... cm " 1: 2 9 3 2, 2 8 1 8, 1 7 6 7. 17 08, 16 04;

NMR spectrum _{(CDC 1 3) 5 ppm:} .. 1 6 5 - 2. 0 5 (2 H, m), 1 9 9 (1 H, t, J = 1 0. 8 H z), 2. 2 7 (1 H, dt, J = 3.1 H z. J = 1 1.3 H z), 2.66 (2 H, t, J = 6.6 H z), 2-70-3 0 0 (5H, m), 3.00-3.15 (1H, m), 3.70 (1H, d, J = 11.8 Hz), 3.86 (2 H, t, J = 6.5 Hz), 6.67 (1 H, t, J = 7.3 Hz), 6.76 (1 H, d, J = 8.2 H z), 6.96 (1 H. d, J = 7.3 H z). 7.06 (1 H. t. J = 8.2 H z), 7.68-7.79 (2H, m), 7.81-7.90 (2H, m).

 Example 5 8

 (+) — 3— (2-phthalimidethyl) 1, 2,3,4,4a, 5,6—hexahydro 1 H-birazino [1,2, a] quinoline

 (Exemplary compound number: 2-44)

 (+)-2,3,4,4a, 5,6-hexahydro-1H-birazino [1,2-a] quinoline (0.75 g), N- (2-bromoethyl) By reacting phthalimid (1.11 g) and lithium carbonate (0.555 g) in the same manner as in Example 1 (a) and performing post-treatment, the target compound (1.21 g, 84 %).

Specific rotation ^{(. [Α] 2 *)} : + 4. 5 ° (. C = 1 0 0, CHC 1 3); IR spectrum Honoré ^{(KB r) V cm "1} : 2 9 3 2, 2 8 1 9, 1 7 6 7, 1 7 0 9.1 6 0 4;

NMR spectrum (CDCl ₃ ) S ppm: 1.65-2.05 (2H.m), 1.99 (1H, t.J = 10.8 Hz), 2.2 8 (1 H, dt, J = 3.1 Hz. J = 1 1.3 Hz). 2.66 (2 H. T. J = 6.6 Hz), 2.70-3 0 0 (5H, m), 3.00-3.15 (1H, m), 3.71 (1H, d, J = 11.8 Hz), 3.86 (2 H. T, J = 6.5 Hz). 6.68 (1 H, t, J = 7.3 Hz). 6.76 (1 H, d, J = 8.2 H 6.97 (1 H, d, J = 7.3 H z) .7.06 (1 H, t, J = 8.2 H z), 1.67-7.78 (2H.m) .7.82-7.91 (2H.m). Example 5 9

 (I) I 3— [4— (5,5-Dimethyl 2.4-dioxothiazolidin-1-yl) butyl] I, 2,3,4,4a, 5.6—Hexahi draw 1H—Viradino

 [1,2-a] quinoline monohydrochloride (Exemplary compound number: 2-27)

 (a) (—) 1 3— [4- (5,5-dimethyl-2,4-dioxothiazolidin-1-3-yl) butyl] 1,2,3,4,4a, 5,6—Hexahi draw 1 H—Virazino [1,2—a] quinoline

 (1) -2,3,4,4a, 5,6-Hexahi draw 1H-Virazino [1,21a] quinoline (0.31 g), 3- (4-bromobutyl) 1-5 , 5-Dimethylthiazolidine-2,4-dione (0.46 g) and lithium carbonate (0.23 g) were reacted in the same manner as in Example 46 (a), followed by post-treatment to obtain the desired compound. (0.53 g, 83%).

Specific rotation ([a] _D ): one 7.0 ° (C = 0.99. EtOH);

IR spectrum Tosore _{(CHC l 3) v ,,, cm-} '2 946. 2 824, 1 7

46, 1 6 8 1, 1 6 02;

NM R spectrum _{(CDC 1 3) δ ppm 1.} 46 -. 2. 00 (3 H, m), 1 7 0 (6 H, s), 1. 90 (2 H t, J = 1 0. 7 Hz), 2.18 (1H, dt, J = 3.1Hz, J = 1114Hz), 2.38 (2H.t, J = 7.3Hz), 2 65-3.08 (6 H, m), 3-65 (2 H. T, J = 7.1 Hz), 3.75 (1 H, dt, J = 2.6 Hz, J = 11.8 Hz), 6.69 (1H, t.J = 7.2Hz), 6.79 (1H, d, J = 8.2Hz), 6.98 ( 1 H. D, J = 7.2 Hz), 7.09 (1 H, t, J = 8.2 Hz).

 (b) (1)-3-[4-(5, 5-dimethyl-2.4-dioxothiazolidin-1-3-yl) butyl] 1. 2, 3, 4, 4 a. 5, 6-Hexahydro 1 1 H—birazino [1.2—a] quinoline monohydrochloride

1,3- (4-1- (5.5-dimethyl-2.4-dioxothiazolidin-1-3-yl) butyl) -1-2.3,4,4a.5,6-hexahydro 1H-birazino 12

[1.2-a] Quinoline (0.46 g) was reacted in the same manner as in Example 46 (b) and worked up to give the desired compound (0.39 g. Quantitative). .

 Specific rotation ([α]: 10.2 ° (C = 1.00, EtOH)): Melting point: 169-172;

 IR spectrum (KBr) Vcm ": 2930, 2559, 246.67.1743, 1683;

■ NMR Spectrum (DMS O-d ₆ ) δ ρ ριη: 1.54-1.73 (5 Η, m), 1.66 (6 Η, s), 1.93-1. 99 (1 Η, m), 2.66 (1 Η, dt, J = 4.5 Η ζ.J = 16.2 Η ζ), 2.76-2.86 (2 ,, m), 2 9.5-3.20 (4 ,, m), 3.20-3.40 (1 Η η d), 3.40-3.60 (4 ,, m). (1Η, d, J = 11.3 1.Η), 6.69 (1Η.t, J = 7.3Η), 6.90 (1Η, d, J = 8.3Hz ), 6.97 (1,, d, J = 7.3 Η), Η · 06 (1 Η. T, J = 8.3 Η), 10.6 3 (1 Η, brs) _e

 Example 6 0

 (+) — 3— [4-(5.5-dimethyl-2,4-dioxothiazolidine-1-yl) butyl] -1 2.3, 4, 4a, 5, 6-hexahidraw 1 H -Virazino

 [1,2—a] quinoline monohydrochloride (Exemplary compound number: 2-27)

 (a) (+) — 3— [4-(5,5-dimethyl-2,4-dioxothiazolidin-1-3-yl) butyl] 1, 2,3.4,4 a, 5,6—Hexahi draw 1 H—Virazino [1, 2— a] Quino phosphorus

 (+)-2,3,4,4 a.5,6-hexahydro 1H-virazino [1.2-a] quinoline (0.19 g), 3- (4-bromobutyl) -1 5. 5-Dimethylthiazolidine-1-2.4-dione (0.34 g) and lithium carbonate (0.17 g) were reacted in the same manner as in Example 46 (a), and were post-treated to give the desired compound (0. -31 g. 79%).

Specific rotation ^{(. [Α] 2 *)} :! + 8. 5 ° (. C = l 00. E t 0 H); IR spectrum (CHC 1 3) / "' c m-': 2 94 6 . 2 824. 1 7 47, 1 68 1. 1 60 2;

NM R spectrum _{(CDC 1 3) δ ppm:} .. 1. 45 - 1 99 (3 H, m), 1 7 0 (6 H, s), 1. 90 (2 H, t, J = 1 0 7 Hz), 2.18 (1 H, dt. J = 3.2 Hz. J = 11.4 Hz), 2.38 (2H, t, J = 7.2 Hz 2.65-3.08 (6H, m), 3.65 (2H, t, J = 7.2Hz), 3.75 (1H, dt, J = 2.6H) z, J = 11.9 Hz), 6.69 (1 H, t, J = 7.3 Hz), 6.79 (1 H, d, J = 8.2 Hz), 6.98 (1H, d. J = 7.3Hz), 7.08 (1H, t, J = 8.2Hz)

 (b) (+) — 3— [4- (5,5-dimethyl-2.4-dioxothiazolidin-1-3-yl) butyl] —1,2,3,4,4a, 5,6—Hexahi draw 1 H-birazino [1, 2— a] quinoline monohydrochloride

 (+) — 3— [4- (5,5-dimethyl-2,4-dioxothiazolidine-1-yl) butyl] 1-2,3,4,4a, 5.6-hexadraw 1H —Virazino

 [1,2-a] quinoline (0.28 g) was reacted in the same manner as in Example 46 (b) and worked up to give the desired compound (0.30 g, quantitative).

Specific rotation ([α]. ²⁴ ): + 10.5 ° (C = 1.00, EtOH); Melting point: 169-172;

IR spectrum (KBr) V ... cm " ¹ : 2931, 25553, 2462, 1744, 1679;

NMR spectrum (DMS 0-d ₆ ) δ ppm: 1.54-1.74 (5H, m), 1.66 (6H, s). 1.94-1.99 (1H , m), 2.66 (1H.dt, J = 4.6Hz, J = 16.1Hz), 2.76-2.84 (2H, m), 2.95- 3.20 (4 H .m), 3.20-3.40 (1 H, nd), 3.40-3.60 (4 H, m). 4.07 (1 H, d, J = 12.6 Hz), 6.69 (1 H, t, J = 7.3 Hz). 6.90 (1 H, d, J = 8.3 Hz). 6.97 (1 H, d, J = 7.3 H z). 7.06 (1 H, t, J = 8.3 H z). 10.0.9 (1 H. Brs) ₀ Example 6 1

 (I) I 3— [4- (2,4-Difluorobenzamide) butyl] I, 2,3,4,4a, 5,6-Hexahydro-1H—Virazino [1,2— a] Quinoline monohydrochloride (Exemplary compound number: 1-155)

 (a) (—) 1—3— [4- (2,4-difluorobenzamide) butyl] 1,2,3,4,4a, 5,6-hexahi draw 1H-Virazino [1, 2—a] Quinoline

 (1-)-3- (4-aminobutyl) -1,2,3,4,4a, 5,6-hexahydro 1 H-birazino [1,2-a] quinoline (0.30 g), 2,4-Difluorobenzoyl chloride (0.16 ml) and triethylamine (0.19 ml) were reacted in the same manner as in Example 2 (a) and worked up to give the desired compound (0.1%). (36 g, 78%).

Specific rotation ^{([α] 2 <.)} : One 9. 2 ° (C = 1. 0 1, E t OH); IR spectrum _{(KB r) V .. x cm} "1: 32 70, 2 9 31 1, 2859, 2 807, 2 77 1, 1 647, 1 62 0.10.1 603;

NM R spectrum _{(CDC 1 3) δ ppm:} 1. 56 - 1. 90 (7 H, m), 2. 1 8 (1 Η, dt, J = 3. 2 Η ζ, J = 1 1. 5 2.41 (2 Η, t, J = 6.8 Η), 2.65-3.05 (6 Η, m), 3.5 1 (2 q, q, J = 5 9 Η), 3.72-3.77 (1 ,, m), 6.69 (1 Η, t, J = 7.3 Η), 6.77-7.15 (6 Η, m), 8.05-8.15 (1Η, m).

 (b) (1)-3-[4-1 (2,4-difluorobenzamide) butyl] 1, 2, 3, 4.4 a. 5, 6-hexahi draw 1 H-virazino [1, 2-a] Kino

J

(1) 1—3— [4— (2,4 difluorobenzamide) butyl] 1—2, 3.4, 4 a. 5, 6—hexahydro 1 H—Virazino [1.2— a] Quinolin (0 • 31 g) was reacted in the same manner as in Example 2 (b) and worked up to give the desired compound (0.25 g, 7496). Specific rotation ^{(. [Α] 2 *)} : one 9. l (C = 1 00, E t OH.); Mp: 1 6 0 - 1 6 5;

 I R Spectrum (KBr) V „« cm ”': 3246.29293, 2476, 16659, 1618.1602;

NMR scan base click preparative Honoré _{(DM SO- d 6) 5 p} pm:.. 1 5 3 - 1. 68 (3 H, m), 1. 7 5 - 1 82 (2 H, m), 1. 95 -2.00 (1 H .m). 2.67 (1 H, dt, J = 4.6 Hz, J = 16.1 Hz), 2.76-2.86 (2 H, m), 3.00-3.19 (4 H, m), 3.29 (2 H, dd, J = 6.7 Hz. J = 12.9 Hz), 3.30- 3.40 (1H, nd), 3.54 (2H, t, J = 12.4Hz), 4.08 (1H, d, J = 11.1Hz), 6. 6 9 (1H, t, J = 7.3Hz), 6.90 (1H, d, J = 8.3Hz), 6.98 (1H.d.J = 7.3H) z), 7.06 (1 H, t, J = 8.3 H z), 7.17 (1 H, dt, J = 2.3 H z, J = 8.4 H z), 7. 36 (1 H, ddd, J = 2. OH z, J = 9.3 H z, J = 10.5 H z), 7.70 (1 H, dt, J = 6.9 H z, J = 8.4 Hz), 8.40 (1 H. T, J = 4.8 Hz). 10.78 (1 H, brs).

 Example 6 2

 (+) 1-3-[4-(2.4-difluorobenzamide) butyl] 1, 2, 3, 4, 4 a, 5, 6-Hexahi draw 1 H-virazino [1, 2-a ] Quinoline monohydrochloride (Exemplary compound number: 1-155)

 (a) (+) — 3— [4- (2,4-diflurobenzamide) butyl] -1-2.3,4,4a.5,6-Hexahydro-1H—birazino [1, 2—a] Quinoline

(+) — 3— (4-aminobutyl) 1 2.3.4, 4a, 5.6—Hexahydro 1 H—Virazino [1,2—a] quinoline (0.30 g ), 2,4-difluorobenzoyl chloride (0.15 ml) and triethylamine (0.16 ml) were reacted in the same manner as in Example 2 (a), followed by post-treatment to give the desired compound ( 0.4 1 g. 89%). Specific rotation (. ^{[Shed] 24): + 8. 2 °} (. C = 1 0 0. E t OH); IR spectrum (Κ Β Γ) ν ··, c m- ': 3 2 6 9 . 2 9 3 1, 2 8 5 9

, 280 7, 277 1, 1 6 4 6. 16 2 0, 16 0 3;

NMR spectrum (CDCl ₃ ) 5 ppm: 1.55-1.94 (7H, m), 2.18 (1H, dt, J = 3.2 Η, J = 11.5 Η), 2.41 (2 Η, t. J = 6.8 ζ) .2.65-3.03 (6 Η, m), 3.51 (

2 Η, q, J = 5.9 Η), 3.7 1-3.77 (1 ,, m), 6.69 (1

T, J = 7.3 Η), 6.77-7.1 1 1 (6 ,, m), 8.05-8.

1 4 (1Η, m).

 (b) (+) 1 3— [4- (2,4-difluorobenzamide) butyl]-

2,3,4,4a, 5,6-Hexahi draw 1H-Virazino [1,2—a] quinoline monohydrochloride

 (+)-3-[4-(2, 4-difluorobenzamide) butyl] 1 2.3, 4.4 a, 5, 6-hexahydro 1 H-virazino [1, 2- a] Quinoline (0-38 g) was reacted in the same manner as in Example 2 (b) and worked up to give the desired compound (0.41 g, quantitative).

Specific rotation ([α]; ² «): + 8.2 ° (C = 1.00, Et0H);

»Point: 1 5 4-1 5 6;

IR spectrum Honoré ^{(KB ri / w C m 1} : 3 2 4 4. 2 94 0, 2 4 7 6, 1 6 5 9, 1 6 1 8, 1 6 0 1;

NMR spectrum _{(DMSO- d e) 5 ppm:} ..... 1 5 3 - 1 6 7 (3 H, m), 1 7 5 - 1 8 3 (2 H, m), 1 94 - 2. 0 0 (1 H, m), 2.67 (1 H, dt, J = 4.6 H z. J = 16.1 H z), 2.76 6-2.86 (2 H, m), 3.00-3.20 (4 H, m) .3.29 (2 H, dd, J = 6.7 Hz. J = 12.9 Hz), 3.3 0-3.40 (1 H, nd),

3.54 (2H.t, J = 12.4Hz), 4.08 (1H, d, J = 11.4Hz), 6.70 (1H.t, J = 7.3 Hz), 6.90 (1 H, d. J = 8.3 Hz). 6.98 (1 H. D, J = 7.3 Hz). 6 (1 H.t.J 7.17 (1 H, dt, J = 2.6 H z. J = 8.5 H z), 7. 36 (1 H, ddd, J = 2. OH z, J = 9.3 Hz, J = 10.5 Hz), 7.70 (1 H, dt, J = 6.8 Hz, J = 8.5 Hz), 8.4 1 (1H, t, J = 5.OHz), 10.75 (1H, brs).

 Example 6 3

 (1) 1-3 (4-benzamide butyl) 1,2,3,4,4a, 5,6-hexahi draw 1H—Virazino [1,2—a] quinoline monohydrochloride

 (Exemplary compound number: 1-125)

 (a) (—) 1—3— (4—benzamide butyl) 1,2,3.4,4a, 5,6—Hexahi draw 1H—Virazino [1,2—a] quinoline

(1-) 1-3- (4-aminobutyl) -1,2,3,4.4a, 5,6-hexahydrid-1H-birazino [1,2-a] quinoline (0.30 g ), Benzoyl chloride (0.15 ml) and triethylamine (0.19 ml) were reacted in the same manner as in Example 2 (a) and worked up to give the desired compound (0.37 g, . 88%) was obtained specific rotation ^{([<Σ] 2 *)} : - 8. 9 ° (C = 1. 04, E t OH); IR spectrum ^{(KB r) V cm "1} : 32 78 , 2930, 2860, 2810, 1638, 1602;

NM R spectrum _{(CDC 1 3) δ ppm:} ... 1. 55 - 1 80 (5 H, m), 1. 80 - 1 86 (1 Η, m), 1. 89 (1 Η t, J = 1 0.9 Η)), 2.18 (1,, dt, J = 3.2 Η,, J = 1 1.3 Η), 2.42 (2,, t, J = 6 2.69 (1 st, ddd, J = 16.OHz, J = 5.2 Hz. J = 3.7 Hz). 2.75-2.92 (3 H, m), 2.92--3.02 (2H.m) .3.51 (2H, q, J = 6.1Hz), 3.74 (1H, dt, J J = 1 2.3 Hz), 6.64 (1H, brs to 6.70 (1 H, t, J = 7.3 Hz), 6.79 (1 H. D, J = 8.1 Hz), 6.98 (1 H, d, J = 7.3 Hz). 7.07 (1 H, t, J = 8.1 Hz), 7.35-7.50 (3H.m), 7.75 (2H, d, J = 6. 7 H z) „

 (b) (I) 1-3 (4-benzamide butyl) 1,2,3,4.4a, 5,6-hexahidraw 1H-Virazino [1,2, a] quinoline monohydrochloride

 (1)-3-(4 Benzamide butyl) 1 2.3.4, 4a, 5, 6-hexahydro-1H-birazino [1, 2-a] quinoline (0.35 g) was reacted in the same manner as in Example 2 (b) and worked up to give the desired compound (0.31 g, 80%).

Specific rotation ([H]. ²⁴ ): -9.2 ° (C = 1.00, Et0H); Melting point: 176—179;

IR spectrum (Κ Β ι ν, ·, cm_ l: 3306, 2944. 2587, 2473, 1 655, 1 602. 1578;

NMR spectrum (DMS 0- _ds ) δ ppm: 1.55-1.67 (3H, m), 1.75-1.83 (2H, m), 1.95-1.99 (1 H, m), 2.66 (1H, dt, J = 4.5Hz, J = 16.lHz), 2.76-2.87 (2H.m), 3-00- 3.20 (4H, m), 3.24-3.45 (3H, m), 3.52-3.58 (2H, m), 4.07 (1H, d, J = 1 J-7.3 Hz), 6.90 (1H, d, J = 8.3Hz), 6.97 (1H, t. d, J = 7.3 Hz), 7.06 (1 H, t.J = 8.3 Hz), 7.47 (2H, t, J = 7.3 Hz), 7.53 (1 H. T, J = 7.3 Hz), 7.87 (2 H, d, J = 7.3 Hz), 8.57 (1 H, t, J = 5.5 Hz) , 10.70 (1H, brs).

 Example 64

 (+) — 3— (4-benzamide butyl) 1 2. 3. 4, 4a, 5, 6—Hexahi Draw 1 H—Virazino [1,2—a] quinoline monohydrochloride

 (Exemplary compound number: 1-25)

 (a) (+)-3-(4-Benzamide butyl) 1-2,3,4,4 a. 5,6-Hexahi draw 1 H -Virazino [1,2, -a] quinoline

(+) — 3— (4-aminobutyl) -1-2.3,4,4a, 5,6-hexahydrid Example 1 (a) 1H-birazino [1.2-a] quinoline (0.24 g), benzoyl chloride (0.11 ml) and triethylamine (0.13 ml) were prepared. was reacted in the same manner as, by post, the object compound (0. 2 9 g, 86% ) the resulting specific rotation ^{([α] 24.):} + 1 0. 1. (C = l.OO.EtOH); IR spectrum (KBr) ι, ·, cm- ': 3276, 2930, 2861, 2810, 1637.1602 ;

NMR spectrum (CDCl ₃ ) 5 ppm: 1.55-1.80 (5H, m), 1.80-1.86 (1H, m), 1.89 (1Η, t) , J = 10.9 Η ζ), 2.18 (1,, dt. J = 3.2 Η, J = 11.3 2.). 2.42 (2 Η. T, J = 6.8 Η ζ), 2-69 (1 Η, ddd, J = 1 6.Ο Η ζ, J = 5.2 Η ,, J = 3.7 Η ζ), 2.75-2.92 ( 3 Η, m), 2.92-3.02 (2 Η, m), 3.50 (2 q, q, J = 6.1 Η ζ). 2.8 Η ,, J = 1 2.3 Η ζ), 6-65 (1 Η, brs), 6.70 (1 Η, t, J = 7.3 Η), 6.78 (1 Η, d, J = 8.1 Hz), 6.98 (1Η, d. J = 7.3 Hz), 7.06 (1H, t, J = 8.1 Hz), 7 37-7.5 1 (3H, m), 7.75 (2H, d, J = 6.7Hz).

 (b) (+) — 3— (4-benzamide butyl) 1,2,3,4.4 a, 5,6-hexahi draw 1 H—Virazino [1,2—a] quinoline monohydrochloride

 (+) — 3— (4-benzamide butyl) 1, 2, 3, 4, 4a, 5, 6—hexahydro 1 H—birazino [1.2-a] quinoline (0.27 g) was reacted in the same manner as in Example 2 (b) and worked up to give the desired compound (0.30 g, quantitative).

Specific rotation ^{([α] 26.):} + 8. 6 ° (. C = l 02. E t OH); » point 1 7 9 - 1 8 1;

IR spectrum (KBr) ... cm " ¹ : 3303, 2943, 2577, 2469, 16.53.1602, 1578; 29

NMR spectrum (DMSO—cU) δ ppm: 1.54-1.67 (3H, m), 1.74-1.82 (2H, m), 1.9 5-1.9 9 (1 H, m) .2.66 (1 H, dt, J = 4.5 Hz, J = 16.1 Hz), 2.76-2-87 (2 H, m) , 3.00-3.20 (4H, m), 3.27-3.45 (3H, m), 3.52-3.58 (2H, m), 4.07 ( 1 H. D, J = 9.9 Hz), 6.69 (1 H, t, J = 7.3 Hz), 6.90 (1 H, d, J = 8.3 Hz), 6.97 (1H, d, J = 7.3Hz), 7.06 (1H, t, J = 8.3Hz), 7.47 (2H.t, J = 7.3) Hz), 7.53 (1H, t, J = 7.3Hz), 7.86 (2H, d, J = 7.3Hz), 8.56 (1H, t, J = 5.5 Hz), 10.5 (1H, brs).

 Example 65

 (I) I 3— [2— (2-Tenylamino) ethyl] I, 2,3,4,4a, 5,6-Hexahi draw 1H—Virazino [1.2—a] quinoline monohydrochloride

 (Exemplary compound number: 1-2 83)

 (a) (—) 1—3— [2— (2-Tenylamino) ethyl] 1,2,3,4,4a, 5,6—Hexahydro 1H—Virazino [1,2—a] quinoline

 (I) I-3- (2-aminoethyl) I, 2,3,4,4a, 5.6-Hexahydro 1H-Virazino [1,2, a] quinoline (0.27 g) , 2-tinol chloride (0.14 ml) and triethylamine (0.32 ml) were reacted in the same manner as in Example 2 (a) and worked up to give the desired compound (0.33 g, 84 g). %).

Specific rotation ^{([<Σ] 23.)} : One 8.5. (C = 1.00.EtOH); IR spectrum (KBr) V. „cm" ¹ : 3289, 2939, 2815.16,25,1602;

NM R scan base click Honoré _{(CDC 1 3) δ ppm:} . 1. 7 1 - 1. 94 (2 H, m) 2. 0 5 (1 Η, t, J = 1 0. 6 Η ζ), 2 3 3 (1 Η, dt. J = 3.2 Η 2, J = 11.4 Η). 2.63 (2 Η, t, J = 6. Ο Η), 2.68 -3.10 (6 ,, m). 3.56 (2 Η. Q, J = 5.6 Η). 30

80 (1H, dt, J = 2.7Hz, J = 11.6Hz), 6.72 (1H, t, J = 7.3Hz), 6.77 (1 H, brs), 6.8 1 (1H, d, J = 8.1 Hz), 6.98-7.13 (3H, m), 7.45-7.50 (2H, m

) o

 (b) (I) I-3— [2— (2-Tenylamino) ethyl] I, 2,3,4.4a, 5,6—HexahiDraw 1H—Virazino [1,2—a] quinoline

(I) I 3— [2— (2-Tenylamino) ethyl] I, 2,3.4,4a, 5,6-Hexahi draw 1H—Virazino [1,2—a] quinoline (0.2 9 g) was reacted in the same manner as in Example 2 (b) and worked up to give the desired compound (0.24 g, 77%).

 Specific rotation ([α] *): 1.2.2. (C = 00, Et0H) ft point: 185-191 (decomposition);

IR spectrum (KBr) V-, cm " ¹ 32 76, 2 938, 2920, 2590, 1645, 1620;

NMR spectrum (DMS 0-d ₆ ) δ ppm: 1.57-1.66 (1H, m), 1.80-1.99 (1H, m), 2.67 (1H, dt) , J = 4.5 Hz. J = 16.1 Hz). 2.81 (1 H, ddd, J = 5.5 Hz, J = 10.9 Hz. J = 16 2 H z), 2.91 (1 H, q, J = 10.3 H z), 3.00-3.20 (2 H, m), 3.20-3.60 ( 3 H, nd), 3.60-3.80 (4 H .m), 4.1 1 (1 H, d. J = 10 .0 Hz). 6-70 (1 H, t , J = 7.3 Hz) .6.91 (1H, d.J = 8.3H2) .6.98 (1H, d, J = 7.3Hz), 7.07 (1 H, t, J = 8.3 H z), 7.18 (1 H, t, J = 4.3 H z) 7.79 (1 H, d, J = 5.0 Hz) , 7.85 (1H, d, J = 3.4 Hz), 8.90 (1H, brs), 10.35 (1H, brs).

 Example 66

(+) 1 3— [2— (2—Tenylamino) ethyl] 1 2.3, 4, 4 a, 5 31

, 6—Hexahi Draw 1 H—Virazino [1,2—a] quinoline monohydrochloride

 (Exemplary compound number: 1-2 8 3)

 (a) (+)-3-[2 — (2-Tenylamino) ethyl] 1, 2.3.4, 4a, 5, 6-hexahi draw 1 H-Virazino [1,2 — a] quinoline

 (+) — 3— (2-aminoethyl) 1, 2,3,4,4a, 5,6-hexahydro 1 H—Virazino [1,2—a] quinoline (0.25 g) , 2-thenoyl chloride (0.14 ml) and triethylamine (0.18 ml) were reacted in the same manner as in Example 2 (a) and worked up to give the desired compound (0.32 ml). g, 87 7).

Specific rotation ([α] .2 ^< ): +8.8. (C = 1.00, EtOH); IR spectra (CHClav-. 'Cni- ¹ : 3287, 2936, 2815, 1630, 1602;

NM R spectrum _{(CDC 1 3) δ ppm:} .. 1 7 3 - 1 9 5 (2 H, m), 2. 0 5 (1 Η, t, J = 1 0. 6 Η ζ), 2. 3 3 (1 Η, dt, J = 3.2 Η ζ, J = 11.4 Η), 2.62 (2 Η, t, J = 6. Ο Η), 2. 6 7- 3.10 (6Η, m), 3.56 (2Η, q, J = 5.6Η), 3.80 (1Η, dt, J = 2.7 7, J = 1 1.6 Η)), 6.73 (1 Η, t, J = 7.3 Η), 6.75 (1,, brs), 6.8 2 (1 Η, d, J = 8 Ι Η)), 6. 9 8-7.14 (3 ,, m), 7.45-7.50 (2 Η, m

) ο

 (b) (+) 1 3-[2-(2-Tenylamino) ethyl] 1, 2.3.4, 4a, 5, 6-HexahiDraw 1 H-Virazino [1, 2-a] Quinoline 1 Hydrochloride

 (+) 3-[2 -— (2-tenolylamino) ethyl] -2.3,4,4a, 5,6-hexahi draw 1H-Virazino [1,2, a] quinoline (0.31 g) was reacted in the same manner as in Example 2 (b) and worked up to give the desired compound (0.34 g. quantitative).

Specific rotation ([α] *): + 2.3 ° (C = 1.01.EtOH); «Point: 1 85—190 X: (decomposition):

 IR spectrum (KBr) Vwcm- ': 3264, 2941, 2922, 25556, 1644, 1602;

 NMR spectrum (DMS 0—ds) δ ppm: 1.59-1.69 (1H, m), 1.90-2.05 (1H, m), 2.67 (1H, m) dt .J = 4.

5 Hz, J = 16.2 Hz), 2.81 (1H, ddd, J = 5.5 Hz, J = 10.9 Hz, J = 16.2 Hz) , 2.91 (1 H. Q, J = 10.3 H z)

, 3.00-3.20 (2 H, m), 3.20-3.60 (3 H, nd).

6 0-3.80 (4 H, m), 4.1 1 (1 H, d, J = 1 0.1 Hz), 6.70 (1 H, t, J = 7.3 Hz ), 6.91 (1 H, d, J = 8.3 Hz), 6.98 (1 H, d, J = 7.3 Hz), 7.06 (1 H. T, J = 8.3 Hz), 7.18 (1H, t, J = 4.3Hz), 7.79 (1H, d, J = 5.0Hz), 7.89 (1H , d, J = 3.4 Hz), 8.98 (1H, brs), 10.0.71 (1H, brs).

 Example 6 7

 (I) I 3— [2- (3-Tenylamino) ethyl] I 2.3,4,4a.5,6—Hexahi draw 1H—Virazino [1,2, a] quinoline monohydrochloride

 (Exemplary compound number: 1-343)

 (a) (-)-3-[2-(3-tenylamino) ethyl] 1, 2, 3, 4, 4 a.

 (1) 1—3— (2—aminoethyl) 1-2,3,4,4a, 5.6—Hexahydro 1H—Virazino [1,2, a] quinoline (0.26 g ), 3-thenoyl acid (0.15 g), getyl cyanophosphonate (0.18 ml) and triethylamine (0.32 ml) were reacted in the same manner as in Example 31 (a), and post-treated. As a result, the desired compound (0.23 g, 61%) was obtained.

 Specific rotation ([a] *): 8.7. (C = l. 05, E t 0 H);

IR spectrum (KBr) v .., cm— ¹ : 3285, 2936.2812, 1639, 1603; NM R Subeku Torr _{(CDC 1 3) δ ppm:} .... 1 7 5 - 1 94 (2 H, m) 2. 0 4 (1 H, t, J = 1 0. 6 H z) 2. 3 2 (1 H. Dt, J = 3.1 Hz, J = 1 1.4 Hz), 2.63 (2 H, t, J = 6.0 Hz), 2.69-3 3.57 (2H.q, J = 5.7Hz), 3.80 (1H, dt, J = 2.7Hz, J = 1 1 6 H z), 6.72 (1 H, t, J = 7.3 H z), 6-70 (1 H, brs), 6.8 1 (1 H, d, J = 8- 3 Hz), 7.00 (1 H, d, J = 7.3 Hz), 7.10 (1 H, t, J = 8.2 Hz), 7.32-7. 38 (2H, m), 7.86 (1H, dd, J = 1.3Hz, J = 3.2Hz) o

 (b) (—) 1—3— [2— (3-Tenylamino) ethyl] —1,2,3,4,4a, 5,6-hexahi draw 1H—Virazino [1,2—a] quinoline

(I) I 3— [2— (3-Tenylamino) ethyl] I, 2,3.4,4a.5,6-hexahidraw 1H-Virazino [1,2—a] quinoline (0.2 2g) was reacted in the same manner as in Example 31 (b) and worked up to give the desired compound (0.17 g, 71%).

Specific rotation ([na] ⁴ ): One 2.7. (C = l.04, Et0H); Melting point: 171-17-177;

IR spectacle (（Β Γ) ν · cm ” ¹ : 32,77,3058,2938,2584,166,0,163

NMR spectrum _{(DMS 0 - d e) δ} ppm:... 1 5 7 - 1 6 8 (1 H, m), 1 9 0 - 2. 0 5 (1 H, m), 2. 6 7 ( 1 H, dt, J = 4.

J = 16.1 Hz), 2.81 (1 H, ddd, J = 5.5 Hz, J = 10.9 Hz, J = 16.2 Hz) 2.91 (1H.q, J = 11.1.1Hz)

.3.00-3.20 (2H.m) .3.20-3.60 (3H, nd), 3.

6 0-3.80 (4H.m). 4.10 (1H.d, J = 11.2Hz), 6.

7 0 (1 H. T, J = 7.3 H z). 6.91 (1 H, d, J = 8.3 H z), 6.98 (1 H, d, J = 7. 3 H z), 7.06 (1 H .t.J = 8.3 H z ), 7.57 (1H, dd. J = 1.0 Hz, J = 5.0Hz) .7.61 (1H, dd, J = 3.0Hz, J = 4. 8Hz), 8.23 (1H, d, J = 1.9Hz), 8.76 (1H, brs), 10.0.51 (1H, brs).

 Example 68

 (+) 1-3-[2-(3-Tenylamino) ethyl] 1, 2, 3, 4.4 a, 5, 6-Hexahi draw 1 H-Virazino [1, 2-a] quinoline monohydrochloride

 (Exemplary Compound No .: 1-343)

 (a) (+) — 3— [2-(3—Tenylamino) ethyl] 1.2.3, 4, 4 a, 5, 6—Hexahydro 1 H-Virazino [1,2—a] N

 (+) 1-3-(2-aminoethyl) 1, 2,3,4,4a, 5,6-hexahydro 1H-birazino [1,2, a] quinoline (0.25 g ), 3-thenoyl acid (0.15 g), getyl cyanophosphonate (0.18 ml) and triethylamine (0.16 ml) were reacted in the same manner as in Example 31 (a). This gave the desired compound (0.27 g, 73%).

Specific rotation ([α] ^.ϊ4 ): ^+9.4 . (C = 1.00, EtOH);

IR spectrum (KBr) V cm— ¹ : 3287.2936, 2813, 1639.1603;

NM R spectrum _{(CDC 1 3) δ ppm:} 1. 76 - 1. 93 (. 2 H m), 2. 0 5 (1 H, t, J = 1 0. 6 H z), 2. 33 ( 1 H, dt, J = 3.2 Hz, J = 11.4 Hz), 2.64 (2H, t, J = 6.0 Hz). 2.68-3.07 ( 3.57 (2 H, q, J = 5.7 Hz). 3.80 (1 H. Dt, J = 2.7 Hz, J = 1 1.6 Hz) , 6.71 (1H, t, J = 7.3Hz), 6.76 (1H, brs), 6.81 (1H, d, J = 8.3Hz), 7.00 (1 H, d. J = 7.3 Hz). 7.10 (1 H, t, J = 8.3 Hz), 7.3 1-7.38 (2 H, m ), 7.86 (1H.dd.J = 1.3Hz.J = 3-2Hz).

(b) (+) 1-3-[2-(3-Tenylamino) ethyl] 1, 2.3.4.4 a, 5, 6-Hexahi draw 1 H-Virazino [1, 2-a] quinoline (+)-3-[2-(3-Tenylamino) ethyl] 1, 2, 3, 4, 4 a, 5, 6-Hexahi draw 1 H-Virazino [1.2-a] Quinoline (0. 26 g) was reacted in the same manner as in Example 31 (b), and worked up to give the target compound (0.1%).

29 g, quantitative).

Specific rotation ([α]; ^{ί <ι} ): + 2.5 ° (C = ^{1.00, EtOH} ); «Point ^174-178 ;

IR spectra (KBr) V cm— ¹ : 3281, 307, 294, 1, 254, 165, 1.1, 602;

 NMR spectrum (DMSO-ds) δ ppm: 1.59-1.69 (1H, m), 1.90-2.05 (1H, m), 2.67 (1H , dt, J = 4.

5 Hz, J = 16.0 Hz), 2.8 1 (1H, ddd, J = 5.5 Hz, J = 10.9 Hz, J = 16.2 Hz) , 2.9 1 (1 H, q, J = 1 1 .1 H z)

, 3.00-3.20 (2H.m), 3.20-3.60 (3H, nd), 3.

60-3.80 (4H.m), 4.11 (1H, d, J = 11.0Hz), 6.

70 (1 H, t, J = 7.3 Hz), 6.91 (1 H, d, J = 8.3 Hz), 6.98 (1 H. D, J = 7. 3Hz), 7.06 (1H, t.J = 8.3Hz), 7.57 (1H, dd, J = 1.0Hz.J = 5.0Hz) , 7.6 1 (1 H, dd, J = 3.0 Hz, J = 4.8 Hz), 8.24 (1 H, d, J = 1.9 Hz), 8.7 9 (1 H, brs), 10. 6 4 (1 H, brs).

 Example 6 9

 (I) I 3 — [4- (2-Virazinecarbonylamino) butyl] I 2,3,4.4a, 5,6-hexahidraw 1H-Virazino [1,2—a] quinoline Monohydrochloride (Exemplary compound number: 1 — 2 4 8)

 (a) (—) 1 3 — [4- (2-pyrazinecarbonylamino) butyl] 1, 2,3,4.4 a, 5.6—Hexahi Draw 1 H—Virazino [1,2-a〗 Kinoline

(1) 1-3-(4-aminobutyl) 1-2, 3.4, 4a.5, 6-hexahydrid Example 1 2H-Virazino [1,2—a] quinoline (0.47 g), 12-Virazinyl chloride (0.31 g) and triethylamine (0.30 mI) were used in Example 2. The target compound (0.55 g, 83%) was obtained by reacting in the same manner as in (a) and performing post-treatment.

Specific rotation ^{(. [Α] 2 *)} : - 9. 2 ° (C = 1. 0 2. E t OH);

IR spectrum (KBr) V cm " ¹ : 312, 2936, 2812, 1656, 1603;

NMR spectrum (CDCl ₃ ) 5 ppm: 1.55-2.00 (7H, m), 2.20 (1H, J = 3.2 Hz, J = 11.4) Hz), 2.42 (2H, t, J = 7.0Hz), 2.62-3.13 (6H, m), 3.54 (2H, q, J = 6. 3 Hz), 3.76 (1 H, dt, J = 2.6 Hz, J = 11.8 Hz), 6.70 (1 H, t, J = 7.3 Hz 6.79 (1H, d.J = 8.1Hz), 6.98 (1H, d, J = 7.3Hz), 7.06 (1H, t.J = 8.1 Hz), 7.99 (1H, brs), 8.50 (1H, dd.J = 1.5 Hz, J = 2.4 Hz), 8.74 (1H, d, J = 2.4 Hz), 9.41 (1 H, d, J = 1.5 Hz).

 (b) (—) 1 3— [4- (2-Virazinecarbonylamino) butyl] 1 2, 3.4.4 a, 5, 6-Hexahi Draw 1 H-Virazino [1.2-a ] Quinoline monohydrochloride

 (1-)-3- (4- (2-Virazinecarbonylamino) butyl) 1,2,3,4,4a, 5,6-hexahydro-1H-birazino [1,2-a] quino The target compound (0.48 g, quantitative) was obtained by reacting phosphorus (0.44 g) in the same manner as in Example 2 (b) and performing post-treatment.

Specific rotation ([alpha] ^26.): One 9. 8 ° (. C = l 0 2, E t 0 H); tt point 1 9 0 1 94 (decomposition):

IR spectrum (KBr) ν · ”cm- ¹ : 336 5.2 29 28. 2591, 1664.1603;

NMR Spectra (DM SO—ds) 5 ppm: 1.5 6-1.68 (3 1.70-1.83 (2H.m), 1.9 1-2.00 (1H, m), 2.66 (1H, dt, J = 4 J = 16.1 Hz), 2.75-2.86 (2H, m) .3.00-3.20 (4H, m), 3.2 0-3.45 (3H, nd), 3.45-3.65 (2H.m), 4.07 (1H, d, J = 10.7 Hz), 6 6 9 (1 H, t, J = 7.3 Hz), 6.90 (1 H, d, J = 8.1 Hz), 6.97 (1 H, d, J = 7 3 H z), 7.06 (1 H. T, J = 8.1 Hz), 8.74 (1 H, t, J = 1.8 Hz), 8.88 (1 H, d, J = 2.3 Hz), 9.04 (1 H, t, J = 6.0 Hz) .9.20 (1 H, d, J = 1.4 Hz) 10. 6 3 (1 H, brs).

 Example 7 0

 (+) — 3 — [4- (2-pyrazinecarbonylamino) butyl] 1, 2,3,4,4a, 5,6-hexahi draw 1 H-Virazino [1,2—a] quinoline Monohydrochloride (Exemplary compound number: 1 2 4 8)

 (a) (+) — 3 — [4- (2-Virazinecarbonylamino) butyl] 1,2,3,4,4a, 5,6-Hexahi draw 1 H-Virazino [1,2—a Quinoline

 (+) — 3 — (4-Aminobutyl) 1, 2,3,4,4a, 5,6—Hexahydro 1 H—Virazino [1,2—a] quinoline (0.13 g ), 2-chlorinated virazine (0.08 g) and triethylamine (0.08 ml) were reacted in the same manner as in Example 2 (a), followed by post-treatment to obtain the desired compound (0.1). 6 g, 86%).

Specific rotation ^{([α] 24.):} . + 9. 3 ° (. C = l 0 4, E t 0 H); IR spectrum (KB r) ν ·, c m '1: 3 3 1 6, 2936, 2812, 1656, 1602;

NMR spectrum _{(CDC 1 3) δ ppm:} .... 1 5 5 - 2 0 0 (7 H, m), 2 2 0 (1 Η, J = 3. 2 Η ζ, J = 1 1 4 Η ζ), 2.4 1 (2 Η, t, J = 7 Η Η Η), 2.60-3.1 2 (6,, m) .3.5 4 (2 q, q, J = 6.3 ζ), 3.75 (1,, dt, J = 2.6 Η ζ. J = 1 1.8 H z), 6.70 (1 H, t, J = 7.3 H z). 6.79 (1 H, d, J = 8.1 H z), 6.99 (1 H, d, J = 7.3 Hz), 7.07 (1H, t, J = 8.1 Hz). 7.98 (1H, brs), 8.50 (1 H, dd , J = 1.5 Hz, J = 2.4 Hz), 8.75 (1H.d, J = 2.4 Hz), 9.42 (lH, d, J = 1 5 Hz).

 (b) (+)-3-[4-(2-virazinecarbonylamino) butyl] 1, 2, 3, 4, 4 a, 5, 6-hexahi draw 1 H-virazino [1, 2-a ] Quinoline monohydrochloride

 (+)-3-[4-(2-pyrazinecarbonylamino) butyl] 1, 2, 3, 4.4 a, 5, 6-hexahydro 1 H-virazino [1, 2-a] quinoline (0.11 g) was reacted in the same manner as in Example 2 (b) and worked up to obtain the desired compound (0.12 g, quantitative).

Specific rotation ^{_{([a] D 26):}} + 9. 3 ° (C = 0. 9 9, E t 0 H); mp: 1 9 0-; I 94 (decomposed);

IR spectrum (Κ Β Γ) ν ···, cm " ¹ : 33 98.2 9924, 2590, 1663, 1604;

NM R spectrum _{(DMS 0- d e) δ ppm} :..... 1 5 7 - 1 6 8 (3 H, m), 1 7 0 - 1 8 3 (2 H, m), 1 9 1 -2.00 (1H, m), 2.66 (1H.dt.J = 4.6Hz, J = 16.2Hz), 2.75-2.2.86 ( 2H, m), 3.00-3.20 (4H, m), 3.20-3.45 (3H, nd), 3.45-3.65 (2H , m), 4.07 (1 H, d. J = 11.4 Hz) .6.69 (1 H, t, J = 7.3 Hz), 6.90 (1 H d, J = 8.1 Hz), 6.98 (1H, d. J = 7.3 Hz), 7.06 (1H. t, J = 8.1 Hz). 8.74 (1H, t.J = 1.8 Hz) .8.88 (1H.d.J = 2.3Hz), 9.04 (1H, t, J = 6) 0 H z), 9.20 (1 H, d, J = 1.4 H z), 10.0.7 (1 H. Brs). Reference example 1

 3- (4-aminobutyl) 1-2,3,4.4a, 5.6-hexahydro 1H-birazino [1,2-a] quinoline

 3-((4-phthalimidobutyl))-1,2,3,4,4a, 5,6-hexahydro-1H-virazino [1.2-a] quinoline (0.8 g) was added to ethanol (0.8 g). 20%), 80% hydrazine hydrate (2501) was added, and the mixture was heated under reflux for 15.5 hours. The solvent was distilled off under reduced pressure, and a saturated aqueous sodium hydrogen carbonate solution was added to the obtained residue, followed by extraction with methylene chloride. The organic layer was washed with a saturated aqueous sodium carbonate solution. After drying over anhydrous sodium rutherate, the solvent was distilled off under reduced pressure to obtain the desired compound (0.49 g, 9296) as an oily substance.

NMR spectrum _{(CDC 1 3) δ ppm:} .... 1 4 - 1 7 (4 H, η d), 1 7 - 2. 0 (2 Η, m), 1 9 0 (1 Η, t, J = 1 1 Η ζ), 2.18 (1 Η, dt, J = 1 1 Η ζ, J = 3 Η ζ), 2.38 (2 Η, t, J = 7Hz), 2 6 5-3.1 (6Η, m), 2.73 (2Η, t, J = 7 =), 3.76 (1ζ, d, J = 1 22), 6 6 9 (1 Η, t, J = 7 Η), 6.80 (1 Η, d, J = 8 Η). 6.98 (1 Η, d, J = 7 ζ), 7.09 (1 Η, t, J = 8 Η ζ) „

 Reference example 2

 3- (3-aminobutyral pill) 1,2,3,4,4a, 5,6-Hexahi draw 1H-Virazino [1,2—a] quinoline

 3- (3-phthalimidoprovir) 1-2,3.4.4a.5,6-hexahydrol 1H-virazino [1,2—a] quinoline (426 mg), 80 % Hydrazine hydrate (107 µ1) was reacted in the same manner as in Reference Example 1 and worked up to give the target compound (209 mg, 75%) as a yellow oily substance.

NMR spectrum _{(CDC 1 3) δ ppm:} ... 1 6 - 1 9 5 (4 H, m), 1 9 0 (1 Η, t, J = 1 1 Η ζ), 2. 1 8 (1 Dt, J = 11 Η, J = 3 Η). 2.44 (2, t, J = 7 Η). 2.65-3.1 (6 Η, m). 2 7 8 (2,, t. J = 7 Η). 3.76 (1 Η, dt. J = 1) 2 H z, J = 3 H z), 6.69 (1 H, t, J = 7 H z), 6.79 (1 H, d, J = 8 H z), 6.98 (1 H d, J = 7 Hz), 7.08 (1H, t, J = 8 Hz).

 Reference example 3

 To 3- (2-aminoethyl) -1,2,3,4,4a, 5.6- Sahi draw 1H-birazino [1,2-a] quinoline

 3- (2-phthalimidoethyl) 1-2,3.4,4a, 5,6-hexahydro-1H-birazino [1,2-a] quinoline (0.53 g) and 80% Drazine hydrate (180xl) was reacted in the same manner as in Reference Example 1 and worked up to give the desired compound (0.28 g, 83%) as an oil.

NMR Subeku torr _{(CDC 1 3) 6 ppm:} ... 1 65 - 2. 0 (2 H, m), 1. 96 (1 Η, t, J = 1 1 Η ζ) 2. 24 (1 Η dt , J = 1 1Η, J = 3Η ζ), 2.45 (2Η, t, J = 6Η ζ), 2.65-2.75 (1Η, m), 2.75-3 1 (5Η, m), 2.83 (2Η, t, J = 6Η), 3.75 (1Η, d, J = 1 22), 6.69 (1Η, t, J = 7 Η ζ), 6.80 (1 d, d, J = 8 Η ζ), 6.98 (1 Η. d. J = 7 Η ζ), 7.09 (1,, t, J = 8 ζ ζ).

 Reference example 4

 3- (4-bromobutyl) -1-5.5-dimethylthiazolidine-1,2,4-dione 5,5-dimethylthiazolidine-12,4-dione (1.5 g) and 1.4-dibromobutane (10.8 g) ) Was dissolved in DMF (30 ml), 55% oily sodium hydride (450 mg) was added little by little under ice-cooling and stirring, and the mixture was stirred at room temperature for 4 hours. The reaction mixture was poured into a saline solution, extracted with ethyl acetate, and the extract was washed with water and dried with anhydrous sodium sulfate. The residue obtained by evaporating the solvent under reduced pressure was purified using silica gel column chromatography (eluent; hexane, then hexane: ethyl acetate = 4: 1) to obtain the desired compound (1.89 g). . 65%) as an oily substance,

NM R spectrum _{(CDC 1 3) δ ppm:} . 1. 7 - 1. 95 (4 H m ), 1.71 (6H.s) .3.42 (2H, t, J = 7Hz), 3.65 (2H, t, J = 7Hz);

IR spectrum (CH Cl ₃ ) v „ _Jt cm- ': 1 748, 1 683, Reference example 5

 3- (4-bromobutyl) -1-5-isoprovirthiazolidine-1.2.4-dione 5-isobromovirthiazolidine-1,4-dione (0.57 g), 1,4-dibromobutane (3.9 g) and 55 % Oil-based sodium violet (160 mg) was reacted in the same manner as in Reference Example 4 and worked up to give the desired compound (740 mg, 70%) as an oil.

NMR spectrum _{(CDC 1 3) δ ppm:} 0. 95 (. 3 H d, J = 7 H z), 1. 07 (3 H, d, J = 7 H z), 1. 7 - 1. 95 (4 H, m), 2.55-2.7 (1 H, m), 3.42 ((2 H, t, J = 7 Hz), 3.6

J (7Hz). 4.26 (1H, d, J = 4Hz);

IR spectrum Honoré _{(CH C l 3) v,} "cm- 1: 1 749, 1 683.

 Reference example 6

 4-funylcarbamoylbutyl bromide

 Aniline (2.28 ml) and triethylamine (3.84 ml) were dissolved in tetrahydrofuran (100 ml), and the mixture was stirred under ice-cooling with stirring for 5-bromovaleryl chloride (100 ml).

5.00 g) was added dropwise, and the mixture was stirred at room temperature for 2 hours. After the precipitated crystals were removed by tt, the solvent was distilled off under reduced pressure, the obtained residue was made to be ethyl acetate, washed with water, and organic B was dried using anhydrous magnesium phosphate. The solvent was distilled off under reduced pressure, and the resulting residue was subjected to silica gel column chromatography (eluent; hexane: ethyl acetate-3).

: 1) to obtain the desired compound (5.95 g, 93%).

 R f value: 0.5 (Developing agent: hexane: ethyl thiocyanate = 3: 1);

NMR spectrum _{(C DC 1 3) 6 ppm} :.. 1. 8- 2. 0 (4 H, m) 2. 39 (2 H, t, J = 6. 6 Η ζ J = 7. 3 Η ζ ), 3.42 (2 Η. T, J = 6.6 Η, J = 5.9 Η), 7.10 (1 Η. T. J = 7.3 Η), 7.26 -7.34 (2nd, m), 7.43 (1st.br.s), 7.51 (2 H, d, J = 7.9 Hz)

 Reference Example 7

 (1) 1,2,3,4,4a, 5,6—Hexahi Draw 1 H—Virazino [1,2,1a] quinoline

 (a) (+) — 2 — [N— (1-phenylethyl) force lvamoyl] 1-1.2, 3, 4—Tetrahydroquinoline and (1) 1 2 — [N— (1-phenylethyl) force Lubamoyl] 1, 1, 2, 3, 4 te Trahidrokinoline

 1,2,3,4-Tetrahydroquinoline-l-hydroxycarboxylic acid (30.7 g), (

5) Dissolve phenylethylamine (24.3 ml) and triethylamine (26.4 ml) in methylene chloride (150 ml) under a nitrogen atmosphere. Then, gentyl cyanophosphonate (28.9 ml) was added, and the mixture was kept at room temperature for 14 hours. The reaction solution was washed with a saturated saline solution and then dried using anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography to obtain (+)-2- [N- (1-phenylethyl) -capsulebamoyl] 1-1,2,3,4-te Droquinoline (18.2 g, 37%) and (1) -12- [N- (1-phenylethyl) tylrubamoyl] 1-1,2,3.4-tetrahydroquinoline (19.2 g) 3 g, 40%).

 (+) — 2 — [N— (1-phenyleneethyl) rubamoyl] 1, 1, 2, 3.4 テ Physical data of traffic hydroquinoline

Specific rotation ^{(. [Α] 22):} + 80. 6 ° (. C = 1 0 0, CHC 1 3);

IR spectrum _{(CHC 1 3) ν, ·} , c m- 1: 3 3 8 9, 2 9 34, 1

6 6 4, 16 08;

NMR spectrum _{(CDC 1 3) δ ppm:} . (. 3 H, d, J = 7 Ο Η ζ)... 1 48, 1 8 5 - 1 9 7 (1 Η, m) 2. 2 2 - 2.33 (1 Η, m), 2.42-2.53 (1 ,, m), 2.63-2.74 (1 Η, m), 3.95-4. 25 (2 Η, m) .5.08-5.20 (1 ,, m), 6.66 (1 ,, d, J = 7.9 Η), 6.73 (1 Η, t, J = 7.2 7.), 6.97-7.08 (3 Η.m), 7.13-7.35 (5 ,, m). (1)-2-[N— (1-phenylethyl) rubamoyl] 1, 2.3, 4 -tete Physical data of traffic hydroquinoline

Specific rotation (. ^{[Α] 2 <): - 3} 0. 0 ° (. C = 1 0 0, CHC 1 3);

IR spectrum _{(CHC l 3) v -,} c m- ':. 2 9 8 0, 2 94 3, 2

8 5 7, 1 6 8 3;

NMR spectrum _{(CDC 1 3) δ ppm:} .. 1 44 (. 3 H, d, J = 6 9 H z), 1 8 5 - 2. 0 0 (1 H, m), 2. 3 1 - 2.42 (1H, m), 2.53-2.66 (1H, m), 2.73-2.82 (1H, m), 3.98 (1H, m) q, J = 5.0 Hz), 4.10 (1H, brs), 5.12-5.23 (1H, m), 6.60 (1H, d, J = 7.9 Hz), 6.73 (1H, t, J = 7.3Hz), 6.99-7.07 (3H.m), 7.25-7.3 7 (5H, m).

 (b) (—) 1 2 — [N— (1-phenylethyl) aminomethyl] 1 1,2,3.4-tetrahydrodroquinoline

 (+) — 2— [N— (1-phenylethyl) kylarvamoyl] obtained in Reference Example 7 (a), 1,1,2,3,4-tetrahydroquinoline (10.77 g) It was dissolved in anhydrous tetrahydrofuran (150 ml), borane-methylsulfide complex (10. OM, 30 ml) was added dropwise under a nitrogen atmosphere and ice-cold stirring, and the mixture was stirred at room temperature for 3 days. . 6N hydrochloric acid was added to inactivate the excess borane-methyl sulfide complex, then neutralized using a saturated aqueous sodium bicarbonate solution, extracted with ethyl acetate, and the organic β was extracted with saturated saline. And dried using anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain the target compound (8.95 g, 88%) as a colorless oily substance.

Specific rotation ([α]: -. 54. 4 ° (C = 0. 9 9, E t 0 H); IR spectrum _{(CHC 1 3) ν, ·} , cm "1: 34 0 8, 2 9 63.2

9 32, 2 84 6.16 05, 15 84;

NMR spectrum _{(CDC 1 3) 5 ppm:} ..... 1 3 7 (. 3 H, d, J = 6 6 H z) 1 4 5 - 1 6 0 (1 H, m) 1, 8 0 -1.8 9 (1 H, m ), 2.39 (1H.dd.J = 9.2Hz.J = 11.7Hz), 2.63-2.87 (3H, m), 3.25-3 35 (1 H, m), 3.79 (1 H, q, J = 6.6 Hz), 4.30-4.53 (1 H, brs), 6.50 (1 H, d , J = 7.9 Hz), 6.57 (1H, t, J = 7.3 Hz), 6.91-6.99 (2H, m), 7.19-7. 37 (5H, m).

 (c) (1) 1 2-[N-(1-phenylethyl) 1 N '-tert-carbonyl carbonylaminomethyl] 1, 1, 2, 3, 4-tetrahydroquinoline obtained in Reference Example 7 (b). (1-)-2- [N- (1-1-fuunylethyl) aminomethyl] -11,2,3,4-tetrahydroquinoline (8.75 g) was dissolved in dioxane (100 ml). At room temperature, tert-butyl butyl carbonate (8.5 ml) was added dropwise under stirring, and the mixture was stirred at room temperature for 2 hours. After the reaction solution was poured into water, the mixture was extracted with ethyl ethyl ether, and the organic layer was washed with saturated saline and dried using anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography to obtain the desired compound (9.01 g, 75%) as a colorless oily substance.

Specific rotation ([α] ⁴ ): — 83.3 ° (C = 3.42, Et0H);

IR spectrum _{(CHC 1 3) τ ··,} cm- 1: 2 980, 2 936, 1 6 8 1, 1 6 05;

NM R spectrum Honoré _{(CDC 1 3) δ ppm:} 1. 35 - 1. 60 (2 H, m), 1. 47 (9 Η, s), 1. 52 (3 Η, d, J = 8 5 5), 2.5 3-2.63 (2 ,, m) .2 · 95-3.15 (2,, m). 3.15-3.30 (1 Η, m ), 4.00-4.40 (1 Η.brs), 5.25-5.55 (1 ,, m), 6.42 (1 Η.d, J = 7.9 ζ), 6.56 (1 ,, t, J = 7.5 Η). 6.87-6.96 (2 ,, m). 7.14-7.36 (5 ,, m).

 (d) (1) 1-3-(1-phenylethyl) 1-2.3, 4, 4 a. 5, 6-Hexahi draw 1-oxovirazino [1, 2-a] quinoline

(1) 1 2— ΓΝ— (1 1 phenylethyl) 1 N '— Yuichi Sharib Toxica Ruponylaminomethyl] 1.1.2.3.4-Tetrahydroquinoline (9.0 g) is dissolved in tetrahydrofuran (90 ml), and the mixture of bipyridine (90 ml) is stirred under ice-cooling and stirring in a nitrogen atmosphere. 3. O ml) and chloroacetyl chloride (2.2 ml) were added dropwise, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was poured into ice water, extracted with ethyl acetate, the organic layer was washed with saturated saline, and dried using anhydrous magnesium triluate. The solvent was distilled off under reduced pressure, and the obtained residue was dissolved in tetrahydrofuran (40 ml), and trifluoroacetic acid (50 ml) was added under a nitrogen atmosphere, followed by stirring at room temperature for 1 hour. The solvent was distilled off under reduced pressure, the obtained residue was dissolved in dimethylformamide (50 ml), potassium carbonate (5.6 g) was added, and the mixture was stirred at 50 for 1 hour. The reaction solution was poured into ice water, extracted with ethyl acetate, the organic layer was washed with saturated saline, and dried using anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography to obtain the desired compound (6.08 g, 81%) as a colorless powder.

Specific rotation ^{(. [Α] 2 <)} : - 1. 88 ° (C = 2. 1 8, E t OH); IR spectrum _{(CHC l 3) i ,, x} cm- 1: 2 980, 2809 , 1650;

NM R spectrum _{(CDC 1 3) δ ppm:} 1. 4 1 (3 H, d, J = 6 - 6 H z), 1. 8 1 - 1. 9 1 (l H, m), 2. 07 -2.23 (1H, m), 2.54 (1H.dd, J = 6.1Hz, J = 11.8Hz), 2.79-

2.97 (3H, m), 3.26-3.45 (2H.m), 3.42 (1H, q.J = 6.6Hz), 3.55-3. 64 (1 H .m), 7.03-7.2 0 (

3H, m), 7.22-7.39 (5H, m). 7.92 (1H, d, J = 7.8Hz).

 (e) (1) 1-3-(1-phenylethyl) 1-2, 3, 4, 4 a. 5.6-Hexahi draw 1 H-Virazino [1, 2-a] quinoline

Reference example 7 (d) obtained from (d) (1-)-3- (1-phenylethyl) -12,3.4.4a, 5,6-hexahi draw 1-oxovirazino [1,2-a] quinolin (6.0 g) was dissolved in anhydrous tetrahydrofuran (180 ml), and the mixture was dissolved in a nitrogen atmosphere. Then, borane-methyl sulfide complex (10. OM, 20 m 1) was added dropwise under ice-cooling and stirring with H, and the mixture was stirred at room temperature for 4 days. After completion of the reaction, excess borane-methyl sulfide complex is deactivated using 6N hydrochloric acid, the pH of the solution is made alkaline using a saturated aqueous sodium hydrogen carbonate solution, and then extracted with ethyl acetate. The layer was washed with a saturated saline solution and dried using anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography to obtain the target compound (4.53 g, 79%) as a colorless powder. ^{. [α] 4): -} 33. 9 ° (C = l 32, E t OH); IR spectrum _{(CHC l 3) v_ ,, cm-} ': 2 977. 2 93 6, 2 8 2 2, 1 6 0 2;

NMR spectrum _{(CDC l 3) 5 p pm} :. 1. 39 (. 3 H, d, J = 6 7 H z), 1 69 - 2. 00 (3 H, m), 2. 1 0 (1 H, dt, J = 3-1 H z, J = 10.9 H z), 2.65-2.95 (4 H, m), 3.02-3.12 (2 H, m ), 3.37 (1H, q, J = 6.7Hz), 3.61-3.67 (1H, m), 6.67 (1H, t, J = 7.3H z), 6.73 (1 H. d. J = 8.3 H z), 6.97 (1 H, d, J = 7.3 H z), 7.05 (1 H, t, J = 8.3 Hz), 7.21-7.39 (5H, m).

 (f) (-)-2, 3, 4, 4 a, 5, 6—hexahydro 1 Η-birazino

 [1,2—a] quinoline

Reference Example 7 (e) 1-3- (1-1-phenylethyl) 1-2,3,4,4a, 5.6-hexahidro 1H-birazino [1.2-a] quino obtained in (e) Phosphorus (4.48 g) is dissolved in methanol (75 ml) and 10% palladium-single charcoal purple (4.5 g) and ammonium formate (4.8 g) at room temperature under a nitrogen atmosphere. Then, the mixture was heated under reflux for 1 hour. After removing the catalyst, the solvent was distilled off under reduced pressure. Saturated saline was added to the obtained residue, and the mixture was extracted with dichloromethane, and the organic layer was dried using anhydrous magnesium triluate. The solvent was distilled off under reduced pressure to obtain the target compound (2.25ε, 78%) as an oil R. Specific rotation ^{([α] 2 *.)} : -! 2 0. 3 ° (C = 0. 97, E t OH): IR spectrum _{(CHC 1 3) / ,,, cm-} ': 2 948, 2 839, 1 6 0 3:

NM R spectrum _{(CDC 1 3) 6 ppm:} 1. 49 - 1. 99 (. 3 H m), 2. 58 - 3. 1 5 (8 H, m), 3. 75 (1 H, dt, J = 2.5 Hz, J = 1 1.8 Hz), 6.70 (1H, t, J = 7.2Hz), 6.79 (1H, d, J = 8. 2Hz), 6.98 (1H, d, J = 7.2Hz) .7.08 (1H, t.J = 8.2Hz) o

 Reference Example 8

 (+) 1,2,3,4,4a, 5,6-Hexahi draw 1 H-Virazino [1,21a] quinoline

 (a) (+) 1 2-[N-(1-phenylethyl) aminomethyl] 1, 1, 2, 3, 4-tetrahydroquinoline

 Reference Example 7 (b) was obtained using Reference Example 7 (b) obtained from (1) 1 2— [N— (1-Phenylethyl) potassium rubamoyl] obtained in Reference Example 7 (a), 1, 2, 3, 3, 4-tetrahydroquinoline. The reaction was carried out in the same manner as in the above), and post-treatment was performed to obtain the desired compound (7.1 g, 83%).

Specific rotation ([α] » ²⁴ ): +29.8. (C = 1.00, EtOH);

IR spectrum (KBr) Vcm— ¹ : 3413, 3395, 2958, 2925, 2842, 1604.1583;

 NMR spectrum (CDC la) δ ppm: 1.38 (3H, d, J = 6.6 Hz). 1.49-1.66 (lH, m), 1.80- 1. 90 (1H, m), 2.44-2.84 (4H, m), 3.16-3.25 (1H, m), 3.75 (1H, q, J = 6 .6Hz), 4.42 (1H, brs), 6.50 (1H, d, J = 7.9Hz) .6.58 (1H.t, J = 7.2H) z), 6.91-6.9 (2H.m), 7.21-7.37 (5H, m).

(b) (1) 1-2-[N-(1-phenylethyl)-N '-tert-carbonylcarbonylaminomethyl] 1-1.2, 3, 4-Tetrahydroquinoline Reference Example 8 (+)-2-[N- (1-phenylethyl) aminomethyl] 1-1.2,3.4-tetrahydroquinoline (6.O lg) obtained in (a) was used in Reference Example 7 ( The target compound (7.2 g, 87%) was obtained by carrying out the reaction and the post-treatment in the same manner as in c).

Specific rotation ([<∑] ⁵ ): 15.8 ° (C = 1.00, EtOH);

IR spectrum _{(CHC 1 3) ν, ·} , cm ": 33 8 1, 2 974, 2 9 2 8. 2 85 1, 1 689, 1 607;

NM R spectrum Honoré _{(CDC 1 3) δ ppm:} .. 1. 24- 1. 72 (2 H, m), 1 46 (9 Η, s), 1. 5 3 (3 Η, d J = 8.5 Η ζ), 1.7 8—1 · 88 (1 Η, m), 2.60-2.82 (2 Η, m), 2.95-3.45 (3 Η, m) , 5.30-5.65 (1 st, brs). 6.00-6.2

5 (1Η, m), 6.54 (1Η, t, J = 7.5Η), 6.86-6.93 (2Η, m), 7.16-7.46 (5 Η, m).

 (c) (+) — 3— (1-phenylethyl) 1 2, 3, 4, 4 a, 5.6— Hexahi draw 1 1-oxovirazino [1, 2-a] quinoline

 (1) 12- [N- (1-phenylethyl) -1-N'-tert-butyloxycarbonylaminomethyl] 1-1,2,3.4-tetrahydroquinoline (5) obtained in Reference Example 8 (b) .40 g) was reacted in the same manner as in Reference Example 7 (d) and worked up to give the desired compound (3.86 g. 86%).

Specific rotation ^{_{([a] D 2S):}} + 2 0. 3 ° (C = 1. 00. E t OH);

IR spectrum (CHCl ₃ ) v, cm— ¹ : 3602, 2979, 2937, 2900.1.650;

NM R spectrum Honoré _{(CDC 1 3) δ ppm 1.} 4 3 (3 H d, J = 6 7 H z..), 1 82 -.. 1 9 1 (2 H, m) 2. 3 1 (1 H, dd, J = 8.6 H z. J = 12.0 H z). 2.81-302 (3 H, m). 3.10 (1 H. D. J = 16.5 Hz), 3.43 (1 H, q, J = 6.7 Hz), 3.

6 3-3.73 (1 H, m), 3.77 (1 H, d d, J = 2.4 Hz, J = 1

6.5 Hz). 7.0 2-7.2 1 (3 H .m), 7.25-50 (5 H, m). 8.02 (1 H. d. J = 8.4 Hz).

 (d) (1) 1-3-(1-phenylethyl) 1-2,3,4.4 a, 5, 6-hexahydro 1 H-virazino [1,2-a] quinoline

 Reference Example 8 (+) — 3— (1-phenylethyl) obtained in (c) 1. 2.3.4, 4a, 5, 6—hexahydro-1 1-oxovirazino [1.2—a] quinoline (4.77 g) was reacted in the same manner as in Reference Example 7 (e) and worked up to give the desired compound (4.02 g, 88%).

 Specific rotation ([α] *): 10.6 ° (C = 1.00, EtOH);

IR spectrum (CHC ₃ ) V cm " ¹ : 2978, 2937, 2820, 1732, 1602;

NMR spectrum _{(CD C 1 3) δ ppm} 1. 39 (3 H, d, J = 6 - 7 H z), 1. 57 - 1. 86 (3 H, m) 2. 24 (1 H, dt , J = 3.1 Hz, J = 11.3 Hz), 2.59-299 (5H, m), 3.14-3.30 (1H, m), 3.36 ( 1 H, q, J = 6.7 Hz), 3.79 (1 H, dt, J = 2.8 Hz, J = 11.8 Hz), 6.67 (1 H, t, J = 7-2 Hz), 6-79 (1 H, d, J = 8.2 Hz), 6.95 (1 H, d, J = 7.2 Hz), 7.07 (1 H, t, J = 8.2 Hz) .7.22-7.39 (5H, m).

 (e) (+)-2,3,4,4a, 5,6-Hexahydro-1H-virazino

 [1,2—a] quinoline

 Reference Example 8 (d) obtained in (d) 1 3— (1-phenylethyl) 1,2,3,4

, 4a, 5,6-Hexahi draw 1 H—Virazino [1,2—a] quinoline (4.

30 g), 10% palladium on charcoal purple (4.30 g) and ammonium formate (4.

60 g) was reacted in the same manner as in Reference Example 7 (f) and worked up to give the desired compound (2.18 g. 79%).

Optical rotation _{([a] D "):} + 22. 0. (C = 1. 00. E t 0 H); IR spectrum _{(CHC l 3) i _ ,,} cm- 1: 2950, 2842. 1 6

05; NM R spectrum _{(CDC 1 3) δ ppm:} . 1. 45 - 1. 9 9 (3 H, m) 2. 5 8 - 3. 1 6 (8 H, m), 3. 7 5 (1 H J = 2.5 Hz, J = 11.7 Hz), 6.69 (1 H, t, J = 7.3 Hz), 6.79 (1 H, d, J = 6.98 (1 H, d, J = 7.3 Hz), 7.08 (1 H, t, J = 8.2 Hz),

 Reference Example 9

 (1) 1-3 (4-aminobutyl) 1,2,3,4,4a, 5,6-hexahydro 1 H—Virazino [1,2—a] quinoline

 (I) I 3-(4-I-phthalimidobutyl)-2,3,4,4a, 5,6-Hexahi draw 1H-Virazino [1,2, a] quinoline (1.20 g ) And 80% hydrazine hydrate (0.37 ml) were reacted in the same manner as in Reference Example 1 and worked up to give the desired compound (0.66 g, 83%).

Specific rotation ^{(. [Α] 2 *)} : - 1 0. 3 ° (C = 0. 99, E t 0 H);

IR spectrum _{(CHC 1 3) ι ··,} cm- 1: 2 94 1, 2 849, 28 2 4, 1 6 02;

NM R spectrum _{(CDC 1 3) δ ppm:} . 1. 40 - 1. 66 (6 H, η d), 1 66 - 1. 94 (2 Η, m), 1. 90 (1 Η, t, J = 1 0.9 Hz), 2.18 (1 dt. Dt, J = 3.3 Η ζ, J = 11.4 Η), 2.38 (2 Η, t, J = 7.4 Η), 2.65-3.10 (6 ,, m), 2.73 (2 Η.t, J = 6.6 Η), 3.75 (1 ,, d , J = 1 2.Ο Η), 6.68 (1 Η, t, J = 7.2 Η), 6.79 (1 7, d, J = 8.2 Η), 6. 98 (1 Η, d, J = 7.2 ζ) 7 · 08 (1 Η, J = 8.2 H 2)

 Reference example 10

 (+) 1-3-(4-Aminobutyl) 1-23, 4, 4 a, 5, 6-Hexahydro 1 H-Virazino [1,2-a] Quinoline

(+) — 3— (4-phthalimidobutyl) 1 2.3.4.4 a, 5,6—hexahi draw 1 H-birazino [1.2-a] quinoline (1.20 g) and 80% Drazine hydrate (0.45 ml) was reacted in the same manner as in Reference Example 1 and worked up to give the desired compound (0.71 g, 89%).

Specific rotation ([α] *): + 1 0. 2 ° (. C = 1 0 0. E t OH); IR spectrum _{(CHC l 3) v ",,} c m- 1: 2 9 4 1 , 2 84 9, 2 8

23, 1602;

NM R spectrum _{(CDC 1 3) δ ppm:} ...... 1 4 0 - 1 6 6 (6 H, η d), 1 6 6 - 1 9 5 (2 Η, m) 1 9 0 ( 1 Η, t, J = 10.9 Hz), 2.19 (1 Η, dt. J = 3.3 Η, J = 11.4 Η), 2.38 (2 Η , t, J = 7.4 Η ζ), 2.65-3.10 (6 Η, m), 2.73 (2 Η, t, J = 6.6 ζ Η), 3.7 5 (1Η, d, J = 12.0 0), 6.6.7 (1Η, t.J = 7.2 2), 6.78 (1Η, d, J = 8. 2 Η), 6.98 (1 Η. D, J = 7.2 Η), 7.07 (1 Η, t, J = 8.2 Η)

 Reference example 1 1

 (1-) 1-3- (2-aminoethyl) -1-2.3, 4.4a, 5, 6-hexahydrol 1H-birazino [1.2-a] quinoline

 (I) -3-(2-phthalimidethyl) I 2,3,4,4a, 5,6-hexahi draw 1H-Virazino [1,2, a] quinoline (0.88 g ) And 80% hydrazine hydrate (0.31 ml) were reacted in the same manner as in Reference Example 1 and worked up to give the desired compound (0.54 g, 96%).

Specific rotation ^{([a] r> 2 <} ): - 1 1 6 ° (C = 1 2 9, E t OH.); IR spectrum (CHC la) / -, ' cm 1:.! 2 94 5 , 2 8 2 3. 1 6 0 2;

. NMR spectrum _{(CDC 1 3) δ ppm:} ... 1 4 9 (. 2 H brs), 1 6 8 - 1 9 9 (2 H, m), 1 9 5 (1 H, t, J = 10.6 Hz), 2.23 (1 H.dt, J = 3.2 Hz.J = 11.4 Hz), 2.44 (2H, t, J = 6.1 Hz), 2.65-2.75 (1H, m) .2.75-3.10 (5H.m), 2.82 (2H, t.J = 6. 1 H z), 3.74 (1 H, d 52

, J = 11.8 Hz), 6.69 (1H.t.J = 7.3 Hz), 6.79 (1H, d.J = 8.2 Hz), 6. 98 (1 H, d, J = 7.3 Hz), 7.08 (1 H, t, J = 8.2 Hz).

 Reference example 1 2

 (+) 1-3-(2-aminoethyl) 1, 2, 3, 4, 4 a5, 6-hexahydro 1 H-virazino [1, 2-a] quinoline

 (+) 1-3-(2-phthalimidethyl) 1-2,3.44 a, 5, 6-hexahi draw 1 H-virazino [1, 2-a] quinoline (0.80 g) And 80% hydrazine hydrate (0.32 ml) were reacted in the same manner as in Reference Example 1 and worked up to obtain the desired compound (0.51 g, quantitative).

Specific rotation ^{(. [Α] 2 *)} : + 1 2. 6 ° (C = 1. 0 0, E t OH); IR spectrum _{(CHC 1 3) cm- ':} 2 94 5, 282 3, 1 6 02;

NM R spectrum _{(CDC l 3) S p pm} :.. 1. 58 (2 H, brs), 1 68 - 2. 0 1 (2 H, m) 1. 95 (1 H, t, J = 1 0.6 Η ζ), 2.24 (1Η, dt, J = 3.2 2 ζ, J = 11.4 4 Η), 2.45 (2Η, t, J = 6.1 1) 65). 2.65-2.75 (1 ,, m). 2.75-3.10 (5 Η .m), 2.83 (2 Η, t, J = 6.1 Η) , 3.75 (1Η, d, J = 11.8 8), 6.69 (1Η, t, J = 7.3Η), 6.80 (1Η, d, J = 8.2 Η), 6.98 (1 Η, d, J = 7.3 Η), 7.09 (1 Η, t, J = 8.2 2).

 Reference Example 1 3

 Monochloride 2-biradinoyl

2-Virazinecarboxylic acid (1.0 g) was suspended in tetrahydrofuran (5 ml), and dimethylformamide (0.4 ml) and oxalyl chloride were added under a nitrogen atmosphere and ice-cooled stirring. (0.83 ml) was added, and the mixture was stirred for 30 minutes in a room S. The solvent was distilled off under reduced pressure to obtain the desired compound (1.15 g, quantitative). Test example 1

5-Η Τ, _Α receptor binding test

 After decapitation of a rat (male Wistar rat, weighing 200-300 g, Japan SLC), the brain was removed and the hippocampus was removed. After measuring the weight, 10 volumes of 5 OmM Tris-HCl buffer (pH 7.7) was added, and the mixture was homogenized with voritrone. To the pellet obtained by centrifugation (39000 Xg, 15 minutes, 4), 10 times the above buffer was added, and incubated at 37 ° C for 10 minutes. Again, the pellet obtained by centrifugation was washed once with 10 times the amount of the above buffer solution, and then the amount of protein was measured, and diluted with the above buffer solution to 200 / X g protein ml.

Manganese chloride (2 mM final) was added to the hippocampal membrane suspension obtained in this manner, and the mixture was incubated at 37 for 30 minutes. The hippocampus Makukaka «solution (0. 5 m l) in the labeled with tritium 8 arsenide Dorokishi 2 jib port Biruaminote Bok Lalin (final澳度0. 5 nM, or less ^[3 H] one 8 - 0 H- DPAT abbreviated) and test compound ^{(1 0- 1 ° ~ 1 0-} 7 M) was added, Inkyube and Bok 25 for 40 minutes. After the incubation was completed, the radioactivity bound to the membrane was measured with a liquid scintillation counter. From ^[3 H] one 8- 0 H- DP AT binding inhibition rate of the test compound in each * degree was calculated concentration (IC _so value) showing 50% inhibition.

 Test example 2

 Stress EEG Measurement (Effects on the α-band component of cerebral cortical EEG added when mental stress is applied)

 Male Wistar male rats (weight: 250-350 g, Japan SLC) were used in each group. Basically, the experiment was performed in accordance with the method of Iwat aanddMikuni, {Psychopharmacology. 71, 117 (1980).] [Psychopharmacology. 71, 117 (1980)].

A pair of silver bulb electrodes (diameter: 0.5 mm) were attached to the sensory motor area to record the EEG of animals under ventral valpital anesthesia (50 mg Zkg, i.p.). At the same time, they were fixed in a socket with dental cement, and intravenously injected with benicillin G to prevent infection. Used in experiments after wound healing for at least one week after surgery did.

 For the experiment, place the animal in a clear acrylic observation box (200 x 300 x 500 mm, stress cage) with a grid (straight S: 5 mm, spacing: 10 mm) on the floor. 4 After leaving for 5 seconds, apply power for 15 seconds (duration: 0.3 milliseconds, 100 V square wave pulse at 10 Hz). return. After repeating this operation about 15 times per minute, the animals were placed without stress on the stress cage (mental stress load), the brain waves for 10 seconds were recorded, and frequency analysis was performed. The power was analyzed using AT AC 450 (Nihon Kohden). Separately, the brain waves of the same time (10 seconds) were recorded and analyzed in the breeding cage, and only animals that had an alpha wave band component under stress of 130% or more of those in the breeding cage at rest were selected. Then, a pairedt-test test was performed to confirm that the addition was significant (P <0.05), and then used in an experiment for examining the drug effect. All test compounds were suspended in 0.596 CMC or 0.5% tragacanth solution, the concentration was adjusted to give a dose volume of 1 ml / kg, and the solvent was forcibly applied to the control group. Orally or intraperitoneally. At 15, 30, 45 and 60 seconds after the administration, the same mental stress was applied as described above, and the ratio of α-blow zone component was determined over time. The average α-band component ratio at each time after administration with respect to the average α-band component ratio before administration was tested using the pairedt-test, and it became significantly (P <0.05) significant in two consecutive time zones. Was determined as (+).

As a result of the test, the compounds of Examples 2, 8, _{22, 22} , 34, ₄₁ , 44, 49, 50 or ₅₉ showed a strong 5- _HTIA receptor _agonizing action and excellent mental _stress . It also showed a sedative effect on loess and an anti-phantom effect.

 Formulation Example 1

 Hard capsule

By filling each of the quasi-dichotomous hard gelatin capsules with 100 mg of the powdered compound of Example 8, 150 mg of lactose, 50 mg of cellulose and 6 mg of magnesium stearate, A unit capsule is manufactured, washed, and dried to obtain a hard capsule. [Industrial applicability]

 The hexahydrovirazinoquinoline derivative (I) or (II) or a pharmacologically acceptable salt thereof according to the present invention has an excellent 5-HT receptor agonistic action, a sedative action against mental stress, or an antipsychotic effect. With low toxicity or side effects (especially drowsiness), anxiety, g-disease, hypertension, schizophrenia, sleep labor, migraine, sexual dysfunction, motion sickness, dizziness or senile dementia symptoms ( It is useful as a therapeutic or preventive (especially therapeutic) especially for delirium.

 When the compound (I) or (II) of the present invention or a pharmacologically acceptable salt thereof is used as a therapeutic or preventive agent (especially a therapeutic agent) for the above-mentioned neurological disease, the compound itself or an appropriate drug may be used. Mix with physiologically acceptable excipients, diluents, etc. and administer orally with tablets, capsules, granules, powders or syrups, or parenterally with injections or suppositories can do.

These preparations may contain excipients (e.g., lactose, sucrose, dextrose, mannitol, sugar derivatives such as sorbit; corn starch, masuzuki starch, alpha-starch, dextrin, carboxymethyl starch, etc.). Starch derivatives; Cellulose derivatives such as quenched cellulose, low S-substituted hydroxybu mouth cellulose, hydroxypropyl methylcellulose, carboxymethylcellulose, carboxymethylcellulose calcium, internally drawn carboxymethylcellulose sodium; gum arabic : Dextran; burlan: light anhydrous silicic acid, synthetic aluminum silicate, silicate derivative such as magnesium metasilicate aluminate; phosphate derivative such as calcium phosphate; carbonate derivative such as calcium carbonate; Sulfate derivatives such as calcium ruthenate, etc., excipients (for example, the above-mentioned excipients; gelatin, polyvinylidene lidone, magrogol, etc.), disintegrants (for example, the above-mentioned excipients: Koku mouth Chemically decorated starches such as scarmellose sodium, carboxymethyl starch sodium, cross-linked polyvinylidolinidone, starch, cellulose derivatives, etc., lubricants (eg, talc: stearic acid; calcium stearate, stearin) Gold salts of stearic acid such as magnesium acid: colloidal silica; luxes such as veegum and gay mouths: lactic acid; glycols: glycols such as fumaric acid and adibic acid Boronic acids; sodium carboxylate such as sodium benzoate; sulfates such as sodium sulfate; leucine: lauryl sulfate such as sodium lauryl sulfate, magnesium lauryl sulfate such as magnesium sulfate: silicic anhydride Silicic acids such as hydrated silicic acid; starch derivatives in the above-mentioned K-form); stabilizers (eg, para-oxybenzoic acid esters such as methylparaben and propylparaben; chlorobutanol, benzyl alcohol, phenyl) Alcohols such as ethyl alcohol; benzal conidum; phenols such as phenol and cresol; thimerosal; acetic anhydride; sorbic acid, etc.), »taste« odorants (eg, commonly used sweeteners, acidulants) , Flavors, etc.), diluents, solvents for injections (eg, water, ethanol , Glycerin, etc.) and the like. The dosage varies depending on symptoms, age, etc., but in the case of oral administration, the lower limit is 1 mg (preferably 10 mg) and the upper limit is 200 mg (preferably 40 mg) per dose. In the case of intravenous administration, a lower limit of 0.1 mg (preferably 1 mg) and an upper limit of 500 mg (preferably 300 mg) should be administered to adults at a time. On the other hand, it is desirable to administer 1 to 6 times a day depending on the symptoms.

Claims

Claims General formula (I)

 (I) or general formula (II)

CH ₂ ) _m — C0NHR6

 (ID

[Where,

R ¹ represents a group having the formula: CO—R ³ ,

R ² represents a hydrogen atom,

Or R ¹ and R ² represent a group having the general formula (III) or (IV) formed together with the nitrogen atom to which they are bonded,

(IV)

(E II) R ³ is a C> -C alkyl group, C ₃ — C,. A cycloalkyl group, a C ₆ -C aryl group which may have 1 to 3 E substituents selected from the same or different from the following S substituent group A, and which are the same as or different from the S substituent group A below A C ₇ —C _<e aralkyl group, a mono C ₃ —C ₁₀ cycloalkylamino group, which may have 1 to 3 substituents, which are the same or different from the following E group A Mono-Cs-Carylamino which may have 1 to 3 S-substituents or 1 substituent selected from the following Substituent Group A, and may be fused to a benzene ring. A 5- or 6-membered aromatic heterocyclic group (the heterogeneity is one or two heteroatoms selected from the same or different from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom) Including)

R ⁴ and R ⁵ are the same or different and represent a water purple atom or a C> -C 6 alkyl group;

R ⁶ represents a Cs—C aryl group which may have 1 to 3 S substituents selected from the same or different from the following substituent group A,

Substituent group A includes a halogen atom, d-cβ alkyl group, halogen c, -c alkyl group, -C 6 alkoxy group, -C alkoxy C _t -C alkyl group, d -C alkylthio group, 1 to C ₆ -C aryl group which may have 3 substituents (the S substituent is halogen, C i -C alkyl or C i -C alkoxy), hydroxyl group, thiol group, amino group, protection It has been Amino groups, carboxy sheet group, carboxy d - a C alkoxycarbonyl group, a force Rubamoiru group, Shiano group or a nitro group, - C alkyl group, formyl group, C ₂ - C Arukanoiru group, C ₂

 X represents a methylene or acid purple atom,

 Represents an integer of 2 to 6. Or a pharmacologically acceptable salt thereof.

2. In claim 1, R ³ is a d-C * alkyl group, 1-methylhexyl group, 1-ethylpentyl group, 1-bromovirbutyl group; cyclopentyl group, cyclohexyl group; , C _t one Ci alkyl, Furuoromechiru, Jifuruo Romechiru, preparative Rifuruoromechiru, 2 Furuoroechiru, 2. 2- Jifuruoroechi , 2,2,2-Trifluoroethyl, C, -C alkoxy, methoxymethyl, ethoxymethyl, methylthio, ethylthio, phenyl, 4-fluorophenyl, 4-methylphenyl, 4-methoxyphenyl, hydroxyl, thiol, amino, amino May have 1 to 3 substituents which may be the same or different and are selected from the group consisting of cetylamino, carboxy, carboxymethyl, formyl, acetyl, methoxycarbonyl, ethoxycarbonyl, rubamoyl, cyano and nitro. Or naphthyl groups: Fluorine, chlorine, C! -Alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2.2,2-trifluoroethyl, monoalkoxy, methoxymethyl, methylthio, phenyl, 4-fluorophenyl, 4-methylphenyl A benzyl group optionally having 1 to 3 It substituents, which may be the same or different and selected from the group consisting of methoxyphenyl, cyano and nitro; cyclopentylamino group or cyclohexylamino group; Purple, CC alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 1 C <alkoxy, methoxymethyl, methylthio, phenyl, 4-fluorophenyl, 4 —Methyl Hue A phenylamino group which may have 1 to 3 substituents, which may be the same or different and is selected from the group consisting of toluene, 4-methoxyphenyl, cyano and nitro; or halogen, C-C alkyl, Fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, (-C-alkoxy, methoxymethyl, ethoxymethyl, methylthio, ethylthio, fuynyl, 4-fluoro Selected from the group consisting of phenyl, 4-methylphenyl, 4-methoxyphenyl, hydroxyl, thiol, amino, acetylamino, carboxy, carboxymethyl, formyl, acetyl, methoxycarbonyl, ethoxycarbonyl, kylbamoyl, cyano and nitro Has one SS substituent Hexahydrovirazinoquinoline derivative having the general formula (I), which is a pyrrolyl group, a pyridyl group, a virazinyl group, a pyrimidinyl group, a bilidazinyl group, an indolyl group, a quinolyl group, a furyl group or a cyenyl group; Its pharmacologically acceptable Salt.

3-In claim 1, wherein R ³ is butyl, isobutyl, s-butyl, t_butyl, 1-ethylpentyl; cyclopentyl or cyclohexyl; Purple, C! -C4 alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2.2-difluoroethyl, 2,2,2-trifluorethyl, C, 1C-alkoxy, methoxymethyl, methylthio, phenyl, 4-fluorophenyl Phenyl groups which may have 1 to 3 fi-substituted groups selected from the same or different from the group consisting of: 4-methylphenyl, 4-methoxyphenyl, cyano and nitro: benzyl group, fluormethylbenzene Benzyl group, dichlorobenzyl group, dichlorobenzyl group, trifluoromethylbenzyl group, methylbenzyl group, dimethylbenzyl group, trimethylbenzyl group, methoxybenzyl group, cyanobenzyl group, nitrobenzyl group; Cyclohexylamino group; phenylamino group, Fluorophenylamino, cyclophenylamino, difluorophenylamino, dichlorophenylamino, trifluoromethylphenylamino, triamino, xylylamino, mesitylamino, methoxyphenylamino Mino group, cyanophenylamino group or nitrophenylamino group: or fluorine, salt purple, C! -C * alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2 — trifluorethyl, CL-alkoxy, methoxymethyl, methylthio, phenyl, 4-fluorophenyl, 4 A pyridyl group, a virazinyl group, an indolyl group, a quinolyl group, a furyl group, which may have one substituent selected from the group consisting of monomethylphenyl, 4-methoxyphenyl, cyano and nitro; Hexahydrovirazinoquinoline derivative having a general formula (I), which is a phenyl group, or a pharmaceutically acceptable salt thereof.

4. In claim 1, R ³ is t-butyl, 1-ethylpentyl, cyclohexyl, phenyl, fluorophenyl, cyclophenyl, difluorophenyl, dichlorophenyl, Trifluoromethylphenyl, tril, xylyl, mesityl, methoxyphenyl, cyanophenyl, Trophenyl group, benzyl group, phenylamino group, 2.4-difluorophenylamino group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, virazinyl group, 3-methylbirazinyl group, 1-methyl-2-i N-drill, 2-quinolyl, 3-quinolyl, 4-quinolyl, 2-furyl, 3-furyl, 2-phenyl, 3-phenyl, 5-fluoro-2-phenyl Group, 5-methyl-2-phenyl, 3-methyl-2-phenyl, 5-methyl-2-phenyl, 3-methoxy-2-phenyl, 5-fluoro-3-phenyl, 5-chloro Having the general formula (I), which is a 3-thenyl group, a 4-methyl-3-thenyl group, a 5-methyl-3-thenyl group, a 4-methoxy-13-thenyl group, or a 5-methoxy-3-thenyl group; Kisahi Drovilaj Kino Li down derivatives or pharmacologically acceptable salts thereof.

5. In claim 1, R ³ is a fuundyl group, a 2-fluorophenyl group, a 3-fluorophenyl group, a 4-fluorophenyl group, a 2,3-difluorophenyl group, a 2,4 —Difluorophenyl group, 2,5-difluorophenyl group, 2,6-difluorophenyl group, 3,4-difluorophenyl group, 3,5-difluorophenyl group, 3,4-dichlorophenyl group, p-tolyl group , 3-trifluoromethylphenyl group, 4-trifluoromethylphenyl group, 2-methoxyphenyl group, 3-pyridyl group, virazinyl group, 1-methyl-2-indolyl group, 4-quinolyl group, 2-furyl, 2-phenyl, 3-phenyl, 5-chloro-2-phenyl, 3-methyl-2-phenyl, 5-methyl-2-phenyl or 4-methoxy-3-phenyl There is a general formula A hexahydrovirazinoquinoline derivative having (I) or a pharmaceutically acceptable salt thereof.

6. In claim 1, R ³ is a phenyl group, a 2,3-difluorophenyl group, a 2,4-difluorophenyl group, a 2,5-difluorophenyl group, a 3,4 dichlorophenyl group. , A virazinyl group, a 2-phenyl group, a 3-phenyl group, a 5-chloro-2-phenyl group, a 3-methyl-2-phenyl group, a 5-methyl-2-phenyl group or a 4-methoxy-3-phenyl group. A hexahydrovirazinoquinoline derivative having the general formula (I) or a pharmaceutically acceptable salt thereof.

7. In claim 1, R ³ is a phenyl group, 2,4-difluorophene. Hexahydrovirazinoquinoline derivative represented by the general formula (I), which is a nyl group, a birazinyl group, a 2-phenyl group or a 5-methyl-2-phenyl group, or a pharmacologically acceptable salt thereof.

8. At a claim 1, wherein, R 'and R ^2, together with the nitrogen atom to which they are attached, 2, 4-Jiokiso 3 thiazolidyl group, 5-mono C, - C alkyl one 2, Hexahydrovirazinoquinoline derivative having the general formula (I), which is a 4-dioxo 3-thiazolidyl group or 5,5-di-, -C * alkyl-2,4-dioxo-3-thiazolidyl group or a phthalimidyl group, or a pharmacology thereof. Top acceptable salts

9. In claim ¹ , R ¹ and R ² together with the nitrogen atom to which they are attached are 2,4-dioxo-3-thiazolidyl groups, 5-methyl-2,4-dioxo-3 —Thiazolidyl group, 5,5-dimethyl-2,4-dioxo-3-thiazolidyl group, 5-methyl-5-ethyl-2,4-dioxo-3-thiazolidyl group, 5-ethyl-2,4-dioxo-3-thiazolidyl group, 5, Hexahydrovirazinoquinoline derivative having the general formula (I) or a pharmacologically acceptable salt thereof, which is a 5-diethyl-2.4 dioxoxo 3-thiazolidyl group or a 5-isopropyl-12,4-dioxo-3-monothiazolidyl group, having the general formula (I).

10. In claim 1, R ¹ and the force together with the nitrogen atom to which they are attached, 2.4-dioxo-3-thiazolidyl group, 5,5-dimethyl-2,4-dioxo 3- Hexahydrovirazinoquinoline derivative having the general formula (I), which is a thiazolidyl group or 5-isopropyl-2,4-dioxo- 13-thiazolidyl group, or a pharmaceutically acceptable salt thereof.

1 1. At a claim 1, wherein, R 'and R ^2, together with the nitrogen atom to which they are attached, 5, 5-dimethyl-2, 4-Jiokiso 3 thiazolidyl group or 5- isopropyl Building Hexahydrovirazinoquinoline derivative having a general formula (I), which is a 2,4-dioxo-3-thiazolidyl group, or a pharmacologically acceptable salt thereof.

1 2. In Claim 1, R ^e is fluoroviolet, salt purple, C, 1 C * alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl , 2, 2-Jifuruoroechiru, 2, 2, 2-preparative Rifuruoroechiru, C, one C ₄ § alkoxy, main Bok Kishimechiru, methylthio, phenyl, 4 one Furuorofuweniru, 4 one-methylphenyl, 4-main Tokishifue sulfonyl, Shiano and nitro A hexahydrovirazinoquinoline derivative having the general formula (II) or a pharmaceutically acceptable salt thereof, which is a phenyl group optionally having 1 to 3 B-substituents selected from the same or different from the group consisting of Salt.

1 3. In the scope of the lecture, in paragraph 1, R ⁶ is phenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2,3-difluorophenyl, 2,4- Difluorophenyl, 2,5-difluorophenyl, 2,6-difluorophenyl, 3,5-difluorophenyl, 3,4-dichlorophenyl, p-tolyl, 3-trifluoromethyl Hexahydrovirazinoquinoline derivative having a general formula (II), which is a phenyl group, a 4-trifluoromethylphenyl group or a 2-methoxyphenyl group, or a pharmaceutically acceptable salt thereof.

14. The hexahydrovirazinoxoline derivative having the general formula (II) or a pharmacologically acceptable salt thereof, wherein R ⁶ is a phenyl group in the first scope of the present invention.

 1 5. The hexahydrovirazinoquinoline derivative or a pharmaceutically acceptable salt thereof according to any one of the claims 1 to 14, wherein X is methylene.

 1 6. A hexahydrovirazinoquinoline derivative or a pharmacologically acceptable salt thereof, wherein m is an integer of 2 to 4 in the scope of one subject matter selected from claims 1 to 15.

 1 7. A claim according to any one of claims 1 to 15, wherein m is 2 or a hexahydrovirazinoquinoline derivative or a pharmaceutically acceptable salt thereof.

1 8. The hexahydrovirazinoquinoline derivative wherein m is 4 or a pharmacologically acceptable salt thereof according to the claim selected from the claims K to 1 to 15 in the K box.

1 9. In claim 1, the protecting group of “protected amino group” is Le group, C ₂ - C Arukanoiru group: halogen or C [- were匱換by C alkoxy C ₂ - C Arukanoiru groups; unsaturated C - C Arukanoiru group; Nono androgenic,

C ■ -C alkyl, -C alkoxy, C ₂ -C alkoxycarbonyl

, C one C ₁₄ may be substituted with § Li Lumpur or two Toro, C ₇ - C _IS § Li Rukaru Boniru group; halogen or preparative Li C, - may be s conversion in C alkylsilyl, C - A C ₅ alkoxycarbonyl group; a C ₃ -C alkenyloxycarbonyl group;

C ₈ one C, ₆ Arirujikarubo alkenyl; C _tau one C "Ararukiru group;. Or main Bok carboxymethyl or may be substituted with nitro port C _e - C _s Kisahi to a § Lal Kill O alkoxycarbonyl group A drobirazinoquinoline derivative or a pharmacologically acceptable salt thereof.

 20.3- (2-benzamidoethyl) -1-2,3,4,4a, 5,6-hexahydro 1H-virazino [1.2-a] quinoline,

 3- (4-benzamidebutyl) 1-2,3,4,4a, 5,6-hexahydro-1H-birazino [1,2-a] quinoline,

 3- [4- (2,4-difluorobenzamide) butyl] 1,2,3,4,4a, 5,6-hexahi draw 1H-Virazino [1,2—a] quinoline ,

 3- [4- (2-Virazinecarbonylamino) butyl] 1,2,3,4,4a, 5.6-hexahydro-1H-birazino [1,2-a] quinoline,

 3,4- [2- (10-tenylamino) butyl] 1-2,3,4.4a.5,6-hexahidraw 1H-Virazino [1,2-a] quinoline,

 3- [4- (5-Methylthiophene-1-2-carbonylamino) butyl] 12,3,4,4a, 5,6-Hexahi Draw 1H-Virazino [1,2, -a] quinoline

3— [4— (5,5—Dimethyl-2,4-dioxothiazolidin-1-3-yl) butyl] -1-2.3,4,4a, 5,6-hexahidraw 1H—Virazino [1,2] -a] quinoline or

3- [4- (5-Isoprovir-1-2.4-dioxothiazolidin-1-3-yl) butyl] 1-2,3,4.4a.5,6-Hexahidraw 1H-Virazino [1.2 [A] Quinoline or a pharmaceutically acceptable salt thereof.

2 1. A 5-HT _IA receptor agonist comprising, as an active ingredient, a hexahydrovirazinoquinoline derivative or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 20.

 22. —General formula

Y— (CH ₂ ) _m --Rl

 R2

 (VII)

[Wherein, R ¹ represents a group having the formula CO—R ³ ,

R ² represents a hydrogen atom,

Or R ¹ and R ² represent a group having the general formula (III) or (IV) formed together with the nitrogen atom to which they are bonded,

(III) (IV)

R ³ is a d-C alkyl group, a C ₃ -C ₁₀ cycloalkyl group, a C _e -C aryl group which may have 1 to 3 substituents selected from the same or different substituent groups A A C ₇ -aralkyl group, a mono C ₃ -C ₁₀ cycloalkylamino group which may have 1 to 3 substituents which are the same or different from the following substituent group A, and the following substituent group A Mono C ₆ -aryl amino group which may have 1 to 3 substituents selected from the same or different and may have 1 substituent selected from the following S group A A 5- or 6-membered aromatic bi-violet ring group which may be fused to a benzene ring (the bi-violet ring is the same or different from the group consisting of Containing one or two selected heteroatoms).

R ⁴ and R ⁵ are the same or different and each represent a hydrogen atom or a C, -C alkyl group; And

E Substituent group A includes halogen atom, C, -C alkyl group, halogeno ^ -C alkyl group, -C alkoxy group, -C alkoxy-C alkyl group, C, -C alkylthio group, 1 to 3 C ₆ -C aryl group which may have a substituent (the g-substituted group is halogen, -C alkyl or -C, alkoxy), hydroxyl group, thiol group, amino group, protected amino group, carboxy group Shi group, carboxy C i - C alkyl group, formyl group, C ₂ - c _s Arukanoiru groups, C ₂ - C alkoxycarbonyl group, a force Rubamoiru group, a Shiano group or a nitro group,

 m represents an integer of 2 to 6,

Y represents a leaving group. And a compound having the general formula

 (VIII)

(Wherein X represents a methylene or oxygen atom).

 (I)

(Wherein, R ¹ , R ² , X and m have the same meanings as described above.) A method for producing a hexanehydrobirazinoquinoline derivative represented by the formula:

2 3. In Claim 22

R ¹ and R ² , together with the nitrogen atom to which they are attached, are 2,4-dioxo-3-monothiazolidyl groups, 5-mono C, -C alkyl-1,2,4-dioxo-3-thia A zolidyl group or a 5,5-diC, -C * alkyl-1.2.4-dioxo-3-thiazolidyl group or a phthalimidyl group;

 X force methylene,

 Y is a salt purple, odor purple or iodine atom; a methanesulfonyloxy group or an ethanesulfonyloxy group; a trifluoromethanesulfonyloxy group, a 2,2,2-trichloromouth ethanesulfonyloxy group or a pentafluoro group A process for producing an ethanesulfonyloxy group; or a benzenesulfonyloxy group, a p-toluenesulfonyloxy group or a mesitylenesulfonyloxy group.

2 4. In claim 22,

R ¹ and are, together with the nitrogen atom to which they are attached, a 5,5-dimethyl-2,4-dioxo-3-thiazolidyl group or a 5-isopropyl-12,4-dioxo-13-thiazolidyl group;

 X is methylene,

 m is 4;

 The production method wherein Y is a chlorine, odor purple or iodine atom.