TWI283678B - Pyrazolo[3,4-b]pyridine compounds, and their use as phosphodiesterase inhibitors - Google Patents

Abstract

The invention relates to a compound of formula (I) or a salt thereof: wherein: R1 is C1-4alkyl, C1-3fluoroalkyl, -CH2CH2OH or -CH2CH2CO2C1-2alkyl; R2 is a hydrogen atom (H), methyl or C1 fluoroalkyl; R3 is optionally substituted C3-8cycloalkyl or optionally substituted mono-unsaturated-C5-7cycloalkenyl or an optionally substituted heterocyclic group of sub-formula (aa), (bb) or (cc); in which n1 and n2 independently are 1 or 2; and in which Y is O, S, SO2, or NR10; or R3 is a bicyclic group (dd) or (ee); and wherein X is NR4R5 or OR5a. The compounds are phosphodiesterase (PDE) inhibitors, in particular PDE4 inhibitors. Also provided is the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment and/or prophylaxis of an inflammatory and/or allergic disease in a mammal such as a human, for example chronic obstructive pulmonary disease (COPD), asthma, or allergic rhinitis.

Description

1283678 发明Invention Description: TECHNICAL FIELD The present invention relates to pyrazolopyridine compounds, which are produced by the intermediates in the methods, and pharmaceutical compositions containing the compounds. The invention also relates to the use of pyrazolopyridine compounds in therapy, for example as inhibitors of diterpene phosphate enzymes and/or for the treatment and/or prevention of inflammatory and/or over-sex diseases, such as chronic obstructive pulmonary disease ( C0PD), asthma or allergic rhinitis. [Prior Art] US 3,979,399, US 3,_, 546 and US 3,966,746 (ERSq secret & The amine group NRsR4 may be a non-cyclic amine group, the center of which may be hydrogen, a lower alkyl group (e.g., butyl group), a phenyl group, etc.; and NR3 R4 may alternatively be a 3-6-membered heterocyclic group. For example, tetrahydrop-biheptyl, hexahydropyridyl and hexahydroquinone. These compounds are disclosed as central nervous system depressants and can be used as a neuroleptic, analgesic and hypotensive agent. US 3,925,388, US 3,856,799 US 3,833,594 and US 3,755,340 (ER·Squibb & Sons) are 4-amino-based derivatives of p-suppressive [3,4-b] bite-5-acids and esters. NR3R4 may be a non-cyclic amine group, wherein R4 may be each hydrogen, lower alkyl (e.g., butyl), phenyl, etc.; Nr3r4 may alternatively be a 5-6-shell hetero-group There is another nitrogen, such as tetrahydrop-pyrrolyl, hexahydropyridyl, pyrazolyl, pyrimidinyl, hydrazine or hexahydropyrryl. These compounds are mentioned as central nervous system depression. It can be used as a neuroleptic or tranquilizer with anti-inflammatory and analgesic properties. These compounds are mentioned to increase the intracellular concentration of adenosine-3,5,-cyclic monophosphate, and 87841-960303- .doc -10- 1283678 to alleviate the symptoms of asthma. H. Hoehn et al., // //eteraqyc/· C7^m·, 1972, 9(2), 235-253 Reveal a series of 1H-pyrazolo[3, 4-7] Pyridine-5-carboxylic acid derivative having 4-hydroxy, 4-chloro, 4-alkoxy, 4-indenyl and 4-amino substituents. CA 1003419, CH 553 799 and T· Denzel , Archiv der Pharmazie, 1974, 307(3), 177-186 discloses unsubstituted 4,5-disubstituted 1H-leaf and [3,4-b]p ratios at the 1-position. 2002 Japanese Laid-Open Patent Application No. -2002-20386-A (Ono Yakuhin Kogyo KK), published on January 23, discloses a compound of the formula p:

JP-2002-20386-A (Ono) wherein R1 represents 1) a group -OR6, 2) a group -SR7,3) a C2-8 group, 4) a nitro group, 5) a cyano group, 6) a hydroxy group or C1-8 alkoxy substituted C1-8 alkyl, 7) phenyl, 8) group -C(0)R8,9) group -S02NR9R10,10) group_NRuS02R12,11) group-NR13C (0) R14 or 12) group -CH=NR15. R6 and R7 represent i) a hydrogen atom, ii) a C8-8 alkyl group, iii) a C1-8 alkyl group substituted by a C1-8 alkoxy group, iv) a trihalomethyl group, v) a C3-7 cycloalkyl group, Vi) C1-8 alkyl substituted by phenyl or vii) 3-15 membered mono-, di- or tricyclic heterocyclic ring containing 1-4 nitrogen atoms, 1-3 oxygen atoms and/or 1- 3 sulfur atoms. R2 represents 1) a hydrogen atom or 2) a C1-8 alkoxy group. R3 represents 1) a hydrogen atom or 2) a C1-8 alkyl group. R4 represents 1) a hydrogen atom, 2) a C1-8 alkyl group, 3) a C3-7 cycloalkyl group, 4) a C1-8 alkyl group substituted by a C3-7 cycloalkyl group, and 5) can be 1-3 87841- 960303-中.doc •11 - 1283678 _Atom substituted phenyl, or 6) 3-15 member mono-, di- or tricyclic heterocyclic ring containing 氮 one nitrogen atom, 1-3 oxygen atoms and / Or 1-3 sulfur atoms. R5 represents 1) a hydrogen atom, 2) a C8-8 alkyl group, 3) a C3-7 cycloalkyl group, 4) a C1-8 alkyl group substituted by a C3_7 cycloalkyl group, or 5) may be substituted by 1 to 3 substituents. Substituted phenyl. In the group R3, a hydrogen atom is preferred. In the group R4, a methyl group, an ethyl group, a cyclopropyl group, a cyclobutyl group or a cyclopentyl group is preferred. The compound of JP-2002-20386-A is converged to have PDE4 inhibitory activity and can be used for the prevention and/or treatment of inflammatory diseases and many other diseases. EP 0 076 035 A1 (ICI USA) discloses that pyrazolo[3,4_b]pyridine derivatives act as central nervous system depressants and act as tranquilizers or neuroleptic agents for relieving anxiety and stress. Compound carbazole (cartazolate), 4-(n-butylamino)+ethyl·1H_pyridox[3,4-b]-external b-yt-5-deoxyethyl ester know. Jw· Daly et al., Med·Chem·and Hunger, 1994, 4, 293-306 and D· Shi et al., 襄# 发广呀宏, 1997, 42, 41-56 Reveal a series of 4-(amino) Substituted 1H pyrazolo[3,4-7]pyridine-5-carboxylic acid derivative, including 4-cyclopentylamino + methyl-1H-pyrazolo[3,4_b]pyridine-5-carboxylic acid B Ester and its affinity and antagonistic activity at the A- and octa-ag-adenosine receptors, and the affinities of the various binding positions of the GABAa-receptor channel are revealed in the following papers. S. Schenone et al., and (10) Sin Han/. CTzem. jLeii., 2001, 11, 2529-2531 and F. Bondavalli et al., 2002, vol. 45 (published on October 22, 2002, according to The publication is published on the website, 09/24/2002), pages 4875-4887, revealing a series of 4-amino-1-(2-chloro-2-phenylethyl)-1Η·pyrazolo[ Ethyl 3,4-b]pyridine-5-carboxylate as an Ai-adenosine receptor ligand. 87841-960303·中.doc • 12-1283678 WO 02/060900 A2 presents the disclosure of a series of bicyclic heterocyclic compounds as MCP-1 antagonists for the treatment of allergic, inflammatory or autoimmune disorders or diseases, The compound has a -C(0)-NR4-C (0>NR5R6 substituent, including isoindole [5,4-b]pyridine and 1H-pyrazolo[3,4-7]pyridine (designated as pyridyl) Zoxao[5,4-b]pyridines, having a -C(0)-NR4-C(0)-NR5 R6 group as a 5-substituent, and optionally 1-, 3-, 4- And/or substituted at the 6-position. A bicyclic heterocyclic compound having a _c(0)NH2 substituent in place of the -C(9)-NR4-C(0)-NR5R6 substituent is disclosed in WO 02/060900 As a synthetic intermediate of -C(0)-NR4 -C(0)-NR5R6 substituted compound. It is generally desired to find a novel compound which binds to, and preferably inhibits, phosphodiesterase type IV (PDE4). The present invention provides a compound of formula (I) or a salt thereof (particularly a pharmaceutically acceptable salt thereof):

R1 is a Ch alkyl group, a Cu fluoroalkyl group, -CH2CH2〇H or an alkyl group; R2 is a hydrogen atom (H), a methyl group or a q-fluoroalkyl group; R3 is optionally substituted c3_8 cycloalkyl group or, as the case may be Substituted monounsaturated-C5_7 cyclodecyl, or substituted as a subtype (aa), (bb) or (ec), substituted 87841-960303-medium.doc-13- 1283678 cyclodyl group;

(iv) (bb) (cc)

Η2 wherein nl and η2 are independently 1 or 2; and wherein Y is 〇, S, S02 or NR10; wherein R10 is a hydrogen atom (η), q·4 alkyl (eg methyl or ethyl) 'Cl-2 Fluoroalkyl, ch2c(o)nh2, c(0)Nh2, c(0)_Ci-2 alkyl, c(〇)_Cl fluoroalkyl or alkyl; and wherein in R3, (^8 cycloalkyl Or a heterocyclic group of the formula (aa), (bb) or (cc) is optionally substituted with one or two substituents, the substituent being independently (for example) a keto group (=〇); OH; Ci-2 alkoxy; Ci-2 fluoroalkoxy (e.g., trifluoromethoxy); NHR21, wherein R21 is a hydrogen atom (H) or a Ci-5 linear alkyl group (e.g., hydrazine or Ci _4 linear) Alkyl); q · 2 alkyl; C! -2 fluoroalkyl (e.g., Ci fluoroalkyl ' such as -CH2F or -CHF2); ?αΐ2ΟΗ; -CH2CH2OH; -CH2NHR22, wherein R22 is H or (V2 alkyl ;-C(0)0R23, wherein R23 is a group; -C(0)NHR24, wherein R24 is Η or Ci-2 alkyl; _c(〇)r25, wherein alkyl; fluoro; hydroxyimino (= N-〇H); or (Ci-4 alkoxy)imino (=N-OR26, wherein R26 is c 4 alkyl); and any OH, alkoxy, fluoroalkyloxy or NHR21 Replace The group is not substituted at the R3 ring carbon attached (bonded) to the formula (I) _ NH- group, and is not bonded to the heterocyclic group (aa), (bb) or (cc) Y Wherein any one of the R3 ring carbons of the group is substituted; and wherein when R3 is an optionally substituted monounsaturated _C5-7 cycloalkenyl group, then the ring link is optionally one or two fluoro groups or The substituent of the C1-2 alkyl group is 87841-960303-medium doc -14 - 1283678, provided that if there are two substituents, they are not all calcined and bonded to the formula 1-win group R3 ring carbon does not participate in the ring-bonded double bond;

(dd) or R3 is subtype (dd): group:

The bicyclic ring wherein Y1, Y2 and Y3 are independently Ch2 or oxygen (〇), provided that no more than one of γΐ, Υ2 and Υ3 is oxygen (0); and X is NR4R5 or 〇R5a, wherein: 9 R is a hydrogen atom (H), a group; (: a trifluoroalkyl group; a pyridyl group, which is substituted by a substituent R11; and R is a hydrogen atom (H), (: a group of 8 groups; a gas of CH: ί a C3·8 cycloalkyl group substituted by a Ci-2 alkyl group; or _(αί2)Λ (:3·8 cycloalkyl group, optionally in the -(CH2)n4- moiety or in the C3_8 ring In the alkyl moiety, substituted by 2 alkyl, wherein η4 is 1, 2 or 3; or R is C; 2·6 alkyl is substituted by one or two independent substituents ri 1 ; The group R11, irrespective of any other Ri 1 substituents present, is: trans group (OH); Ch alkoxy; phenoxy; benzyloxy; _nr12ri3; 15-c(〇)Rl6; -NR15- C(0)_0-R16; 15-C(0)-secret R15^SC^R16; and any of the Ri 1 substituents, which are 〇H, alkoxy or -NRl 2r1 3 'will not be in any Any carbon atom substituted by R4 or R5 substituted alkyl (which is bound to the nitrogen of NR4R5) is substituted; or as #!^)/1-^;.)!^6;#!!;^12 ^.)]^12!^3;-^^19-C(0)NR12R13 ; .(CH2)n12-C(0)0R16 ; -(CH2)n12-C(0)0H ; -CHR19- 87841- 960303-中.doc -15- 1283678 c^6;.chr19^ 2, or _(CH2)nl2-CN; where n11 is 0, 1, 2, 3 or 4, and nl2 曷丄, 2, 3 or 4 Or R5 is <CH2)ni3_Het, where nl3 5 is 1, 2, 3 or 4, and Het is 4-, or a 7-week saturated or partially saturated heterocyclic ring containing _ or two independent, ^ ring An atom; any ring hetero atom present therein, on the same day, 'will not bind to the -(CH2)n"- partial base, and when η13 is 〇, it is not present in the nitrogen 4 and is not unsaturated Any ring nitrogen (meaning that it is not a double bond) is present, wherein Rl7 is as defined herein; and wherein one or two of the carbon ring atoms are independently substituted by Ci2 alkyl as appropriate; or the phenyl is ' Substituting one, two or three of the following base rings as appropriate. Atom; C!.6 alkyl (eg Q.4 alkyl or Cl.2 alkyl); Ci2 fluoroalkyl (eg trifluoromethyl) Cl 4 alkoxy (eg Cl 2 alkoxy); Ci 2 fluoro alkoxy (eg trifluoromethoxy); C 3-6 cycloalkyloxy; _C (0) Rl6a ; -C(〇)〇r30 ; -S(〇)2_Rl6a (eg alkylsulfonyl or Cl -2 alkyl _S〇2; R1 6 a_s(〇) plant NR! 5 a- (eg q alkane --S02-NH-) ; R7R8N-S(〇)2· ; q alkyl-c(〇>Rl5aN_s(〇)2_ ; alkyl-S(0)-, Ph-S(O)-, R7R8N -CO15; -NR15-C(0)R16; R7R8N; OH; C 4 alkoxymethyl; Cl-4 alkoxyethyl; Cb2; 1171181^(0)2<:112-; 2 alkyl-8(0)2-View 15&-〇12-;-(:112-(^;-ch2ch2-oh;-ch2-nr7r8;-CH2-CH2-NR7R8; -CH2-C(0 OR30; wherein n14 is o or 1; cyano (CN); Ar5a; or stupid, pyridyl or pyrimidinyl, wherein phenyl, pyridyl or pyrimidinyl is independently one or two 87481-960303- Medium .doc • 16-1283678 Fluoro, chloro, c^2 alkyl, Cl fluoroalkyl, Ci 2 alkoxy or. Fluoroalkoxy substituted, or wherein two adjacent substituents are taken together as "%"-^ or _0-(CH2)n 14 -0-, wherein ηι 4 is 1 or 2; wherein R7 and R8 Is independently a hydrogen atom (H); a Ci_4 alkyl group (for example, a Ci2 alkyl group such as a methyl group); (: a 3-6 cycloalkyl group; or a phenyl group, optionally substituted by one or two of the following groups: a fluorine group, a chlorine group Base, q.2 alkyl, q fluoroalkyl, (^-2 alkoxy or Ci fluoroalkoxy; or R7 together with R8 is _(CH2凫 or ·c(〇)_(CH2)n7_ Or -c(o)-(ch2)n 7 -c(0> or _(Ch2 )Λχ7 _(CH2 )Λ or 'where: n6 is 3, 4, 5 or 6, and n7 is 2, 3, 4 or 5 (n7 is preferably 2, 3 or 4), η8 and η9 and ηι〇 are independently 2 or 3 (preferably independently 2), and 乂7 is Ο or NR14, wherein Ri4 is H, Ci_2 alkyl Or c(〇)Me (preferably η or Ci-2 quinone); or R5 has the subtype (X), (y), (yl) or (8):

Wherein in subtype (X), n = 〇, liu; in subtypes (y) and (6), melon or 2; and in subtype (z), 1^==0, 1 or 2; In the subtypes (X) and (y) and (yl), none or one or two of A, B, D, E and F are independently nitrogen or nitrogen oxides "+_〇-) , the condition is that no more than one of A, B, D, E and F is nitrogen-oxide; and the remaining a, b, D, E and F are independently CH or CR6; the condition is that when in the subtype ( When η in X) is 〇, then one or two A, B, 87841-960303-nfi.doc -17- 1283678

D, E and F are independently nitrogen or nitrogen-oxide ^^_〇-), and no more than one of a, b, d, E and F is a nitrogen-oxide; wherein each R6, and any other present R6 is irrelevant, is a halogen atom; Ο-alkyl group (such as C! · 4 alkyl or qj alkyl); q _4 fluoroalkyl (such as q _2 fluoroalkyl); c1M alkoxy (such as Cl · 2 alkoxy); Ci 2 fluoroalkoxy; ^cycloalkyloxy; -C(0)R16a; -C(0)0R3(); -S(0)2-R16a (eg Cu alkylsulfonyl, meaning (: 2 alkyl-S02_ Ri6a_S(0) Factory service 151 (eg 〇12 alkyl-S02_NH_); R7r8n_S(0)2-; cBu 2 alkyl-C(9)-R15aN-S(0)2-; Ch alkyl-S(0 ··, Ph-S(o)-, R7R8N-CO-; -NR15-(:(0)1116; r7r8n; 〇H; Ch alkoxymethyl; alkoxyethyl; 〇: 卜2 alkyl _8(〇)2_(:112-, R7R8N-S(0)2-CH2_; Ci.2 alkyl-S(0)2-NR15a-CH2-; -CH2-0H; -CH2CH2-OH; -CH2 -NR7R8; -CH2-CH2-NR7R8; -CH2-C(0)0R3 0 ; wherein n14 is 0 or 1; cyano (CN); Ar5b; or phenyl, pyridyl or pyrimidinyl' wherein phenyl, pyridine The yl or pyrimidinyl group is independently substituted with one or two fluoro, chloro, alkyl, q fluoroalkyl, Q-2 alkoxy or fluorenyl 1 fluoroalkoxy groups; or two adjacent R 6 - is adopted as _Q_(CMe2 or (CH2)n14-0-, where ^ is "Ge 2; where R7 and R8 are as defined herein; wherein sub- (y) and (yl) are independent depending on the situation 6-member aromatic ring ring carbon

Substituted by a keto group (=0) (for example, subtype (y), as the case may be 87841-960303-medium.doc -18- 1283678

ϋ , or subtype (yl) may be Jj or / 〆)) wherein in sub-formula (8), G is 0 or S or NR9, wherein R9 is a hydrogen atom (H), a Ci-4 group or a Q-4 Fluorine-based; none, one, one or three of J, L, hydrazine and Q are nitrogen; and the remaining J, L, Μ and Q are independently CH or CR6, of which R6, and any other R6 present Irrelevant, as defined herein; or R4 and R5 are taken as -(CHJp1- or -C(0)-(CH2)p2_ or _(CH2)p3_x5-(CH2)p[or-C(〇)-x5 -(CH2)p5_, where: pl = 3, 4, 5 or 6 (preferably P = 4 or 5), p2 is 2, 3, 4 or 5 (p2 is preferably 2, 3 or 4), and The p3 and P5 lines are independently 2 or 3 (preferably independently 2), and X5 is 〇 or NR17; and wherein R4 and R5 are taken as -(CHJp1· or _C(〇HCH2)/_ When the NR4R5 heterocyclic ring is optionally substituted by an R18 substituent, wherein 1^8 is: Ci4 bond group (for example, Cl-2 base group); Cl-2 gas group, C3-6 soil base; Cl 2垸"oxy (not substituted at the ring carbon bonded to the nr4r5 ring nitrogen); q fluoroalkoxy (not substituted at the ring carbon bonded to the NR4R5 ring nitrogen); 0H (not bound to the NR4R5 ring) Nitrogen ring carbon Substituted); -(CH2)p7-C(0)R16, wherein P7 is 〇, 1, 2 or 3 (p7 is preferably 0 or 1); -((:Η2)ρ7<(0)0ί116 ; (CH2)p7-0C(0)R16; -(CH2)p7-C(0)NR12R13; -(CH2)p 7-NR15 C^R16 ; -(CH2)p7-NR15C(0)NR12R13 ; -(CH2 p 7-NR15 CCOPR16; -(CH2)p7-S02R16; -(CH2)p7-S02NR12R13; -(CH2)p7-NR15S02R16; -(CH2)p7-OH; -(CHd^-OR16; or phenyl, Substituted by one or two of the following groups: from an atom, (^-2 alkyl, q-fluoroalkyl, Ck alkoxy or (^fluoroalkoxy; 87841-960303-.doc -19- 1283678 or R4 and R5 are employed as defined herein or _c(〇)_(CH2)p2- or -(CH2)p3_x5_(CH2)p4_ or seven (〇)·χ5_(α^ρ5_, and wherein The NR4R5 heterocyclic ring is fused to a phenyl ring, optionally substituted on the phenyl group with one or two of the following groups: _ atom, Cm alkyl, Cl fluoroalkyl, Ci 2 alkoxy or fluoroalkoxy And alkyl, Cu fluoroalkyl; () 3-8 cycloalkyl; _(CH2)n4a-C3-6 cycloalkyl, wherein na is 1 or 2; phenyl, optionally with one or two of the following groups Substitution: Helium atom, (: 2 alkyl, trifluoromethyl, Ci 2 alkane Or a trifluoromethoxy group; or R5a has the formula (8), (9) or (8) as defined herein and wherein: R12 and R13 are independently oxime; (ν5 alkyl (eg Cl-3 alkyl); c36 naphthenic Or a phenyl group, optionally substituted with one or two of the following groups: a halogen atom, a q2 alkyl group, a (fluoroalkyl group, an alkoxy group or a cardinylfluoroalkoxy group; or R12 and R13 Is _(CH2)n6- or ·〇:(〇)-(αί2)η7- or -C(0)_(CH2)n7- <^(〇)- or -(012)1180^2-(( : 112) 119- or -(:(0)- and 12-((:112)1110-, where: 116 is 3, 4, 5 or 6 (116 is preferably 4 or 5), and 117 is 2, 3 4 or 5 (117 is preferably 2, 3 or 4), η8 and η9 and ηι〇 are independently 2 or 3 (preferably independently 2), and X12 is 0 or NR14a, wherein Ri4a is H, Ci 2 alkyl or c(〇)Me (preferably Η or (^-2 alkyl); R is a wind atom (Η), C _4 alkyl (such as tBu or Q · 2 alkyl, such as methyl) A-cycloalkyl; or phenyl, optionally substituted with one or two of the following groups: from atom, Q-2 alkyl, heart fluoroalkyl, alkoxy or heart fluoroalkoxy; R15a, Irrespective of other R15a, it is a hydrogen atom (H) or (V) 4 alkyl (eg η, 87841·96〇3〇3-中 doc -20- 1283678

Wu or Cu alkyl, such as methyl; R15a is preferably hydrazine or Cu alkyl, more preferably H);

Rl6 and R1U are independent:

Cb6 alkyl (eg (: 4 alkyl or (^. 2 alkyl); C 3 · 6 cycloalkyl (eg C5-6 cycloalkyl), optionally a keto group (=〇), 0H or Q a 2 alkyl substituent (for example, substituted at the 3- or 4-position of the c5 -6 cycloalkyl ring; and/or preferably unsubstituted c3-6 cycloalkyl); C3-6 ring Alkyl-CH2- (for example C5-6 cycloalkyl-CH2; pyridinyl (for example pyridin-2-yl), optionally substituted on one of the ring carbon atoms by one of the following: _ atom, alkyl, heart fluoroalkyl , Cl-2 alkoxy or heart fluoride alkoxy;

Ar5c ; phenyl, optionally substituted by one or two of the following groups: _ atom, Ci 2 alkyl, (^ fluoroalkyl, alkoxy or heart fluoroalkoxy; benzyl 'in the case of aromatic The carbon atom is substituted by one or two of the following groups: a halogen atom, a Ci 2 alkyl group, a Ci fluoroalkyl group, a Ci 2 alkoxy group or a q fluoro alkoxy group; or 4·, 5-, 6- Or a 7-membered saturated heterocyclic ring, which is attached at the ring carbon and contains one or two ring heteroatoms independently selected from 0, S and N; any ring nitrogen present therein is present as NR27, wherein R27 is η, Cl·2 alkyl or -C(〇)Me; and wherein the ring is optionally substituted at the carbon with a ^2 alkyl or keto (=〇) substituent, provided that the 'any keto group The (=〇) substituent is substituted at the ring-nitrogen ring-bonded to the carbon atom; wherein AP, Ar5b and Ar5c are independently 5_membered aromatic heterocycles, containing one 〇, 87841_96〇3〇3_ D〇c 21 - 1283678 S or NR15&in a 5-membered ring wherein the 5-membered ring may additionally contain one or two N atoms, and wherein the heterocyclic ring is optionally substituted on the ring carbon atom by one of the following : halogen atom, Cu alkyl group, (^ Fluoroalkyl, -CH2OH, -CHrOC^alkyl, OH (including keto tautomers thereof) or -CH2-NR28R29, wherein R28 and R29 are independently oxime or methyl; and R17 is a hydrogen atom (H) CV4 alkyl (eg (: 2 alkyl); CV2 fluoroalkyl; 〇3_6 cycloalkyl; -(CH2)p6-C(0)R16, wherein p6 is 〇, 1, 2 or 3 (p6 Preferably, it is 0); -(CH2)P6-C(0)NR12R13; -(CH2)p6-C(0)0R16; -(CH2)p6-C(0)0H; -S02 R16 ; -C(0) _CH2 -NR12 R13 ; -C(0)-CH2 -NR15 a - 3 alkyl; -CXCO-CIVO-Cu alkyl; or phenyl or aryl, wherein phenyl or benzyl is optionally in the aromatic carbon atom Substituted by one or two of the following groups: a halogen atom, an alkyl group, (^fluoroalkyl, Ci-2 alkoxy or (^fluoroalkoxy; R1 9 is a Ci -4 alkyl; -(CH2) N2 0 -OR2 〇, wherein η20 is 1, 2, 3 or 4, and R2G is a hydrogen atom (Η) or a Ch alkyl group; -CH(Me)-OH; -CH2-SH; _CH2-CH2-S- Me ; benzyl; or (4-hydroxyphenyl)methyl (ie, 4 hydroxy hydroxy); and R 3 〇 ' is independent of other R 3 G, is a hydrogen atom (H), Ci -4 alkyl or C3 _6 cycloalkyl;

Het1 'is not related to other Het1, is a 4-, 5-, 6- or 7-membered saturated heterocyclic ring, is attached at the ring carbon, and contains one or two ring heterocycles independently selected from 〇, s and N. An atom; wherein any ring-nitrogen system is present, wherein RS1 is deuterium, Ci 2 alkyl or -C(O)Me; and wherein the ring is optionally a Ci 2 alkyl or keto group at the carbon ( =0) Substituent substitution, provided that any keto (=〇) substituent is substituted at the ring-carbon atom bonded to the ring-nitrogen; 87841_96〇3〇3_.doc -22- 1283678 Yes: When R3 is a subgroup of the (bb) heterocyclic group, η1 is 1, and Y is NR1 G, then: (4) R1 G is not q-4 alkyl, q-2 fluoroalkyl or CH2C ( 0) NH2; or (b) R1 Q is methyl, and the compound is: 4-[(1-methylhexahydropyridyl)amino]-1-ethyl·1Η-pyrazole p,4- b] pyridine-5-carboxylate ethyl ester, 1-ethyl-N-(2-ethylbutyl)-4-[(1-methylhexahydropyridin-4-yl)amino]]1Η_pyrazole And [3,4_b]pyridine·5-formamide, 1-ethyl-indole-(4-fluorophenyl)-4-[(1-methylhexahydrop-butylide-4-yl)amino group ]-lH-p-pyrazolo[3,4-pyridinium-5-carboxamide or Ν-benzyl Small ethyl-4-[indolylmethylhexahydropyridin-4-yl)amino]-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide. In the case where X is OR5a, the compound is preferably not a compound wherein Ri is a fluorenyl group, X is OEt, and R3 is a cyclopentyl group. In an alternative embodiment of the invention, Ri is a Cl 4 alkyl group or a Cl-2 fluoroalkyl group. Alternatively or additionally, in an alternative embodiment of the invention, R2 is a hydrogen atom (H). Alternatively or additionally, in an alternative embodiment of the invention, R3 is C3-8 cycloalkyl or

a broad Y or heterocyclic group wherein Y is 〇, S, S〇2 or NR10; wherein R10 is hydrogen, Ch alkyl, Ci-2 fluoroalkyl, αοΚκ alkyl or c(o)-cf3; Wherein the 'C3-8' or the heterocyclic group in R3 is optionally substituted by a substituent of OH, q.2 alkoxy, trimethoxy or C!-2 alkyl; Wherein any of the hydrazine, alkoxy or trimethoxy substituents are not substituted at the (R3) ring carbon attached (bonded) to the formula (I)-ΝΗ- group, and are not bonded to the heterocycle 87841_96〇 Any of the (r3) ring carbons of the γ group of the 3〇3-中.doc -23- 1283678 group is substituted. Deuterated or otherwise, in an alternative embodiment of the invention, hydrazine is hydrogen, alkyl or (: 1-2 fluoroalkyl). Alternatively or additionally, in an embodiment of the invention selected Is a ^ 1-8 alkyl Cl_8 fluoroalkyl or C 3 · 8 cycloalkyl; or a phenyl group, optionally substituted with one or two of the following groups: a tooth atom, a CW group, a trifluoromethyl hydrazine, Cl oxy or difluoromethoxy; or R 5 has the subtype (8), (9) or (7): _(CH2)n

(X)

-(CH2

(z) where in the subtype (X), n = 1 or 2; in the subtype (y), m is called 2 or 2; and in the subformula (z), r = 1 or 2; In (X) and (y), none or one or two of A, b, D, E and F are nitrogen; and the remaining A, B, D, E and F are CH or CR6, wherein in the halogen atom , calcination base, Cl_4, calcination group, Ci2 alkoxy group, Ci2 gas-based alkoxy group, Ch-alkylsulfonyl group (Ci·2 calcination mother-), Ci 2 alkyl group, C1_4 alkoxymethyl group or

R7R8N-S02_, R7R8N-CO·, R7R8n, OH q·2 alkyl_S(VCH2·, wherein R7 and R8 are independently hydrogen or Ci 2 alkyl; wherein in subformula (z), G is o or S or NR9, wherein R9*Ci_4 alkyl or Ch fluorocarbon S; none or one or two of J, L, M and Q are nitrogen, and the remaining J, L, Μ and Q are CH or CR6, wherein R6 is as defined herein. In the alternatives to the specific embodiments of R4 and/or R5 above, in an alternative embodiment of the invention, 圮 and 圮 may be used together as _(cH2), where P1 = 3, 4 or 5 (preferably p1 == 4 or 5) 87841-960303-中.doc -24- 1283678 In an alternative embodiment of the invention, R3 is optionally replaced by C3·8 a heterocyclic group substituted with a cycloalkyl group or an Asian formula (aa), (bb) or (cc);

Wherein η1 and n2 are independently 1 or 2; and wherein γ is 〇, s, 8〇2 or >丨1110; wherein R10 is a hydrogen atom (H), a Q-4 alkyl group (e.g., methyl or ethyl) , q -2 fluoro-alkyl, ch2c(o)nh2, C(0)NH2, C(〇KV2 alkyl or ¢:(0)-(^ fluoroalkyl; and wherein 'C3-8 ring in R3 A halogenated group or a heterocyclic group of the formula (aa), (bb) or (cc) is optionally treated with one or two keto groups (=〇), 〇H, Ci 2 alkoxy, ci 2 fluoro group Substituted with alkoxy (eg, trifluoromethoxy) or Cl-2 alkyl; and wherein any 0H, alkoxy or fluoroalkoxy substituent is not attached (bonded) to formula (I) The R3 ring carbon of the -NH- group is substituted and is not substituted at any R3 ring carbon bonded to the Y group of the heterocyclic group diagram (aa), (bb) or (cc). Alternatively or additionally to the definition of R3 selected above, in an alternative embodiment of the invention, X is NR4R5 or 0R5a, wherein: R4 is a hydrogen atom (H); Cle6 alkyl; Cu fluoroalkyl Or a C2-6 alkyl group, substituted by a substituent R11; and R5 is a hydrogen atom (H); an alkyl group; a fluoroalkyl group; a l-2 alkyl-substituted C3.8 cycloalkyl group; or a _(CH2)n4-C3.8 cycloalkyl group, optionally in the -(CH2)n4-shornyl group or in the c3-8 ring group In the group, by the q 2 _2 alkyl group 87841_96 〇 3 〇 3 _ .doc -25 - 1283678 generation, wherein η4 is 1, 2 or 3; or R5 is C2-6 alkyl, by one or two independent substituents Rii substituted; wherein each substituent R11, irrespective of any other Rii substituent present, is: hydroxy (OH); CV6 alkoxy; phenyloxy; benzyloxy; -NR12R13; -NR15-C(0 R16; -NR15-C(0)-0-R16; -NR15-C(0)-NH-R15; or -NR15-S〇2R16; and any R11 substituent thereof, which is 0H, alkoxy Or -NR12R13, which is not substituted at any carbon atom of any R4 or R5 substituted alkyl group which is bonded to the nitrogen of NR4 R5; or R5 is -(CH2)n"-C(0)R16;(CH2)n12-C(0)NR12R"; -CHR19. C(0)NR12 R13 ; -(CH2 )n 12 -C^OR16 ; -CHR19 -^(Ο)ΟΚ1 6 ; -(CH2 )n 12 S 〇2-NR12R13 ; -(CHdnU-SC^RM ; or _(CH2)ni2-CN; where nll is 〇, 1, 2, 3 or 4, and n12 is 1, 2, 3 or 4; or R5 is - (CH2)ni3_Het 'where nu is 〇, 1, 2, 3 or 4, And this is a 5-, 6- or 7-membered saturated or partially saturated heterocyclic ring containing one or two ring heteroatoms independently selected from the group consisting of ruthenium, S and iridium; any ring hetero atom present therein, when y3 is At 1 o'clock, it does not bind to the 2)/3^ group, and when nU is 〇, it does not bind to the nitrogen of NR4R5; where it is present and not unsaturated (meaning it does not participate in the double bond) Any ring nitrogen is present as NR17 wherein Rw is as defined herein; and wherein one or two carbon ring atoms are independently substituted by C12 alkyl as appropriate; or R5 is phenyl, optionally one or two of the following groups Group substitution: a halogen atom; a C1M alkyl group (e.g., an alkyl group); a Cl. 2 fluoroalkyl group (e.g., a trifluoromethyl group c alkoxy group (e.g., Cl-2 alkoxy group); a C 2 fluoro group alkoxy group (e.g. ^甲^基); CW complete base (Cl_2 base.s〇2_); Ci 2^_sn R7R«N-S02- ; R7R3N-CO-; -NR15-C(0)R16 ; r7rsn; h; Ci 87841-960303-中.doc -26 - 1283678 oxymethyl; A·4 alkoxyethyl; Cl-2 alkyl _s〇2_CH2_; cyano (CN); or phenyl, as appropriate By one or two fluoro, chloro, Cij alkyl, Ci fluoroalkyl, Q-2 alkoxy or ^ Alkenyloxy substituted; wherein R7 and R8 are independently a hydrogen atom (H); Cl_4 alkyl (eg, Cl-2 alkyl, such as methyl); C3_6 cycloalkyl; or phenyl, optionally one or two Substituted by the following groups: fluoro, chloro, Cl 2 alkyl, (fluoroalkyl, Ci-2 alkoxy or Q fluoroalkyloxy; or R7 together with R8 is _(CH2)n6- or _ c(〇)_(CH2)n7· or -C(0)-(CH2)n 7 -c(0)· or -(CH2 )n 8 -X7 -(CH2 )n 9 -or-c(0) -x7 - (called ^, where: n6 is 3, 4, 5 or 6, n7 is 2, 3, 4 or 5 (n7 is preferably 2, 3 or 4), η8 and η9 and ηι〇 are independent 2 Or 3, and χ7 is 〇 or wherein R14 is Η or C!-2 alkyl; or R5 has the formula (8), (y) or (z):

And in which in the subtype (8) 'n=M2; in the subtype (y), m=1 or 2; in the subtype (z), r = 〇, i or 2; wherein in the subtype (X) (y), among the A, B, D, E & F, none or one or the rain is nitrogen, and the remaining A, B, D, E and F are independently CH or CR6; wherein R is _ atom; Cw Alkyl (e.g., Cm alkyl); Cw fluoroalkyl (e.g., 4·2 fluoroalkyl); Cl_4 alkoxy (e.g., q. 2 alkoxy); fluoroalkoxy·'c>-2 alkyl Sulfhydryl (Ci-2 alkyl _s〇2-); alkyl name 〇 factory __ ; R7R8N-so2.; r^r«n-co-; -NR^-C(0)R16 ; r7R8N; Oh; Ci oxymethyl, cw alkoxyethyl; Ci_2 alkyl _s〇2_CH2_; cyano (CN); 87841·96〇3〇3_中.d〇c -27- 1283678 or phenyl, depending The condition is substituted by one or two fluoro, chloro, Ci 2 alkyl, q fluoroindolyl, Ck alkoxy or cardinyl fluoroalkoxy; wherein both hydrazine and hydrazine are as defined herein; Wherein G is 0 or S or NR9, wherein r9 is a hydrogen atom (8), a Ci-4 alkyl group or a Ch fluoroalkyl group; and none of J, L, Μ and Q is one or one L ^^4 three Nitrogen; while the remaining J, L, Μ and Q are independently CH or CR6, of which R6 As defined herein; or R4 and R5 are taken as -(CHJp1· or -C(〇HCH2)p2_ or -(αΪ2)ρ3_χ5_(CH2)p4- or -C(0>X5_(CH2)p5_, where: Pl = 3, 4, 5 or 6 (preferably P = 4 or 5), P2 is 2, 3, 4 or 5 (p2 is preferably 2, 3 or 4), and p3 is independent of ?4 and P5 2 or 3 (preferably independently 2), and X5 is 〇 or NR1 7 ; wherein R17 is a hydrogen atom (H); C! · 4 alkyl (for example, Q j alkyl); q · 2 fluoroalkyl; C3 -6 cycloalkyl; -(CH2)p6-C(0)R16, wherein ρ6 is 〇, i, 2 or 3 (p6 is preferably 0); -(CH2)p6-C(0)NR12R13; -( CH2)p6-C(0)〇Ri6; -S〇2 R1 6 ; or phenyl or benzyl, wherein the phenyl or benzyl group is optionally substituted with one or two of the following groups at the aromatic carbon atom: a tooth atom, a Cl-2 alkyl group, a Ci fluoroalkyl group, a Cij alkoxy group or a heart fluoroalkoxy group; and wherein R4 and R5 are taken together as -(CHJp1- or -C(0)-(CH2) When p2-, the NR4R5 heterocyclic ring is optionally substituted by a Ris substituent, wherein Ris is: Ci 4 alkyl (for example (V2 alkyl); Cm fluoroalkyl; C3-6 cycloalkyl; CV2 alkoxy ( Not substituted at the NR4R5 ring-nitrogen ring-carbon; Cl fluoroalkoxy a group (not substituted at the ring to the ring of NR4R5 ring-nitrogen-carbon); 〇H (not substituted at the ring-carbon bonded to NR4R5 ring-nitrogen); -(CH2)p7_c(9)Ri 6, where p7 is 〇 1, 2 or 3 (p7 is preferably 〇 or 1); -(CH2)p7-C(0)0R16; -(CH2)p7- 87841·96〇3〇3·中.doc -28 - 1283678 OC ^R1 6 ; -(CH2 )p 7 -C(0)NR12 R13 ; -(CH2 )p 7 -NR15 C(0)R!6 ; -(CH2)P7-NR15C(0)NR12R13 ; -(CH2) p7-NR15C(0)0R16; .(CH2)p7·so2r16; -(CH2)p7.S02NR12R13; -(CH2)p7-NR15S02R16; -(CH2)p7-OH; -(CH2)p7-OR1 6 ; Or phenyl, optionally substituted by one or two of the following groups: _Atom, C^2 alkyl, C! fluoroalkyl, Q-2 alkoxy or (^fluoroalkoxy; or R4 and R5 - used as _(CH2)pl- or <(〇)_(CH2)p2- or _(CH2)p3-X5-(CH2)p4- or -(:(0)-Χ5_ as defined herein ((:Η2)ρ5·, and wherein the NR4R5 heterocyclic ring is fused to the benzene ring, optionally substituted with one or two of the following groups on the phenyl group: a halogen atom, a Ci-2 alkyl group, a (fluoroalkyl group) , (^-2 alkoxy or (^ fluoroalkylalkoxy; and R is Cl. 8 fluorene-based 'Cl-8 fluoroalkyl; C3-8 ring Phenyl group, optionally substituted with one or two of the following groups: _ atom, cl-2 alkyl, trifluoromethyl, Cl _2 succinyl or trifluoromethoxy; or R5 a has a definition as defined herein Sub-formula (8), (y) or (z) and wherein: R12 and R13 are independently H; Cu alkyl (eg c-3 alkyl); C3_6 cycloalkyl; or phenyl, optionally one or two Substituted by a halogen atom, a Ci-2 alkyl group, a Ci fluoroalkyl group, a q-2 alkoxy group or a heart fluoroalkoxy group; or R12 together with Ri3 is -(αΐ2)Λ or -C(〇&gt ;(CH2)n7_ or _c(〇)_(CH2)n7·C(o)- or -(ch2)n 8-χΐ 2 _(Ch2 )n 9 or _c(0>xl 2-(Ch2 ) Ni 〇... where n6 is 3, 4, 5 or 6 (n6 is preferably 4 or 5), n7 is 2, 3' 4 or 5 (n7 is preferably 2, 3 or 4), η8 and η9 and Ηι〇 is independently 2 or 3 (preferably independently 2), and X12 is 0 or NR14, wherein RM is η or Cl-2 alkyl; 87841-96〇3〇3·中.doc -29- 1283678

Rl 5 is a hydrogen atom (Η); Ci -4 alkyl (such as tBu or q · 2 alkyl, such as methyl); C 3 -6 cycloalkyl; or phenyl, optionally with one or two of the following groups Substituted: from atom, C1-2 alkyl, Ci fluoroalkyl, Ci-2 alkoxy or (^fluoroalkoxy; Han cle4 alkyl (eg C!-2 alkyl); C3_6 cycloalkyl Or a phenyl group, or a phenyl group, optionally substituted with one or two of the following base diagrams: a halogen atom, a C 2 alkyl group, a Ci fluoroalkyl group, a Q 2 alkoxy group or (^fluoroalkoxy; and Rl9 is cw alkyl; -(CH2)n20-OR20, wherein η20 is 1, 2, 3 or 4, and R is a hydrogen atom (Η) or a Ch alkyl group; Η(]ν^)-ΟΗ; -CH2-SH; -CH2-CH2-; benzyl; or (4-hydroxyphenyl)methyl (ie 4-hydroxy-yl). In compounds, for example The alkyl group or partial group of the formula (I) (or formula (IA) or formula (IB), as described later) may be linear or branched. The alkyl group which may be employed, for example Cl-s alkyl or Ci.6 alkyl or Ci4 alkyl or alkyl or ^2 alkyl 'includes Ci0 alkyl or Ci4 alkyl or Ci3 alkyl or alkane $ such as methyl, ethyl, -propyl, n-butyl, n-pentyl or n-hexyl or any of its branched isomers, such as isopropyl, tert-butyl, terpene, butyl, 3-methylbutyl -2_yl, 2-ethylbutan-1-yl or the like is intended to be targeted,

Alkoxy", "alkylene," and derived from alkyl or Ci. 2 alkoxy, packaged

Other bases of sulfonyl sulfhydryl (decanesulfonyl) and acetaminophen. For example, Ci.6 alkoxy or alkoxyl, ethoxy, propoxy, and the above-listed sulphur-based thiol groups, such as 4-4, ), ethyl oxime and derived from the above alkyl sulfonyloxy group, such as (^-4 alkylsulfonyloxy 87481-960303-中.doc 1283678 base, including methanesulfonyloxy ( Methanesulfonyloxy), ethanesulfonyloxy, etc. πcycloalkyl", for example c: 3-8 cycloalkyl, including cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl , cyclooctyl, etc. The C3-8 cycloalkyl group is preferably a c3-6 cycloalkyl group or a C: 5·6 cycloalkyl group, which contains a 3-6 member or a 5-6 membered carbocyclic ring. Included are alkyl groups having one, two, three, four, five or more fluorine substituents, such as fluoroalkyl or fluoroalkyl or Ci 2 fluoroalkyl, such as monofluoromethyl, difluoromethyl, tri Fluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl (CF3CH2-), 2,2-difluoroethyl (CHF2CH2-), 2-fluoroethyl (CH2FCH2-), etc. "Fluoroalkoxy" includes C^4 fluoroalkoxy or c1-2 fluoroalkoxy, such as trifluoromethoxy, pentafluoroethoxy, Fluoromethoxy, difluoromethoxy, etc. "fluoroalkylsulfonyl", such as (^_4 fluoroalkylsulfonyl, including trifluorosulfonate fluorenyl, pentafluoroethyl fluorenyl The self-atoms ("dentate groups") present in the compound, for example, in the compounds of formula 1, may be fluorine, chlorine, bromine or iodine atoms ("fluoro-based", "chloro-based", "bromo-based, , or "iodo". When this patent specification states that the original or part of the group A "combines" or ",", connects to an atom or a part of a group B, it means an atom / part The group A is usually bonded directly to the atom/partial group B by means of one or more covalent bonds, and the A system is indirectly linked to B via one or more intermediate atoms/partial groups (eg excluding ACB) Unless otherwise expressly intended to contain another meaning, R1 is preferably _4 alkyl (eg methyl, ethyl, n-propyl, isopropyl or n-butyl), hydrazine: 1-3 fluorocarbon Or -〇12(:112〇11;111 is more preferably (::1_3 alkyl (such as methyl, ethyl or n-propyl), Cl-2 fluoroalkyl or -Ch2CH2〇h; yet more 87841 -960303-中.doc -31- 12836 78 is preferably a Ci -3 group, a C 2 gas group or a -CH 2 CH 2 OH group such as a mercapto group, an ethyl group, a n-propyl group or a -CH 2 CH 2 〇H. R 1 is more preferably a c 2 _ 3 alkyl group (for example, ethyl or N-propyl), fluoroalkyl (eg q fluoroalkyl-CH2-, such as CF3-CH2-) or -CH2CH2〇H; especially ethyl, n-propyl or _CH2cH2〇H. R1 is most preferably ethyl. R2 is preferably a hydrogen atom (H) or a methyl group, more preferably a hydrogen atom (H). In R3, it is preferred to have one substituent or no substituent. In a preferred embodiment, R3 is optionally substituted C3 cycloalkyl or an optionally substituted heterocyclic group of the formula (aa), (bb) or (cc). In this particular embodiment, as the case may be, in R3, a heterocyclic group of C3-8 cycloalkyl or subtype (aa), (bb) or (cc) is optionally one or two Substituted by a substituent, the substituent is independently (for example) a keto group (==〇), 〇H, a Ci 2 alkoxy group, a Ci 2 fluoro-based ke group (for example, a difluoromethoxy group) or a q 2 alkyl group. And any of the OH, alkoxy or fluoroalkyl alkoxy substituents are not substituted at the R3 ring carbon attached (bonded) to the formula 1_NH- group, and are not bonded to the heterocyclic group Any one of the R 3 ring carbons of the Y base ring of (aa), (bb) or (d) is substituted. In a preferred embodiment, wherein R3 is optionally substituted C3i cycloalkyl, which is not optionally substituted Cs cycloalkyl, meaning that it is not optionally substituted cyclopentyl. In this case, ruthenium is preferably a C6 -8 ring group which is optionally substituted. In the case where R3 is an optionally substituted A.8 cycloalkyl group, it is more preferably an optionally substituted A cycloalkyl group (ie, cyclohexyl group); for example, a Q cycloalkyl group, as the case may be one or two Substituted by a substituent, the substituent is independently (for example, ketone group (=0), OH, C 2 alkoxy, C 2 alkoxy (for example, trifluoromethoxy) 87841-960303· .doc -32- 1283678 or 4-2 alkyl, and any of the 0H, alkoxy or fluoroalkoxy substituents are not attached (bonded) to the R3 ring carbon of the formula (1) -NH- group Replaced by. In the case where R3 is an optionally substituted C^8 cycloalkyl group, one or two of the optional substituents preferably include (for example, whether or independently (as if it is a "keto group H)); OH; Cl Alkoxy; Cl fluoroalkoxy (e.g., trifluoromethoxy); NHR21, wherein R21 is a hydrogen atom (HhiLCM linear alkyl; Ci2 alkyl, such as methyl 'C! fluoroalkyl, such as _Cjj2f Or _CHp2; _CH2〇H; -CH2NHR22, wherein R22 is H; _c(〇)〇R23, wherein R23 is Η or methyl; • C(0)NHR24, wherein R24 is Η or methyl; _c(〇) R25, wherein r25 is methyl; fluoro; hydroxyimino (=N-OH); or (cle2 alkoxy)imide (=N_OR2 6, wherein r2 6 is Ci 2 alkyl); Any hydrazine H, alkoxy, fluoroalkoxy or NHR21 substituent will not be substituted at the R3 ring carbon attached (bonded) to the group of formula 1, and will not be bonded to the heterocyclic group (aa) Any one of the Y groups of the Y group of (bb) or (cc) is substituted with a R3 ring carbon. More preferably, in the case where R3 is optionally substituted c>8 cycloalkyl, one or two optional substitutions The base system includes (for example, is or is independent (for example, for) Keto group (=0); OH; NHR21, wherein is a hydrogen atom (8); Ci 2 alkyl, such as methyl; q fluoroalkyl, such as -CI^F or -CHF2; _C(0)0R23, wherein R23 is H Or methyl; -C(0)NHR24, wherein r24 is H or methyl; fluoro; hydroxyimino (=乂0Η); or (Cu alkoxy)imide (=N_OR26, wherein 2 alkyl More preferably, in the case where R3 is optionally substituted (: 3-8 cycloalkyl), one or two selected substituents include (for example, are or independently (for example)) a keto group. (=0) ; OH ; NHR21, wherein r 2 1 is a hydrogen atom (H); methyl b; _CHF 2 b C(0) 0R23 'where R 23 is η; a fluoro group; a hydroxyimino group (Ta 〇 11); 87841 -960303-中.doc -33- 1283678 or ((V2 alkoxy)imino (=n_OR26, wherein R26 is Ci_2 alkyl). Still more preferably in R3 is optionally substituted q.8 ring In the case of an alkyl group, one or two optional substituents include (for example, are or independently (for example)) a keto group (=0); 0H; a methyl group; a fluoro group; a hydroxyimino group (=N) _〇H); or (Cl? alkoxy)imido group (=N-OR26, wherein R26 is c1-2 alkyl). The best is in the case of R3 In the case of a substituted A.8 cycloalkyl group, one or two of the optional substituents include (for example, or independently (for example)) 0H, keto (=〇) or sulfhydryl (=n-〇) h). For example, one or two alternative substituents can include, for example, 〇H and/or keto groups (=0). Depending on the sinking, in R3, the A-8 cycloalkyl group can be unsubstituted. In the case where R3 is optionally substituted A-8 cycloalkyl, for example, optionally substituted A-8 cycloalkyl, such as optionally substituted C6 cycloalkyl (optionally substituted cyclohexyl) One or two optional substituents, if present, preferably include a substituent at the 3-, 4- or 5-position of the R3 cycloalkyl ring (e.g., one or more substituents). (In this connection, the μ position of the R3 cycloalkyl ring is regarded as the point of attachment to -ΝΗ- in the formula (I). In the case where R3 is optionally substituted C:3·8 cycloalkyl, any oxime, alkoxy, fluoroalkoxy, —ch2oh, —ch2ch2oh, —ch2nhr22, _〇Χ〇ρκ23 > C(0)NHR24, -C(0)R25 or a fluoro substituent (particularly any OH substituent) is more preferably at the 4 or 5 position of the R3 cycloalkyl (eg C6 8 cycloalkyl) ring, For example, at the 3- or 5-position. For example, any hydrazine H, alkoxy, fluoroalkyl alkoxy, -CH20H, -CH2CH2OH, -CH2NHR22, _CX〇X)K23, _C(0)NHR24, -C(0)R25 or a fluoro substituent (specific Is any OH substituent), may be in the 3-position of the R3Cs cycloalkyl (cyclopentyl) ring, or in 87841-960303-.doc -34- 1283678 Han C6 $ clothing ^ yuan base (cyclohexyl) soil 3_, 4- or 5-position, for example 3- or 5-position (as far as this and below is concerned, the 1-position of the R3 ring-based ring is considered to be the connection of -NH- in formula (I) point). In the case where R is optionally substituted C3-8 cycloalkyl, any npjr2 1 substituent is preferably 2-, 3-, 4 in the R3 cycloalkyl (eg, C0-8 cycloalkyl, eg cyclohexyl) ring. In the - or 5-position, preferably a 2- or 3-position, or more preferably a 3_ position. In the case where R3 is optionally substituted A-8 cycloalkyl, any alkyl or fluoroalkyl substituent is preferably attached to the R3 cycloalkyl (eg, C6-8 cycloalkyl, eg cyclohexyl) ring. In the -, 2-, 3-, 4- or 5-position, more preferably a 1-, 2-, 3- or 5-position, and still more preferably a 1- or 3-position. In the case where R3 is optionally substituted C3-8 cycloalkyl, any keto (=0), hydroxyimino (=N-OH) or _4 alkoxy) imine (=N) The -OR26) substituent is preferably at the 3- or 4-position of the R3 cycloalkyl (e.g., C6-8 cycloalkyl, e.g., cyclohexyl) ring, preferably at the 4-position. In the case where R3 is an optionally substituted C3_8 cycloalkyl group, R3 is preferably a cyclohexyl group (ie, unsubstituted), or a keto group (=〇), 〇H, NHR21, q _2 alkyl group, (V2 fluoroalkyl, -CH20H, -C(0)0R23, -C(0)NHR24, _C(0)R25, fluoro, hydroxyimino (=N-〇H), (Ch alkoxy) a cyclohexyl group substituted with an imido group (=N-OR26), or a cyclohexyl group substituted with two fluoro substituents. R3 is more preferably a cyclohexyl group (ie, unsubstituted), or a keto group (= 9. OH, NHR21, Cu alkyl, Cu fluoroalkyl, -C(0)OR23, fluoro, hydroxyimino (=N-0H) or (Ch alkoxy)imide (=N-OR26 a cyclohexyl group substituted with a substituent or a cyclohexyl group substituted with two fluoro substituents. R3 is more preferably a cyclohexyl group (ie, unsubstituted), or a keto group (=〇), hydroxyimine 87841 -960303-中.doc -35- 1283678 (=N-OH), C! _2 alkyl or OH substituent substituted cyclohexyl. The substituent may be selected at the 3- or 4-position of the R3 cyclohexyl ring, For example, 3-position; more preferably any OH substituent is preferably at the 3-position of the R3 cyclohexyl ring, and/or any keto group =0), hydroxyimino (=N-OH) or (C!-4 alkoxy)imido (=:N-OR26) The substituent is preferably at the 4-position of the R3 cyclohexyl ring. In the case where R3 is an optionally substituted C6 cycloalkyl group, R3 may be, for example, a 4-methyl-cyclohexyl group (that is, a 4-cyclohexyl-1-yl group), but R3 is more preferably a cyclohexyl group ( That is, unsubstituted), 3-hydroxy-cyclohexyl (ie 3-hydroxycyclohexane-1-yl), 4-keto-cyclohexyl (meaning 4-ketocyclohexan-1-yl) , 4-(imido)cyclohexyl (ie 4-(imido)cyclohex-1-yl), 4-((^-2 alkoxyimino)cyclohexyl, 1-methyl Cyclohexyl or 3-methylcyclohexyl. When R3 is optionally substituted by a C6 cycloalkyl group, 'R3 is preferably cyclohexyl (ie unsubstituted), 4-keto-cyclohexyl (meaning That is, 4-ketocyclohexan-1-yl) or 4-(hydroxyimino)cyclohexyl (ie, 4-(hydroxyimino)cyclohexyl). In R3, C5 is optionally substituted. The cycloalkyl group (optionally substituted cyclopentyl group) can be, for example, a % pentyl group (ie, unsubstituted) or a benzyl-cyclopentyl group. In the case of saturating <:5_7 ring-bonding group, it is preferably an early-unsaturated-C5 -6 ring-bonding group which is substituted depending on the condition, and more preferably a monounsaturated-C0 ring fluorenyl group which may be optionally substituted. (Immediately substituted monounsaturated cyclohexenyl = optionally substituted cyclohexenyl). R3 cyclohexenyl is more preferably a cyclohex-3-enyl group which is optionally substituted. In the case where R3 is a monounsaturated _C5_7 cycloalkyl group substituted by the apparent sinking, the R3 cyclodecyl group is preferably taken by one or two substituents of a fluoro group or a methyl group as 87841-% 〇3〇. 3-中.doc -36- 1283678, provided that if there are two substituents, they must not be methyl. The R3 cyclodecyl group is preferably substituted by a substituent of a fluoro group or a -2 alkyl group (e.g., methyl group); the R3 ring group is more preferably substituted by a fluoro group substituent or unsubstituted. For the R3 cyclodecyl group, the substituent may be selected at the 1-, 2-, 3-, 4- or 5-position of the cycloalkyl ring. In the case where R3 is a heterocyclic group of the formula (aa), (bb) or (cc), γ is preferably 0, S, S〇2, NH or NC(O)methyl, more preferably It is preferably an anthracene, NH or N.C(0)methyl group, more preferably an anthracene or an NC(O)methyl group. (When 丫 is ^ or N-C(O)methyl, RM is Η or C(0) methyl). R 0 is preferably a gas atom (H), a methyl group, an ethyl group, a c(0)NH2, a C(0) methyl group or a C(0)-CF3 group. R1 0 may be hydrogen atom (η), methyl group, ethyl group, c(q) methyl group or C(0)_CF3, more preferably Η, C(0) methyl or C(0)-CF3, and More preferably Η or c(o) methyl. In the case where R3 is a heterocyclic ring of subtype (aa), (bb) or (cc), then R3 is preferably subtype (aa) or (bb), more preferably subtype (bb). A heterocyclic group. In the subtype (bb), ηι is preferably i. In the subtype (ce), # is preferably i. That is, it is preferably a six-membered ring in the R3 heterocyclic group. In R3, the heterocyclic group of the formula (aa), (bb) or (cc) is suitably unsubstituted (in this case, in the case where γ is Nrm, R1〇 is not classified as a substitution. base). In the subunit (aa), (bb) or (CC) < R3 heterocyclic group, one or two of the optional substituents preferably include (for example, or are independently ((for example))) 〇 h; net group (=〇); (V2 alkyl (such as methyl) or fluorene 12 fluoroalkyl (such as, for example, -CH2 F or T2). R3 heterocyclic ring in subtype (4), (bb) or (d)基困8784 卜96〇3〇3_中.doc -37- 1283678 More preferably one or two substituents on the atom include (for example, or independently (for example)) OH and/or ketone groups One or two of the preferred tethers (for example) are keto groups (=Q). In the R3 heterocyclic group of the subtype ((4), (4)) or ((3)), any keto group (= Preferably, the substituent is bonded to the carbon adjacent to X and/or may be at the 2-, 3-, 4- or 5-position of the R3 heterocycle. (In this case, the position of the R3 heterocycle It is regarded as the point of attachment in Formula 1. When R3 is a heterocyclic group of the formula (aa), and γ is nrI 〇, it is preferred that R10 is not C(〇)-Me. More preferably, when r3 is a subgroup (aa) heterocyclic group and Y is NR10, then Ri 〇 is preferably not c(〇)R. That is, or for example, Rl is preferably not C(〇)NH2, CXOK: 2 alkyl or (:(0)% fluoroalkyl. In a specific embodiment, when R3 is subtype (aa) In the case of a heterocyclic group, γ is 〇, S, s〇2 or NH 〇

As the case may be, according to a particular embodiment of the invention, _皮3 is not HN. More preferably, when R3 is a heterocyclic group of the formula (bb), and Y is NR1G, and if the case is i, it is preferred that the ruler (1) is not a methyl group. More preferably, when R3 is a heterocyclic group of the formula (bb), and ¥ is 1 〇, and optionally η1 is 1, the preferred Ri 〇 is not alkyl or substituted. Alkyl, meaning or or, for example, R10 is preferably not a ClM alkyl group (e.g., methyl or ethyl), q2 fluoroalkyl or CH2C(0)NH2. In a specific embodiment, when R3 is a heterocyclic group of the formula (bb), 'γ is preferably 〇, s, s〇2 or NR", wherein Ri〇 is Η, C(0)NH2 , C (〇KV2 alkyl or c(0)_Cl fluoroalkyl, or more preferably Y is hydrazine or C(0)Me. For the subtype (bb), more preferably γ is 〇 or NR1 G. At R3 In the case of a bicyclic group of the formula (dd) or (ee), it is preferably 87841-960303-medium doc -38 - 1283678 is a subtype (ee). In the subtype (ee), Jiayu 1, Y2 and Y3 are both CH2. In other cases, NHR3 is subtypes (a), (al), (b), (c), (cl), (c2), (c3), (c4). ), (c5)5 (c6)5 (c7)5 (d)5 (e)5 (f)5 (g)? (gl)? (g2)? (g3)? (g4)? (h)5 (i) 5 〇, (k)5 (kl)5 (L), (m), (ml), (m2), (m3), (m4), (m5), (8), (〇), (〇 1), (〇2), (〇3), (〇4), (〇5), (p), (pl), (p2), (p3), (p4), (p5), (p6) , (p7), (p8) or (q):

(d) (e)

(f)

ΗΝΰ (9)

(k) (k1) (L)

HN

HN (h) (i) (1)

(m) (m2)

HN

(n) NH0

<V0H r^vNHz ilN^^ HN^ (P) (P1) (P2)

(P3) (p4) 87841-960303-中.doc -39- 1283678

In the above sub-formulas (a) to (q) and the like, the NHR3 group is delineated to the -NH-attachment point of the pyrazolopyridine 4-position of the formula (I). Preferably, NHR3 is subtypes (C), (cl), (C2), (C3), (C4), (C5), (C6), (C7), (d), (e), (f), (gl), (g4), (8), (i), 1, (k), (kl), (L), (m), (ml), (m2), (m3), (m5), (8), (〇), (〇1), (〇2), (〇3), (〇4), (〇5), (p), (P2), (P3), (P5), (P6), ( P7) or (q). More preferably, NHR3 is subtypes (c), (cl), (c4), (c5), (8), (1), 1, (k), (ml), (m2), (8), (8), (〇2), ( 〇3), (P2), (p5), (p6) or (q). More preferably NHR3 is subtype (c), (h), (k), (8), (o) or (〇2); for example (c), (h), (o) or (〇2). The most preferred R3 is tetrahydro-2-indole-piperidin-4-yl; that is, NHR3 is most preferably sub-formula (h) as shown above. According to a specific embodiment, NHR3 is subtypes (a), (b), (c), (d), (e), 1, (g), (gl), (g2), (g3), ( h), (1), 1, (k), (L), (m), (ml), (6), (〇), (〇1), (p) or (q). In this embodiment, preferably NHR3 is subtypes (c), (d), (4), (f), (gl), (h), (i), G), (k), (m), (ml), (n), (〇), (〇1), (p) or (q); and in this embodiment, NHR3 is more preferably sub-formula (c), (h), (i) , G), (k), (ml), (8), (ο) or (q). In this embodiment, NHR3 is more preferably subtype (c), (h), (k), (η) or (〇). The most preferred R3 is tetrahydro-2H-piperidin; meaning that NHR3 is most preferably subtype (h) as shown above. According to another specific embodiment, NHR3 is subtypes (a), (b), (c), (4), (4), 87841-96〇3〇3_. doc -40-1283678 (f), (g), (h), (〇, 1 or (k). In this particular embodiment, NHR3 is preferably subtypes (c), (d), (e), (f), (8), (i), 1 or (k); and in this particular embodiment, NHR3 is more preferably subtype (c), (h), (1), 1 or (k). The most preferred R3 is tetrahydro-2H-pyran-4-yl; That is, NHR3 is preferably subtype (h), as shown above. Preferably, X is NR4R5. In the case where oxime is a heart-alkyl group, it is preferably a C 4 alkyl group or a (alkyl group). In the case where 圮 is a fluoroalkyl group, it is preferably a Cl-2 fluoroalkyl group. R4 is preferably a hydrogen atom (H). In the case where R4 is a C2_6 alkyl group substituted by a substituent R11, R4 is preferably a C2-4 alkyl group substituted by a substituent R11 (e.g., C2_3 alkyl). R4 is more preferably -(CH2)n3-Rn, wherein η3 is 2, 3 or 4. More preferably, , η3 is 2 and/or R4 is -(CH2)n3-〇H. When R5 is 〇2-6 alkyl substituted by one or two independent substituents R11, R5 is preferably one or two independent Substituent R a C2-4 alkyl group substituted by i 1 (for example, C2-3 alkyl). When R 5 is a C 2-6 alkyl group substituted by one or two independent substituents RU (for example, A·4 alkyl or C 2·3 alkyl) When R5 is preferably a C2.6 alkyl group substituted by a substituent ri 1 (for example, (: 2·4 alkyl or C2-3 alkyl). R5 is more preferably _(CH2)n5_R11, wherein η5 Is 2, 3 or 4. η5 is preferably 2 or 3, more preferably 2. Each substituent R11 is independently of any other R11 substituent present, preferably: via (OH); Cm alkoxy ( For example, Ci. 4 alkoxy, such as tri-butyloxy, ethoxy or methoxy); phenyloxy; benzyloxy; eNRi2Ri3; -NR15-(:(0)1116; -NR15 - CXCO-NH-R15; or -NRi 5 _s〇2 R16 (more preferably Cm alkoxy, -NR15-C(0)-NH-R15 or -NRi5_s〇2Ri6; best _^15_ S〇2R16) In all cases, any R" substituent, which is 〇H, burn 87841-960303-medium.doc-4121283678 oxy or -NR12R13, will not be substituted at any R4 or R5 alkyl group Any carbon atom bonded to the nitrogen of NR4R5 is substituted. In the case of an alkyl group, it is preferably a Cl.5 alkyl group or an alkyl group. In the case of Ci_8 fluoroalkyl group, it is preferably a Cl.3 fluoroalkyl group or a Ci-2 gas group. In the case where R is a C3-8 cycloalkyl group optionally substituted by Ci-2, the C:3·8 cycloalkyl group is preferably not substituted at the ring-carbon attached to the NR4R5 nitrogen. . In the case where R5 is an optionally substituted C3_8 cycloalkyl group, it is more preferably a C3-8 cycloalkyl group (i.e., unsubstituted). When R5 is optionally substituted -(CH2)n4-C3_8 cycloalkyl, wherein n4 is 1, 2 or 3, then η4 is preferably 1 or 2, or more preferably 1, and/or R5 is preferred. The -(CH2)n4-C5_6 ring group or the optionally substituted -(CH;2)n 4 -C6 cycloalkyl group is optionally substituted. When R5 is optionally substituted _(CH2)n 4 -C3 -8 cycloalkyl, it is preferably unsubstituted. R5 is most preferably (cyclohexyl)methyl-, meaning -CH2-cyclohexyl. When the ruler is a heart-4 alkyl group, it is preferably an isobutyl group, a second butyl group or a Cl-3 alkyl group such as a methyl group or an isopropyl group. When R19 is -(CH2)n2G-〇 When R20, it is preferably n2G is 1, and/or R2G is preferably a hydrogen atom (H). C(0)NR12R13; -(CH2)n12-C(0)0R16; -CHR19-C(0) 0R16; -(CH2)n12-S02-NR12R13; -(CH2)n12-S02R16; or -(CH2)n12-CN; then in a specific embodiment of the invention, R5 can be: _(CH2) nu-C(0)R16; -(CH2)n 12 -CCCONR12 R13 ; -(CH2 )n 12 -QOpR16 ; -(CH2)n12-S02-NR12R13 ; -(CH2)n12-S02R16 ; or -(CH2) n12-CN. When R5 is -(CH2)nn-C(0)R16; -(CH2)n12-C(0)NR12R13;-(CH2)n12· 87841-96〇3〇3-中.doc -42 - 1283678 C_R^ even) nl2-S〇2W2Rl3; even) nl2 mom RU ^ -(CH2)n12-CN# ; ^R5?T4^^.(CH2)ni,.C(〇)Rl6 . _(CH2) Ni2. C_^R"; or -(CH2)nl2-CN; preferably _(cH2)nii_c(〇)Ri6. π is preferably Bu 2, 3 or 4; n11 is more preferably.... advantageously For i or 2 m when m(CH2)n"_Het, nu is preferably 〇, _, and more preferably _.

Het is preferably a 5- or 6-membered saturated or partially saturated heterocyclic ring, and/or is preferably a 4-, 5-, 6- or 7-membered saturated heterocyclic ring. The heterocyclic Het preferably contains a ring hetero atom selected from the group consisting of ruthenium, 8 and N. The carbon ring atom in Het is preferably unsubstituted. This is best for one of the following:

When R5 is optionally substituted phenyl, it is preferably a phenyl group optionally substituted with one or two substituents as defined herein. When R5 is optionally substituted phenyl, then R5 is preferably a phenyl group optionally substituted by one, two or three (preferably one or two; or one) of the following groups: Preferred is a fluoro group and/or a gas group; a Ci2 alkyl group; a Ci2' alkyl group (e.g., a trifluoromethyl group); a Q2 alkoxy group (e.g., a methoxy group); a trifluoromethoxy group; Sulfhydryl (Cu alkyl-so2_); cle2 alkyl-S02-NH-; R7R8N-S02-; R7r8n-CO-; -NR15-C(0)R16; ;〇H; c卜2 alkoxymethyl ; C1-2 alkyl-S〇2-CH2_; cyano (CN); or phenyl, optionally as a fluorine group, C!·2 alkyl group, q fluoroalkyl group, Ck alkoxy group or 〇1 fluoro group One of the alkoxy 87841-96〇3〇3-中.doc-43- 1283678 is substituted. R5 is more preferably a phenyl group which is optionally substituted with two or more (preferably one) of the following groups: a ruthenium atom, a Cl 2 alkyl group, a trifluoromethyl group, a Ci 2 alkoxy group, a trifluoromethoxy group. , r7r8n-S〇2_, R7RSN_c〇_ or Ci 2 alkyl_s〇2_CH2_❶ When R5 is optionally substituted phenyl, it is preferred that one or both of the substituents are attached to benzene The _(3_ and/or 5_) and/or the _(4·) positions between the rings are substituted with respect to the benzene ring-carbon bonded to the 尺5 nitrogen. R7 and/or R8 are preferably independently a hydrogen atom (8); q _2 alkyl, such as methyl; C: 3·6 cycloalkyl; or phenyl substituted by one of the following groups: fluoro, chloro Base, q-2 alkyl, (^fluoroalkyl, Cl-2 alkoxy or (^fluoroalkoxy; or R7 and R8 - (CH2)n6_ or _(CH2)n8-X7- (CH2)n9-, wherein X7 is NR14, or preferably 〇. When R7 is cycloalkyl or optionally substituted phenyl, then r8 is preferably neither cycloalkyl nor optionally substituted. R7 and/or R8 are preferably independently a hydrogen atom (H) or a Ci_2 alkyl group. R7 is preferably a hydrogen atom (H). η is preferably 4 or 5. η7 is preferably 2, 3 or 4. η8, η9 and/or η1 〇 are preferably independently 2. In general, R5 preferably has the subtype (X) or (7) or (yl) or (8). When R5 has the subtype (X) or ( When y) or (yl) or (8), then R5 preferably has the formula (8) or (y) or (yl) or has the formula (X) or (y) or (8). R5 preferably has the subtype (8) or (y), preferably (X). η is preferably 1 or 2. More preferably n = 1. Preferred m = 1. Preferred r = 1 or 2, more preferably 87841-960303 - medium. doc - 44 - 1283678 in the Asian style (x) (y) and/or (yi), preferably none or - or two of a, b, d, e and f are nitrogen; none of A, B, c, E*F or one or two Or three 4 CR6; and the remaining A, B, D, E and F are CH. More preferably none or one or two of BDE and F are nitrogen; none of α, β, 〇, ε and F or One or two *CR6; and the remaining A, B, D, e&f are CH. In sub-forms (8), (7) and/or (yi), preferably none or one of a, B, D, E and F is nitrogen, and/or preferably no, one or two of A, B, D, E and F are CR 6. · Subtype (8) is preferably: fluorenyl; phenethylbenzyl, which is on the phenyl ring Substituted with one or two R6 substituents; phenethyl, substituted on the phenyl ring by one or two R6 substituents; or one of the following:

Wherein R6a is R6 or (preferably) hydrogen as defined herein. The subtype (X) is most preferably benzyl or pyridylmethyl•CH2Y^i [e.g. pyridylmethylmethyl (i.e., pyridin-3-ylmethyl, -ch2, or preferably pyridin-2-) Methyl group (meaning)] 87841-96〇3〇3_中.doc -45- 1283678 Asian (y)

Good for

Wherein R6a. is or independently such that, as defined herein, / 4 is a hydrogen subtype (y) preferably does not be on the carbon between the & aromatic ring and the carbon bonded to the nr4r5 nitrogen. Keto group substitution.

Wherein or independently is R0 or preferably hydrogen as defined herein. In the subtype (Z), it is preferred that none or one or two of J, L, oxime and Q are nitrogen. In the formula (X), (force and / or (8), each R6, and any other R6 present, preferably fluorine, gas, bromine or atomic, methyl, ethyl, n-propyl, Isopropyl, Aalkyl, trifluoromethyl, _CH2〇H, methoxy, ethoxy, q-fluoroalkoxy (eg trifluoromethoxy or difluoromethoxy), 〇H, Cl - 3 alkyl S (〇) 2 - (such as methyl cross-linking, which is MeS (0) 2 -), q _ 3 alkyl 8 (〇) 2_·-, such as methyl-S02-NH- ,Me2N-S(0)2-, H2N_S(〇)2-, -CONH2, -CONHMe, -C02H, cyano (CN), NMe2, tri-butoxymethyl, or Cb3 alkyl S(0 2-CH2-, such as methyl-S02-CH2-, each, independently of any other R6 present, more preferably a fluorine, gas, bromine or iodine atom, methyl, ethyl, n-propyl, iso Propyl, isobutyl, trimethyl, 87841-960303-φ^〇〇-46 - 1283678 -CH2 OH, methoxy, ethoxy, q-fluoroalkoxy (eg trifluoromethoxy or Difluoromethoxy), C^-3 alkyl S(0)2-, such as methylsulfonyl, Ci_3 alkyl S(0)2-NIl·, such as methyl-S02-NH-, Me2N- S(0)2-, H2N-S(0)2-, _conh2, or Ci-3 The group s(o)2-ch2-, such as methyl-so2-ch2. Each R6, independently of any other R6 present, is more preferably a fluorine, chlorine or bromine atom, methyl, ethyl or n-propyl. , isopropyl, trifluoromethyl, -CH 2 OH, methoxy, difluoromethoxy, methylsulfonyl, methyl-S02-NH- or methyl-S02-CH2- ο The R6 substituent is also independently a preferred phenyl moiety and an independent substituent in the case where the phenyl group is optionally substituted at r5. In the subtypes (X) and/or (y), preferably one or two. Or three R6 substituents are present in B, D and/or E; such that, for example, in subformula (X), one, two or three R substituents are present in the intermediate _ (3- and / or 5 _) and / or in the _ (4_) position, relative to - ((: Qiao Yun side chain. In the subtype (8) and / or (y), any choice of R6 substituents may only exist in B, D and / Or E, such that in the subtype (χ), any optional r6 substituent is present only in the inter-(3- and/or 5_) and/or in the _(4_) position, relative to -(〇^)0 In the case of a side chain, or in the subtype (8), any r0 substituent may be selected, in the o-(2- and/or 6-) position i, relative to the even side For, either alone or in combination with one or more other substituent groups R6 selected and used. Overall for R5

Cl - 6 alkyl (for example, Cj, 2 or R5 is preferably a hydrogen atom field); a cycloalkyl group (for example, c5_6 cycloalkane' is optionally substituted by one or two of the following dimethyl, methoxy or trifluoro Methyl group or (:3·6 alkyl); cle4 fluoroalkyl group, (C5·6 cycloalkyl)methyl group, phenyl group substitution · fluorine or chlorine atom, methyl group, 87841·96〇 3〇3_中.doc •47-1283678 oxy; or R5 has the formula (X), (y) or (z), for example, as described above. More preferably, R5 is a hydrogen atom (H), methyl, ethyl, n-propyl, isopropyl, 2-ethylbutan-1-yl, cyclopentyl, cyclohexyl, (cyclohexyl)methyl_ An optionally substituted base such as a fluorophenyl group such as 4-fluorophenyl, optionally substituted benzyl or optionally substituted pyridylmethyl. R5 may optionally be a genomic group, p is more than a benzyl group (e.g., p is more than benzyl-4-yl fluorenyl, p is more than -3-methylmethyl, or preferably pyridin-2-ylmethyl) or 4- Fluorophenyl. NR4R5 is preferably not NH2. R5 is preferably not a hydrogen atom (H). When R4 and R5 are used together, _(CH2)p 1 _ or optionally substituted -C(0)-(CH2)p2- or -(CH2)P3-X5-(CH2)P4 Or -C(0)-X5-(CH2)p5- or any of the foregoing partially unsaturated derivatives, R4 and R5 are preferably employed together as an optionally substituted -(CHJp1- or optionally substituted _C(0)-(CH2)p 2 - or -(CH2 )p 3 -X5 -(CH2 )p 4 - or -C(9)_X5 -(CH2 )p 5 - (meaning not part of any of these Unsaturated derivatives). When R4 and R5 are used, they are substituted by Ri8 as appropriate (CHJp1-, or -C(〇HCH2)p2- or -(ch2)p3-x5-(substituted by R18) When ch2)p4-, nr4r5 may be, for example, a <3, optionally replaced by R18, or: N0, as the case may be replaced by R18, or, if appropriate, by R18, or: one (meaning r4, _r ~\ Use with R5 as -(CHA-NCR17)-((:112)2-) or :(meaning that R4 and R5 together are -(ch2)2-o-(ch2)2·). R17 Preferred is a hydrogen atom (H); a Ci-4 alkyl group (e.g., Q-2 alkyl group); a C3·6 ring pit group; -(ch2)p6-c(o)r16 or an optionally substituted phenyl group or芊 base ° R is more preferably H; (: 2 2 alkyl; - (CH2) P6-C (0) R16 or a substituted phenyl group. 87841-96〇3〇3_中 doc -48 - 1283678 When R4 and R5 are used together as an oxime or -C(〇HCH2)p2-, the nrW heterocyclic ring is preferably not R1 8 is substituted. When R4 is combined with R5 as Λ) or -c(oHCh2)p2_, and if the nr4r5 heterocyclic ring is substituted by Rl8, then Rl8 is not bound to the nr4r5 ring-nitrogen ring. The upper is substituted. When R4 and R5 are taken as _(αί2)Λ or part>(CH2)p2_ or even)ρ3_χ5·(CH2)/- or -C(0>x5_(CH2)p5_ or any Part of the unsaturated derivative, wherein the NR4R5 heterocyclic ring is fused to the phenyl ring, optionally substituted on the phenyl group with one or two of the following groups: a tooth atom, a C12 alkyl group, a fluoroalkyl group. , q-2 alkoxy or heart fluoroalkoxy; in a particular embodiment of the invention, NR4R5 is

Or substituted: a halogen atom, / a phenyl group is optionally one or two of the following groups: Cl.2 alkyl, Cl fluoroalkyl, Q-2 alkoxy or. Fluoroalkyloxy. In a specific implementation of the present invention, 'and/or may be independently Ο or 卜 n/-NR14 or or ～1~, or one (meaning 21 2 together with R1 3 or R7 and R8 together <CH2 _N(Rl 4 ^CH2 D or (that is, R12 and R13 or r7 and R8 together are _(CH2)2 _〇_(cH2)2 _)

: "N ρ or NMe2 R15 is preferably a hydrogen atom (Η) or a q _4 alkyl group (e.g., tBu or Ci 2, for example, methyl); and R15 is more preferably a hydrogen atom (H). However, R4 and R5 are preferably not used together, meaning that the NR4R5 ring system described herein is not used together in the form of 87841-960303-中.doc -49-1283678. (Like the preference is as for R5, for R5a, but 115& cannot be a hydrogen atom. R5a is preferably ethyl). In a particularly preferred embodiment, NR4R5 is NR4R5 as defined in any of the following examples: Examples 21-98, 100-182, 187-188, 191-200, 201-203, 210-353, 355-651, 653- 658 and 660-664. The compound of the formula (1) or a salt thereof is: 4-(cyclopentylamino)-1·ethyl-lH-p is more than [3,4-b]p than 嗓_5·reactive acid, 4 -(cyclohexylamino)-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester, 1-ethyl-4-(tetrahydro-2H- shouting- 4-aminoamino)-1Η-ρ is more than [3,4-b]external b--5-deoxyethyl ester, 4-[(1-methylhexahydropyridin-4-yl)amino] Ethyl 1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate, 4-[(1·ethinylhexahydropyridin-4-yl)amino]ethyl _1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester, 4-(cyclopentylamino)-1-methyl-1H-P than 嗤[3,4-b> ratio -5-5-Repulsive B, 1-methyl-4-(tetrahydro-2H·piperidinyl)-1Η-pyrazolo[3,4_b]pyridine-5-carboxylic acid ethyl ester, 1 -ethyl-4_[(3S)-tetrahydrofuran-1-ylamino]-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester, 1-ethyl-4_[(3R)-tetra Ethylfuranylamino]411_pyrazolo[3,4-hexa]pyridinecarboxylic acid ethyl ester, 1-ethyl-4-(tetrahydro-2H-thiopiperan 4-ylamino)-1Η_ Ethyl pyrazolo[3,4-b]pyridine-5-carboxylate, 87841-96〇3〇3_中.doc -50- 1283678 1-ethyl-4-(tetrahydropyrimidin-3-ylamine -1Η-pyrazole [3,4_b]ethyl pyridine-5-carboxylate, ethyl 4-(cyclopropylamino)ethylethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate, 4- [(1 ,1-dihydrotetramethylene sulfonate-3-yl)amino]-1·ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate, 4_[(1,1 _Dihydrotetrahydro-2H-thiopiperan-4-yl)amino]-1-ethyl_1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester, N-benzyl Small ethyl (tetrahydro-2-indolyl-pyran-4-ylamino)·1Η-pyrazolo[3,4-b]pyridine·5-carboxamide, 1-ethyl-N_(4-fluoro Phenyl)-4-(tetrahydro-2H-piperidinylamino)-1Η-pyrazolo[3,4-b] oxime-5-carbamide, N-cyclopentyl-4- (cyclopentylamino)_1_ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, 4-(cyclohexylamino)cyclopentyl-1-ethyl-1H -pyrazolo[3,4-7>pyridin-5-carbamide, N-cyclopentyl small ethyl ice (tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazole [3,4-b]pyridine-5-formamide, 4-[(1-ethylhydrazinohexahydropyridin-4-yl)amino]-N·cyclopentyl-1-ethyl-1H-pyridyl Zoxa[3,4-b]pyridine-5-carboxamide, N_cyclopentyl-1_ethyl_5-(tetrahydropyrrole·μ-ylcarbonyl)_1H_pyrazolo[3,4-7] Pyridinium, N-cyclohexane -1ethyl-5-(tetrahydropyrrole+ylcarbonyl)-1Η·pyrazolo[3,4-7]pyridinium, 1-ethyl-5-(tetrahydrofuran-fluorenylcarbonyl) Hydrogen_211_piperidinyl-m-pyrazolo[3,4-b]pyridin-4-amine, 4-(3⁄4:pentylamino)_1_ethyl-N-pyridin-4-yl Methyl)_1H_pyrazolo[3,state pyridine 5-pyridylamine, 87841-96〇3〇3·中.doc -51 - 1283678 4-(cyclohexylamino)ethylidene-Ν- O-pyridin-4-ylmethyl)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-N-(pyridin-4-ylmethyl)-4- (tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 4-(cyclopentylamino)-1-ethyl -1H-pyrazolo P,4-b]pyridine-5-carboxamide, 4-(cyclohexylamino)-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5· Formamidine, 1·ethyl_4_(tetrahydro-2H-piperidin-4-ylamino)_1H-pyrazolo[3,4-b]pyridine_5-formamide, N_mercapto 4-(cyclopentylamino)ethylidene-1H-pyrazolo[3,4-b]pyridine-5-carbamimidyl, fluorenyl-4-(cyclohexylamino)ethylidene-1H- Pyrazolo[3,4_b]pyridine-5-carboxamide, 4-[(1-ethylhydrazine hexahydro? Specific attack-4_yl)amino]-1^-y-yl-1-ethyl-111-leaf 1: spit[3,4-b]p than attack-5-cartoamine, 4-(ring Amylamino)ethyl-N-(2-ethylbutyl)·1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 4-(cyclohexylamine) small B --N-(2-ethylbutyl)-1 Η-pyrazolo[3,4_b]pyridine-5-decylamine, 1-ethyl-N-(2-ethylbutyl)-4_(four Nitrogen-2H-pyran-4-ylamino)-1Η-ρ than ton[3,4-b]pyridine-5-carboxamide, 1-ethyl-N-(2-ethylbutyl) 4-[(1-methylhexahydropyridin-4-yl)amino]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, 4-[(1-ethenyl) Hexahydropyridyl)amino]_1·ethyl-N-(2-ethylbutyl)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 4-(cyclopentyl) Amino) small ethyl-N-(4-fluorophenyl)-1H-p than salino[3,4-b]exyl b--5-carbamamine, 87841-960303-中.doc-52· 1283678 4-(Cyclohexylamino)ethylidene-N-(4-fluorophenyl)-1Η-exo b唆[3,4-b]indole-5-formamide, 1-ethyl- N-(4-fluorophenyl)-4-[(1-mercaptohexahydropyridyl)-yl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, 4- [(1-acetic acid-based chloro-p-buty-4-yl)amino]-1-ethyl- N-(4-Phenylphenyl)-1H-p ratio also [3,4-b]pyridine-5-carboxamide, 4-(cyclopentylamino)-1-ethyl-N-positive- propyl-1H-P is more than 唆[3,4-b]externate b-5-cartoamine, 瘫4-(cyclohexylamino)-1-ethyl-N-n-propyl_1H- Pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-N-n-propyl-4-(tetrahydro-2-indole-piperidin-4-ylamino)_1Η-pyridyl Zoxao[3,4-b]pyridine-5-carboxamide, 4-[(1-ethyl acanthoprum p-precipitate-4-yl)amino]-1-ethyl-N-n-propyl Base-lH-p is more than 唆[3,4-b], b is _5_cartotenamine, N-benzyl small ethyl-4-[(l-methylhexahydropyridin-4-yl)amine -1H-pyrazolo[3,4-b] oxime--5-cartoamine, 4-[(1-ethenylhexahydropyridin-4-yl)amino]-1-ethyl -N-(pyridin-4-ylmethyl)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, N-benzyl-4-(cyclopentylamino)-1_ Methyl-1H-pyrazolo[3,4-b]pyridine_5.carbamamine, N-mercapto-4_(cyclohexylamino)-1_methyl-1H-pyrazolo[3,4 -b]pyridine-5-carboxamide, N-benzyl-1·methyl pipe (tetrahydro-2H-piperazin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine - 5-Protonamine, 4-(cyclopentylamino)-N-(2-ethylbutyl)-1-methyl-1H-pyrazolo[3,4 Pyridine-5-carbamide, 4-(cyclohexylamino)-N-(2-ethylbutyl)-1.methyl-1H-pyrazolo[3,4-b]pyridine_5_ A 87841-9603〇3·中.doc -53- 1283678 decylamine, N-(2-ethylbutyl)-1_methyl_4_(tetrahydro-2H-piperazin-4-ylamino)· 1Η-pyrazolo[3,4-b]p ratio bit-5-carbamamine, 4-(cyclopentylamino)-N-(4-fluorophenyl)sodiummethyl-1H-pyrazole [3,4-b]pyridine-5-formamide, 4·(cyclohexylamino)·Ν_(4·fluorophenyl)-1-methyl-1H-pyrazolo[3,4-b] Pyridine-5-formamide, N-(4-fluorophenyl)-1-methyl·4-(tetrahydro-2H-piperazin-4-ylamino)-1Η-pyrazolo[3,4 VII] external yttrium-5-formic acid amine, 4-(cyclopentylamino)·1-methyl-1H-P than olfactory [3,4-b> butyl _5-formic acid amine, 4_(ring Hexylamino)methanol-1H-P is more than [3,4-b]p than pent-5-carbamide, 1-methyl-4-(tetramethylene-2H-piperidinylamino) -1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 4-[(1-ethylhydrazinium hexahydropyridin-4-yl)amino]-N-benzyl-1_ Methyl-1H-pyrazolo[3,4-b>pyramid-5-carbamide, 4-[(1-ethylhydrazinohexahydropyridin-4-yl)amino]-N-(2- Ethyl butyl)-1-methyl-1H-exopurin and [3,4-b]p ratio -5-Artemisamine' 4-[(1·Ethyl hexahydropyridin-4-yl)amino]-N-(4-fluorophenyl)_1_methyl_1H-pyrazolo[3, 4-b]p butyl-5-cartoamine ' 1 -ethyl-N-methyl-4_(tetrahydro-2H·pipelanylamino)-iH-pyrazole[3,4-7] Bis-5-carbamamine, 1-ethyl-N,N-dimethyl-4-(tetrahydro-2H-piperidin-4-ylamino)·1Η-pyrazolo[3,4 -b] pyridin-5-formamide, 1-ethyl-N-ethyl-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4_b] Pyridine - 87841-960303-中.doc -54- 1283678 5-Protonamine, 1-ethyl-N-isopropyl-4-(tetrahydro-2H-pyran-4-ylamino)-1Η- Pyrazolo[3,4-b]pyrrolidine-5-SiSiamine, N.benzyl-1-ethyl-4-[(3S)-tetrahydrofuran-3-ylamino]-1H-pyrazole [3,4-b]pyridine· 5-cartoamine, N-mercapto-1-ethyl-4-[(3R)-w-nitropyran-3-ylamino]-lH_T^b 3,4-b]p-precipitate- 5-cartoamine, N-mercapto-1-ethyl-4_(tetrahydro-p-phenant-3-ylamino)_1Η·ρ ratio spit [3,4 -b]p-precipitate-5-formamide, N-yl--4-(cyclopropylamino)ethylidene-IHh? than succinyl[3,4-b]p than 5·carbamamine , N-Henki·4-[(1,1-dioxytetrahydrocyclopropenyl-3-yl)amino]] Base-iH-p ratio spitting [3,4-b]pyridine-5-methanamine, N-benzyl-4-[(1,1-dioxytetrahydro-2H-thiopyranyl-4) Amino group]-1_ethyl_ih_ 匕 匕 并 [3,4-b> 淀 -5-5-formamide, N-benzyl-1-ethyl ice (tetrahydro-; 2H-sulfur Desmodium-4-ylamino)-1Η-pyrazolo[3,4-b] oxime-5-carbamide, 1_ethyl-Ν·(4·fluorophenyl)-4- [(3S)-w-hydrofuranylamino]]Η·pyrazolo[3,4-b]pyrazine-5-carboxamide, 1·ethyl·Ν-(4-fluorophenyl) ice [ (3R)_tetrahydrofuranylamino]pyrazolop,4-b] oxime-5-cartoamine^1-ethyl-N-(4-fluorophenyl)-4_(tetrahydro- 2H-thiopiperan-4 amino group >m_pyrazolo[3,4-b]p than lake-5-cartoamine, 1-ethyl-N-(4-fluorophenyl) -4-(tetrahydrothiophene-3-ylamino)_1H_pyrazolo[3,4-7]pyridine-5-cartoamine, 87841-96〇3〇3-中.doc -55- 1283678 4 -(cyclopropylamino)-1_ethyl_Ν·(4)fluorophenyl)_1H_pyrazolo[3,4_b]pyridine-5-carbamimidamine, 4-[(1山二氧化tetrahydrothiophene _ 3_yl)amino]-1-ethyl-N-(4-fluorophenyl)-1Η-pyrazolo[3,4-b]p than lake-5-cartoamine, or 4-[( 1,1_dihydrotetrahydro-2H-thiopiperine Amino] ethyl _N_ (4_ fluorophenyl HH- pyrazolo [3,4 seven] pyridine _5_ A Amides; the "salt thereof, for example the pharmaceutically acceptable salts thereof. The structures of these specific compounds are shown in Examples 1 - 98 below. Alternatively, the compound of the formula (I) or a salt thereof is particularly preferably: 1-ethyl-N-[4_(methylsulfonyl) aryl] ice (tetrahydro-2H-piperidin-4-ylamino)_1H- Pyrazolo[3,4-b]pyridine-5-carboxamide, (1-{[1-ethyl_4_(tetrahydro-2H-piperidinyl)-1Η-pyrazolo[3 ,4_b]pyridin-5-yl]carbonyl}hexahydropyridin-3-yl)methylcarbamic acid, third butyl ester, 1-ethyl_N_[3-(methylsulfonyl) aryl]_4- (tetrahydro-2H-piperazin-4-ylamino)-1Η-pyrazolo P,4_b]pyridine-5-formamide, 1-ethyl-5-{[5-methoxy_6· (trifluoromethyl)·2,3_dihydro-1H-indole-1_yl]carboxy}-indole-tetrahydro-2-indole-pyran-4-yl-1Η-pyrazolo[3,4_b] Pyridine-4_amine, N-[(5-chloropyridin-2-yl)methyl]_1_ethyl-4_(tetrahydro-2H-pyran-4-ylamino)-1Η-pyridyl [3,4-b]pyrazine-5-formamide, N-(4-gasbenzyl)_1_ethyl-N-isopropyl-4-(tetrahydro-2H- brit-4) Amine Group>1H-pyrazolo[3,4-b]pyridine-5-carboxamide, N-(3-chlorobenzyl)_1·ethyl_Ν·(2·hydroxyethyl)-4- (tetrahydro-2H-pyran-4-ylamino)·1Η-ρ ratio also [3,4-b]external t-bend-5-formamide, 1-ethyl-Ν-[(5· Methyl-3-phenyliso-17 Jun-4-yl)methyl]-4 -(tetranitro-2H_ shouting-4_ 87841-960303-medium.doc -56- 1283678 arylamino)-1Η-ρ ratio also [3,4-b> than 嗓-5-carboxylic acid amine, N- (2-di-di-butyl-butylethyl)-1_ethyl_4-(tetrachloro-2H-Butan-4-ylamino)-1Η-ρ-pyrazolo[3,4-b]pyridine -5-Protonamine, 1-ethyl-4_(tetrahydro-2H-piperidin-4-ylamino)-indole-(1,3-oxazol-2-ylmethyl)-1Η-pyrazole And [3,4-b]pyridine-5-formamide, 1-ethyl-N-(pyrimidin-4-ylmethyl)_4·(tetrahydro-2H-piperidin-4-ylamino)- 1Η_pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-N-[(2-methyl·1,3-pyrazol-4-yl)methyl]-4 -(tetrahydro-2H-piperidinylamino)_1H-pyrido[3,4-b]pyridine-5-carboxamide, Ν·[3-(T-butoxymethyl)hen Base]-1-ethyl winter (tetrahydro-2H-piperidin-4-ylamino)_1Η-ρ ratio spit [3,4-b] outer t; lake-5-formic acid amine, 1-ethyl -N-{2-[methyl(methylsulfonyl)amino]ethyl}-4-(tetrahydro-2H-piperazin-4-ylamino group than sir[3,4-b]p ratio Ding-5-cartoamine, 1-ethyl-N-(pyroxy-2-ylmethyl)-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[ 3,4-b]pyridine-5-formamide, 1-ethyl-5-{[4-(pyridin-2-ylcarbonyl) Hexahydropyranin-1-yl]carbonyl}_N-tetrahydro-2H-piperidin-4-yl-1H-pyrazolo[3,4-b]pyridine-4-amine, Ν·(2-chloro 5--6-fluorobenzyl)ethylidene 4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide , 1-ethyl-Ν·[(6-费基-1,6-^-rho-p-but-3-yl)methyl]-4-(tetrachloro-2Η-喊喃_4_ylamino -1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, N-[3-(aminocarbonyl)indenyl]sodiumethyl-4-(tetrahydro-2H-pyran- 4-aminoamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-N-{4-[(methylamino)carbonyl]phenyl}-4 -(tetrahydro-2H-piperazin-4-ylamino)-1Η- 87841-96〇303-中.doc -57- 1283678 外匕吐和[3,4-b]叶叶边-5-甲Indoleamine, 1·ethyl-N-[2-(l-methyl-1H-mist-4-yl)ethyl]-4-(tetrahydro-2H-bran-4-ylamino)- 1Η-ρ比峻和[3,4-b]p ratio _5_甲甲胺,Ν-{2·[(anilinocarbonyl)amino]ethyl}sodiumethyl-4-(tetrahydro- 2H_旅喃_4_ylamino)-1Η_pyrazolo[3,4-b]pyridine-5-carboxamide, 1·ethyl-N-(1H-tetra-5-ylmethyl )-4-(tetrachloro-2H-^py-4-ylamino)-1Η-ϊτ is more than [3,4_b]pyridine_5_A Indoleamine, 1-ethyl-4-(tetrazol-2H-pyran-4-ylamino)-indole-[2-(1Η-1,2,4_trisinyl)ethyl]-1H ·pyrazolo[3,4-b]pyridine-5-carboxamide, 2- [{[1-ethyl_4-(tetrahydro-2H_ shomo-4-ylamino)-1Η-ρ Ratio is also [3,4-1 small ratio of 5-amino]carbonyl}(methyl)amino]ethylaminocarbamic acid tert-butyl ester, 1-ethyl-4-(tetrahydro-2Η· Piperaz-4-ylamino)-N-[4-(trifluoromethyl)phenyl]_1H-pyrazolo[3,4-b]pyridine-5-carboxamide, 4-({[1 -ethyl·4-(tetrahydro-2H·piperidin-4-ylamino)-1Η-pyrazolo[3,4_b]pyridin-5-yl]carbonyl}amino)hexahydropyridine small carboxylic acid Tri-butyl ester, 1-ethyl-N-{3-[(polymethyl)amino]propyl}-4-(tetrahydro-2H-mum-4-ylamino)-1H-pyridyl Zoxa[3,4-b]pyridine-5-carboxamide, N-[2-(dimethylamino)indolyl]-1-ethyl winter (tetrahydro-2H-piperidinylamino) -iH-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-indole-[(1·ethyltetrahydropyrrol-2-yl)methyl]_4-(tetrahydrogen) -2H-pyran-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-N-(tetrahydrofuran-2-ylmethyl) ice (tetrahydro-2H-piperidin-4-ylamino)-iH-pyrazolo[3 ,4-b]pyridine-5-methanamine, 1_ethyl-N-tetrahydro-2H-methylene-4-yl-4-(tetrahydro-2H-hamo-4-ylamino)_ih- Pyridin 87841-960303-中.doc - 58 - 1283678 and [3,4-b]pyridine-5-formamide, N-{4-[(dimethylamino)sulfonyl]benzyl} small B Base (tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrido[3,4-b]pyridine-5-carboxamide, 1-ethyl-N-{3-[( Methanesulfonyl)amino]yl}-4-(tetrahydro-2-indole·piperidinylamino)_1Η-ρ is more than [3,4-b]p than 5-Metamine , M[l-ethyl_4.(tetrahydro-2Η-piperidin-4-ylamino)_1Η-pyrazolo P,4-b]pyridin-5-yl]carbonyl}hexahydropyridin-2- Indoleamine, 1·ethyl-indole (4-methoxyphenyl)-4_(tetrahydro-2H-piperazin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine -5-Protonamine, 1-ethyl·N-[3_(2-ketotetrahydrop-pyryl-1)propyl]-4-(tetrahydro-2Η-»派喃·4-yl Amino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-N-[2-(l-methyltetrahydropyrrole-2-yl)ethyl] _4-(tetrahydro-2H-piperidin-4-ylamino)_1Η-ρ ratio and [3,4_b] outside 1: Violation-5-methylamide, 1-ethyl-N-pyridin-3 -ylmethyl)-4_(tetrahydro-2H-pyro- 4-ylamino -1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-N-(l-methylhexahydropyridin-4-yl)-4-(tetrahydro-2H- Miso-4-ylamino)_1Η·pyrido[3,4-b]pyridine-5-carboxamide, 1-ethyl-N-(l-ethylpropyl)-4-(tetrahydrogen) -2H- 喃 -4--4-ylamino)-1Η-pyrrolidino P,4_b]pyridine-5-carboxamide, 1-ethyl-N-(2-hexahydropyridine small ethyl)_4·( Tetrahydro 2H-piperazin-4-ylamino)-1Η-ρ is more than [3,4-b]pyridine-5-carboxamide, 1-ethyl-N-(3-moffone- 4-ylpropyl)-4-(tetrahydro-2H-pyran-4)ylamino)-1Η-exopurin and [3,4-b]pyridine-5-carboxamide, N-(3 -ethoxypropyl)sodiumethyl-4-(tetrahydro-2H_ shouting _4_ylamine-based ton and 87841-96〇303-中.doc-59- 1283678 [3,4-b> Bishen-5-carbamamine, N_(cyclohexylmethyl)-1_ethyl ice (tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b] P-Phenan-5-cartoamine, N-[3-(dimethylamino)propyl]sodiumethyl pentyl (tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[ 3,4-7]pyridine-5-carbamamine, 1-ethyl-N-neopentyl-4-(tetrahydro-2H-pyran-4-ylamino)-1Η-pyrazolo[3, 4-b]Pyramid-5-cartoamine 1_Ethyl-N_(4 _Methoxybenzyl)-4_(tetrahydro-2H-pyran-4-ylamino)-1Η·峨唆[3,4_b]External 1: Ammonium-5-formic acid amine, 1-ethyl- N_{2-[(phenylsulfonyl)amino]ethyl}ice (tetrahydro-2H-piperidin-4-ylamino)-1Η_ρ ratio also [3,4-b] outer 1: lake- 5. Myramine, N-indole (ethylamino)ethyl]_1_ethyl_4_(tetrahydro-2Η-piperidin-4-ylamino)·1Η-pyrazolo[3,4- b]pyridine-5-carboxamide, 1-ethyl_N-{2_[(methylsulfonyl)amino]ethyl}-4-(tetrahydro-2H-piperazin-4-ylamino) -1H-carbazolo[3,4-b]pyridine-5-carbamamine, 1·ethyl-N-methyl-N heptaidine-4-ylmethyl)-4-(tetrahydro-2H -piperazin-4-ylamino)·1Η_pyrido[3,4-b]pyridine-5-carboxamide, 1-ethyl-Ν·{2-[(2-methoxyphenyl)( Methyl)amino]ethyl}-4-(tetrahydro-2H.piperidin-4-ylamino)-1Η-ρ than oleno[3,4-b]pyridine·5·carbamidine, 1 -ethyl-indole-(2-indolyl-2-phenylethyl)-4-(tetrahydro-2Η-^an-4-ylamino)_1Η-ρ-pyrazolo[3,4-b] Pyridoxine: 5-carbamamine, N-(2,5-difluoroaryl)-1-ethyl-4-(tetrahydro-2H-bungan-4-ylamino)-1H-p ratio Tons of |; 3,4-b]pyridine-5-formamide, 1·ethyl ice (tetrahydro-2H _piperazin-4-ylamino)-N-[4-(trifluoromethyl)-yl]-1H-pyry 87841-960303·中.doc -60- 1283678 oxazo[3,4-b]pyridine -5-Mergamine, N,l-diethyl-N-propyl-4_(tetrahydro-2H-bran-4-ylamino)-1Η-pyrazolo[3,4-b] p Bishen-5-formamide, N_cyclopropyl-1_ethyl-4_(tetrahydro-2H_ shout-4-ylamino)·1Η_ρ ratio and [3,4-b] Ammonium-5-formic acid amine, N_(2-amino-2-ketoethyl)> 1-ethyl_4_(tetrahydro-2H-bran-4-ylamino)-lH-exo bazole [3,4-b]pyridine-5-carboxamide, 1"·ethyl_N-(3_methyllactosyl)-4-(tetrazo 2 Η 喊 -4- -4-ylamino)- 1Η_ρ ratio is also P,4-b]pyridine_5·carbamamine, Ν"·(3,4_<one gas sulfhydryl)-1-ethyl-4-(tetrazine 2 Η^^ -4-ylamine Base)_1Η-ρ than ton[3,4-b]pyridine-5-formamide, 3-({[1-ethyl-4·(tetrahydro-2-indolyl-4-ylamino)) -1Η-pyrazolo[3,4-b]pyridin-5-yl]carbonyl}amino)propionic acid ethyl ester, N-(l-benzylhexahydroexoacridin-4-yl)·1·B 4-(tetrahydro-2H-sulphant-4-ylamino)-1Η-pyrido[3,4-b]pyridine-5-carboxamide, N-butyl-4·{[1 -ethyl-4-(tetrachloro-2H-^py-4-ylamino) And [3,4-b]exoazin-5-yl]carbonyl}hexahydropyrazine-1-carboxamide, 1_ethyl-4_(tetrachloro-2H-pyran-4-ylamino) -Ν-(1,3,4-ρ2,2,2-yl)-1H-p, benzo[3,4-b]pyridine-5-carboxamide, Ν-(2,3·dichloride -1H-Is-2-yl)-1-ethyl-4-(tetrazine-2H-bromo-4-ylaminobispyrazolo[3,4-b]pyridine-5-carboxamide, 1 -ethyl-N-[2-(2-mercapto-paste), ethyl]-4-(tetrahydro-2H-bromo-4-ylamino)_1H-pyrazolo[3 , 4-b]pyridine-5-carbamide, N-(3,4-dimethoxyaryl)ethylethyl-4-(tetrahydro-2H-»7 guran-4-ylamine ratio 87841-960303-中.doc -61 · 1283678 oxazo[3,4-b]pyridine-5-carboxamide, N-(3-chlorobenzyl)-1_ethyl-4-(tetrahydro-2H _piperidin-4_ylamino)_ih-pyrazolo[3,4_b] 12 than lake-5-cartoamine, 1-ethyl-5·[(4_methylhexahydropyrazine_1_ Carbonyl]-N tetrahydrogen such as _pyranyl-winter _lH_pyrazolo[3,4-b]pyridinium, 1-ethyl benzo(2-hydroxyethyl) ice (tetrahydro-2H- Piperidinylamino)-lH-pyrazolo[3,4-7]pyramid-5-cartoamine, 1-ethyl-5·{[4·(4-methoxyphenyl)hexahydro Pyridin-1-yl]carbonylbu N_tetrahydro·2H_pyran-4-yl-lHwb ton[3, 4-b>Biprecipitate_4_amine, 1-ethyl-N-{4-[(methylsulfonyl)methyl]phenyl b 4-(tetrahydro-2-indole) Base) _ 1H-pyrazolo[3,4-b]pyridine-5-formamide, N-[3-(dimethylamino)_3-ketopropyl]_1_ethyl ice (tetrahydro- 211_pyran-4-ylamino)-lHw is more than [3,4_b] external b-precipitate-5-formamide, 1-ethyl-N-[(l-methyl_1Η·imidazole-5 -yl)methyl]_4-(tetrahydro-2H· shout-4-ylamino)-1Η·ρ ratio and [3,4-b>pyramid-5-formamide, 1·ethyl _Ν_{4·[(Methylamino) hydrazino]phenyl} ice (tetrahydro-2H-furan-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine·5· Formamide, Ν_(2-cyanoethyl)-1_ethyl_4-(tetrahydro-2Η- sher-4-ylamino)·1Η-ρ 比吨[3,4-b> Bishen-5·carbamamine, 1-ethylmethyl-indole-[(5·methyl-di-n-butyl-2-yl)methyl]-4-(tetrahydro-2H-mouth -4- Amino group)_1Η·ρ ratio spit[3,4-b]external b-precipitate-5-cartoamine, 1-ethyl-N-[(l-methyl·1Η·pyrazole-4_yl) Methyl] ice (tetrahydro-2H-piperazin-4-ylamino)_1H-external b-[3,4-b> than attack·5-formamide, 1-ethyl-fluorene-methyl -N-[(l-methyl_1Η-味峻_2_yl)methyl]-4-(tetrahydro-2 -旅喃-4_ 87841-96〇3〇3·中.doc -62- 1283678 胺amino)_1H-p is more than [3,4-b]p than _5_carbamamine, 1-B Base-4-(tetraqi-2H-pyran-4-ylamino)-N-(2-p-cephen-2-ylethyl than spit [3,4_b> butyl-5-carbamide , N-[2-(4-ratyl)ethyl]-1-ethyl-4-(tetrahydro-2H-^-endo- 4-ylamino)-lH> than tons [3,4 -b]pyrazine-5-formamide, 1·ethyl-N-[2-(2-methoxyphenyl)ethyl]-4·(tetrahydro-2H-furan-4-ylamino) ·1Η>Bizozolo[3,4-b]pyridine-5-carboxamide, 4-(cyclohexylamino) small (3-ethoxy-3-butanylpropyl than spit [3,4 -b]p-precipitate-5·heric acid ethyl ester, 1-n-propyl-4-(tetrahydro-2H-fluoren-4-ylamino)-1Η·ρ than 唆[3,4- b]p-precipitate-5-oleic acid ethyl ester, 1-(2-hydroxyethyl)-4-(tetrahydro-2H-piperidinylamino)-1Η-pyrazolo[3,4-b] Pyridine-5-carboxylic acid ethyl ester, N-[4-(methylsulfonyl)benzyl]sodium n-propyl-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyridyl Oxazo[3,4-b]pyridine-5-carboxamide, Ν-(4.fluorophenyl)-1 n-propyl-4_(tetrahydro-2-indolyl-4-ylamino)- 1Η·pyrazolo[3,4-b]pyridine-5-formamide, 1-ethyl-6-methyl· 4_(tetrahydro-2H_piperidinylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxylate ethyl ester, 4-(cyclohexylamino)_1_ethyl-6 -ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester, 4-(cyclohexylamino)ethylethyl-6-methyl_N-[4-(methylsulfonate) Indenyl) fluorenyl]-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, N-benzyl-4-(cyclohexylamino)ethyl-6-methyl-1H -pyrazolo[3,4_b]pyridine-5-carboxamide, 87841-960303-中.doc -63- 1283678 4- (cyclohexylamino)-1•ethyl-N-(4-phenylphenyl) -6-Methyl to benzo[3,4_b]P than y- 5-carbamamine, 4-(cyclohexylamino)-1-ethyl-6-fluorenyl-N_[4_(trifluoromethyl) Base) syl-pyrazolo[3,4-b>pyramid-5-carbamide, 4-(cyclohexylamino)-N-(2,3-dihydro-1H-hetero-2-yl) _1_ethyl_6_methyl-1H-P is more than spit [3,4-7> bis--5-carbamamine, N-mercapto-1-ethyl-6-methyl-4-( Tetrahydro 2H-h-ylamino)1Η·ρ ratio and [3,4-b]p than pent-5-carbamide, N-fluorenyl small ethyl-4-[(2·keto) Nitros-7-ylamino)amino]-1H-pyrazolo[3,4-b>pyramid-5-carbamide, N-benzyl-1-ethyl_4_[(3_ Light-based cyclohexyl)amino]_1H_pyrazolo[3,4-b]pyridine- 5_ decylamine, N-benzyl-1-ethyl_4-[(4-cyclocyclohexyl)amino]]ih-pyrazolo[3,4-b]pyridine_5_ 曱siamine, N- Benzyl small ethyl-4_[(3-carbylcyclopentyl)amino]-1H-pyrazolo[3,4_b]pyridine-5-carboxamide, N_benzyl_1_ethyl·4 -[(4-Ketylcyclohexyl)amino]]H-pyrazolo[3,4-b]pyridine-5-carbamimid; a salt thereof, for example, a pharmaceutically acceptable salt thereof. The structures of these specific compounds are shown in Examples 100-201 below. Alternatively, the compound of the formula (I) or a salt thereof may be: 1-ethyl-N-(2-hydroxy-1-methylethyl>4-(tetrahydro-2H-piperazin-4-ylamino)- 1Η-叶匕峻和[3,4-b]pyridine·5-formamide or (2S)_2-({[1_ethyl_4_(tetrahydro-2Η·piperidin-4-ylamino)-1Η) - oxazolo[3,4_b]pyr 87841-96〇3〇3_中.doc-64 - 1283678 ound-5-yl]amino}amino)-3-methylpropionic acid methyl ester; or a salt thereof, For example, a pharmaceutically acceptable salt thereof (see, for example, (10) or a compound of the formula (I) or a salt thereof is selected from the group consisting of A human n shells 1 to 664, as a θ substance or a salt thereof, for example, which is pharmaceutically acceptable The structure of the two substances is shown in the following examples 204 to 664. The escaping e-learning can be Γ 式 式 _ _ _ _ _ _ _ _ _ _ _ _ _ _

X (ΙΑ) where: X is NR4 R5 or a, wherein R is hydrogen, c!-2 alkyl or Ci 2 fluoroalkyl, and R is hydrogen Cl. 8: ki, Cl·8 fluoroalkyl Or c3.8 cycloalkyl, phenyl 'optionally substituted with one or two of the following groups: a tooth atom, a C 2 alkyl group, a trifluoromethyl group, a Cl 2 decyl group or a trifluoromethoxy group, or R5 has the subtype (8), (y) or (8): _(CH2)n Γ R'D . , eJ - (called L (y) (z) where in the subtypes (x) and (8), n = 1 or 2 And in the subtype (y), (d) or 2; wherein in the subtypes (X) and (y), no or one or two of A, B, D, E & F are nitrogen' and the remaining A, b , d, e and F are (3) or (10), where r6 is 卣原(X)

Sub, Ch alkyl, c 4 fluoroalkyl

Cl-2 alkoxy group, Q-2 fluoroalkyl alkoxy group, 87841_96〇3〇3_中.doc-65- 1283678 烧基根根(Cl_2 alkyl·S(V), Ci 2 alkyl base code _ , the rule -s〇2-, RWca, r7r8n, 0H, Ci 4 alkoxymethyl or Ci 2 alkyl-s〇2_CH2_, wherein R7 and R8 are independently hydrogen or Cu alkyl; In Z), G is hydrazine or 8 or service 9, wherein the alkyl group or Ch fluoroalkyl group; no or one or two of L, is nitrogen; and the remaining J, L, Μ and Q are CH or CR6, wherein R6 Is as defined herein; or R4 and R5 are taken as _(CH2)p-, wherein p = 3, 4 or 5 (preferably p = 4); R a is a Ch alkyl group; Cl-8 fluoroalkyl; C3 8 cycloalkyl; phenyl, optionally substituted by one or two of the following groups: a functional atom 'Ci-2-alkyl, trifluoromethyl, Α-2 alkoxy or trifluoromethoxy; or RSa has Sub-formula (8), (y) or (z) as defined herein; R3 is a C3_8 cycloalkyl or heterocyclic group

Wherein Y is 0, S, SOpiLNR10; wherein R1〇 is hydrogen, Ci-4 alkyl, Ci 2 fluoroalkyl, ¢:(0)4 _2 alkyl or c(o)-cf3; and wherein in R3 (: 3·8 cycloalkyl or heterocyclic group is optionally substituted by one or two substituents of OH, q·2 alkoxy, trimethoxy or alkyl; and any of 0H, alkoxy The benzyl or trimethoxy substituent is not substituted at the ring carbon attached to the -NH- group of formula (IA), and is not bonded to any of the ring carbons of the Y group bonded to the heterocyclic group. Substituting; &ri = Ci_4 alkyl 4Ci-2 fluoroalkyl. In the formula (IA), in the subformula (X) and/or (7), preferably no or one or two A, B, D, E and F are nitrogen; none, one, two or three of A, B, D, E and F are CR6; and the remaining A, B, D, E and F are CH. Better 87841·96〇3 〇3·中.doc -66- 1283678 is no or one or two of A, B, D, E and F are nitrogen; no or one or two of A, B, D, E and F are CR6; , B, D, E and F are CH. In the formula (IA), in the subtypes (X) and/or (y), it is preferred that none or one of the eight, eight, 〇, £ and ? In formula (IA), Preferably ⑻ formula: Qian group; phenethyl (Ph_c2H4_); Ye based or phenethyl substituted on the phenyl ring or one of the following groups a single substituent R6 ·

-CH

-CH

Wherein R6a is R6 or (preferably) hydrogen as defined herein. In formula (IA), subformula (y) is preferably: R6 or preferably as defined herein

Wherein R6a is hydrogen free.

Examples 1-99 are examples of compounds or salts of the second aspect of the invention (formula (IA)). According to a third aspect of the present invention, there is provided a compound of the formula (IB) or a salt thereof (particularly a salt thereof): ^ HN^ 0

(IB) 87841-960303-φ.άοο -67- 1283678 where: RICh alkyl, (: 3 fluoroalkyl, -CH2CH2OH or -CI^CH^CC^Cu alkyl; R2 is a hydrogen atom (H), Mercapto or Ci fluoroalkyl; R is a substituted C in the case of N; 3 · 8 calcoxy, or optionally substituted heterocyclic group of subtype (aa), (bb) or (cc) ;

(aa) _ (CC) wherein η1 and η2 are independently 1 or 2; and wherein γ is 〇, s, 802 or > Case 10; wherein R10 is a hydrogen atom (Η), C! _4 alkyl (such as A Or ethyl), q fluoroalkyl, CH2C(0)NH2, c(o)nh2, ¢: (0)4-2 alkyl or (:(0) fluorinylalkyl; and wherein in R3, a C3-8 cycloalkyl or a heterocyclic ring of the formula (aa), (bb) or (CC), optionally taken by one or two keto groups (=〇), 〇H, q-2 alkoxy Substituted with a substituent of Ci 2 fluoroalkoxy (eg, trifluoromethoxy) or q _2 alkyl; and wherein any 0H, alkoxy or fluoroalkoxy substituent is not attached (bonded To the R3 ring carbon of the formula (IB)-NH- group substituted by the R3 ring carbon and not bonded to the Y group of the heterocyclic group (aa), (bb) or (CC) Substituted; and X is NR4R5 or 0R5a, wherein: R4 is a hydrogen atom (H); Ci-6 alkyl; (V3 fluoroalkyl; or C2-6 alkyl, substituted by a substituent R11; and R5 is a hydrogen atom (H); a Cu alkyl group; a Cu fluoroalkyl group; a C3_8 cycloalkyl group substituted by a Ci-2 former base 87841-960303-中.doc-68-1283678; or _(CH2)n4-c3_ 8-cycloalkyl, optionally in the -(CH2)n4- moiety or in the C3 8 cycloalkyl moiety, substituted by (^.2 alkyl, wherein η4 is 1, 2 or 3; or R5 is a C2_6 alkyl group substituted by one or two independent substituents R" wherein each substituent R11, irrespective of any other Ri 1 substituent present, is a group of (0H); Oxyl; phenyloxy; anthraceneoxy; -NR12R13; ^15-0(0)^6; -NR15-C(0>0-R16; -NR15-C(0)-NH-R1 5 ; -NR1 ISC^R1 6 ; and any of the Ri 1 substituents, which are 〇H, alkoxy or -NR12R13, are not substituted at any of the oxime or substituted 5-alkyl groups (which are bonded to the nitrogen of NR4R5) Any carbon atom is substituted; or R5 is -(CH2)n 11 <:(0 rape 6 ; ; chr19- C(0)NR12R13 ; -(CH2)n12-C(0)0R16 ; -CHR19-C( 0) 0R16 ; -(CH2)n12· S〇2-NR12R13 ; -(CH2)n12-S02R16 ; or -(CH2)ni2_CN; where nll is 0, 1, 2, 3 or 4, and n12 is 1, 2 , 3 or 4; or R5 is -(CH2)n"_Het, where nl3 is 〇, 1, 2, 3 or 4, and this is a 4_, 5-, 6- or 7-membered saturated or partially saturated heterocyclic ring Containing one or two independent choices from Ο, S and N a ring heteroatom; any ring hetero atom present therein, when ^ is 1 'will not bind to the -(CH2)ni3- moiety, and when nl3 is 〇, it will not bind to the nitrogen of NRW; Any cyclic nitrogen present in and not unsaturated (ie, which does not participate in a double bond) is present as NR17 wherein the RU is as defined herein wherein one or two of the carbon ring atoms are independently substituted with Ci2 alkyl as appropriate; Or R5 is phenyl, optionally substituted by - or two of the following base diagrams: (iv) sub; Ch alkyl (eg Ck alkyl); Cl 2 fluoroalkyl (eg trifluoromethyl) c alkoxy (eg CW finished氧基); Cl. 2 fluoro fluorenyl (9) such as methoxy 1 87841-960303-中 .doc • 69- 1283678 base; <: 2 alkyl sulfonyl (Ci-2 alkyl-S02_) Ci-2 alkyl-so2-nh·; R7R8N-S〇2-; R7R8N-CO-; -NR15-C(0)R16; R7R8N; OH; Ch alkoxymethyl; c 4 alkoxy Base ethyl; c1-2 alkyl _so plant Ch2_; cyano (CN); or phenyl 'as appropriate by one or two fluoro, gas, q _2 alkyl, q fluoroalkyl, Cl - 2 a calcined * or a fluoroalkyl alkoxy group; wherein R 7 and R 8 are independently a hydrogen atom (8); a C 4 alkyl group (for example, a Ci-2 alkyl group, Such as methyl); C: 3·6 cycloalkyl; or phenyl, as the case is replaced by one or two of the following groups: fluoro, gas, Q-2 alkyl, (^ fluoroalkyl, Cle2 Alkoxy or Ci fluoroalkyl alkoxy; or R7 together with R8 is ^- or ^(7)^%)/- or -C(0)-(CH2)n 7 -C(0)- or -( CH2)n 8 -X7 -(ch2 )n 9 - or -c(o)-x7 -(CH2 )n 10 - , wherein: n6 is 3, 4, 5 or 6, and n7 is 2, 3, 4 or 5 (n7 is preferably 2, 3 or 4), n8 and n9 and ni〇 are independently 2 or 3, and χ7 is 〇 or ]^14, wherein R14 is 11 or (:1-2 alkyl; or R5 has Subtype (X), (y) or (8):

Wherein in the subtype (X), n = 1 or 2; in the subtype (y), m = 1 or 2; and in the subtype (z), r = 〇, i or 2; In (X) and (y), no or one or two of A, B, D, E and F are nitrogen; and the remaining A, B, D, E and F are independently CH or CR6; wherein R6 is a self atom ; C 4 alkyl (for example, Ci 2 alkyl); Ci 4 fluoroalkyl (for example, 4 2 fluoroalkyl); C alkoxy (for example, Ci 2 alkoxy); Ci 2 fluoroalkoxy; Ci · 2 Sulfosyl (c 2 alkyl-S〇2_); Ci 2 alkyl _s〇2-NH_; 87841·96〇3〇3_中.doc •70- 1283678 R7R8N-S〇2- ; R7R8N- CO-; -NR15-C(0)R16; R7R8N; oh; gas methyl; (^1-4 alkoxyethyl; (111-2 alkyl-8〇2-(1!112-; cyanide) Base (.1^); or phenyl, optionally substituted by one or two fluoro, chloro, C! _2 alkyl, Ci butyl, C!-2 alkoxy or heart fluoroalkoxy Wherein R7 and R8 are as defined herein; wherein in the subtype (Z), G is hydrazine or S or NR9, wherein R9 is a hydrogen atom (H), a Ci-4 alkyl group or a Ci_4 fluoroalkyl group; None, one, two or three of L, Μ and Q are nitrogen; and the remaining J, L, Μ and Q Independently CH or CR6, where R6 is as defined herein; or R4 and R5 are taken as -(CHdp1- or -C(〇MCH2)p2_ or -(αί2)ρ3_χ5- (CH2)p4_ or -C(0) _X5_(CH2)p5-, wherein: Ρι = 3, 4, 5 or 6 (preferably P = 4 or 5), p2 is 2, 3, 4 or 5 (p2 is preferably 2, 3 or 4), And p3 and p4 and P5 are independently 2 or 3 (preferably independently 2), and X5 is 〇 or NR1 7 ; wherein R17 is a hydrogen atom (H); Q-4 alkyl (for example, (^.2 alkyl) (;: 2 fluoroalkyl; C3_6 cycloalkyl; -(CH2)p6_C(0)R16, wherein p6 is 〇, !, 2 or 3 (p6 is preferably 0); -(ch2)p6-c (o) nr12r13; -(ch2)p6-c(o)〇r16; -S〇2 R ' or + or fluorenyl, wherein phenyl or aryl is optionally one or two at the aromatic carbon atom Substituting the following groups: _Atom, C1-2 alkyl, Ci fluoroalkyl, Ck alkoxy or (fluoroindolyl); and wherein, when R4 is combined with R5, it is -(CH2)pi- Or -C(0)-(CH2)p2-, the NR4 R5 heterocyclic ring is optionally substituted by a Ri 8 substituent, wherein r1 s is: Ch alkyl (eg Cm alkyl); (^-2 halothane) C3-6 cycloalkyl; ci · 2 alkoxy (not bound to NR4R5 ring-nitrogen Ring-carbon substituted); Ci-fluoroalkoxy (not substituted at the ring bonded to Nr4r5 ring-nitrogen); 87841-96〇3〇3-中.doc •71 - 1283678 OH (not Substituted to nr4r5 ring-nitrogen ring-carbon; _(CH2)p7_CXCOR1 6, wherein p7 is 〇, 丄, 2 or 3 (p7 is preferably ^ or ^; ^^^^ C(0 ) 0R16 ; -(CH2)p^〇c(〇)Ri6 ; .(CH2)p7-C(0)NR12R13 ; -(CH2)p7-NR1 5 C(0)R1 6 ; -(CH2 )p 7 - NR15 C(0)NR12 R13 ; -(CH2)P7- NR15C(0)0R16 ; _(CH2 )p 7 _S02 R1 6 ; -(CH2 )p 7 -S02 NR12 R13 ; -(ch2)p7-nr15so2r!6 ; _(CH2)p7_OH; ·(αΐ2)ρ7-〇κ16; or phenyl, optionally substituted by one or two of the following groups: 卣 atom, Ci-2 alkyl, Ci fluoroalkyl, Q-2 Alkoxy or cardinylalkoxy; or R4 and R5 are taken as -(CH2)pi_ or _c(〇)_(CH2)p2- or _(CH2)p3_x5_(CH2 as defined herein) P4- or -C(0)-X5-(CH2)p5-, and wherein the NR4 R5 heterocyclic ring is fused to the phenyl ring, optionally substituted on the phenyl group with one or two of the following groups: _ atom, Alkyl, q-fluoroalkyl, Ck alkoxy or. Fluoroalkyl alkoxy; and r5Hs alkyl; Cu fluoroalkyl; c3_8 cycloalkyl; phenyl, optionally substituted by one or two of the following base diagrams: a tooth atom, a Ci-2 alkyl group, a trifluoromethyl group, Q. 2 alkoxy or trifluoromethoxy; or R5a having the formula (8), (y) or (Z) as defined herein; and wherein: R12 and R13 are independently H; Ch alkyl (eg C a 3 alkyl group; a c3-6 cycloalkyl group; or a phenyl group, optionally substituted by one or two of the following groups: a tooth atom, a Ci-2 alkyl group, a C! fluoroalkyl group, a Q-2 alkoxy group Or a fluoroalkoxy group; or R12 and R13 are _(〇ί2)Λ or -C(〇HCH2)n7- or _C(〇HCH2)n7· is 3, 4, 5 or 6 (n6 Preferably, 4 or 5), η7 is 2, 3, 4 or 5 (n7 is preferably 87841-960303-medium.doc • 72-1283678 2, 3 or 4), and η and η and η1 are each 2 or 3 (preferably independently 2), and X12 is 0 or NR14, wherein R14 is hydrazine or Cb2 alkyl; R15 is a hydrogen atom (H); ¢^4 alkyl (for example or a Ci_2 alkyl group such as methyl a C3-6 cycloalkyl group; or a phenyl group, optionally substituted with one or two of the following groups: a halogen atom, a Cufe group, a q fluoroalkyl group, a C 2 alkoxy group or a heart fluoride alkoxy group; ^alkyl (for example (^ 2 alkyl); (: 3_6 cycloalkyl; pyridyl (eg pyridin-2-yl) or phenyl, optionally substituted with one or two of the following groups: from atom, Q· 2 alkyl, fluoroalkyl, c 2 alkoxy or fluorenyl 1 fluoroalkoxy; and R 19 is a hydrogen atom (H); Q _ 4 alkyl (eg isobutyl, second butyl or oxime) ^基, such as methyl or isopropyl); -(CH2)n2 0 -〇R2 〇, wherein 3 or 4 (preferably i) ' and the ruler ^ is a chlorine atom (11) or a 〇1_4 alkyl group Preferably, it is H); -CH_-OH; -CH2-SH; -CH2-CH2_S_Me; τ group; or (tetra)phenyl)methyl (meaning 4-hydroxy-yl). In formula (ffi) 'In the case where R3 is optionally substituted C38 cycloalkyl, '- or the two optional substituents preferably include (for example, 〇h and/or fluorenyl (IV). In the formula (d), 'in the subtype In the heterocyclic group of (d), (d) or (cc), the substituent or the two substituents preferably include (for example, a fluorene and/or a keto group. The example is the third aspect of the invention (formula_) Example 0 of a compound or salt. Regarding the formula (IAH complex or salt and formula (IBM compound or salt) Preferred or optional characteristics, which are the same or similar to those of the compound or salt of formula (1), all of which are necessary (for example, for the chemical formula, for the R group and/or for S7841 _96〇3〇3·d 〇c -73- 1283678 for substituents) has been implemented. In general, whenever reference is made to Formula (I) herein, then in the alternative embodiments, the reference to Formula 1 applies to Formula (IA) or Formula (IB), where all necessary changes have been Implementation. Salts, solvates, isomers, tautomeric forms, molecular weights, etc. The salts of the compounds of formula 1 are preferably pharmaceutically acceptable due to their potential use in medicine. Suitable pharmaceutically acceptable salts may include acid- or base-addition salts, which are pharmaceutically acceptable acid addition salts, which may be obtained by reacting a compound of formula (I) with a suitable inorganic or organic acid (such as hydrobromic acid, hydrochloric acid, sulfuric acid, Formed by the reaction of nitric acid, phosphoric acid, amber cylinder, cis-dibasic acid, acetic acid, trans-tert-bic acid, citric acid, tartaric acid, benzoic acid, p-toluenesulfonic acid, methanesulfonic acid or sulfonic acid, depending on the situation In a suitable solvent, such as an organic solvent, a salt is obtained which is isolated by, for example, crystallization and filtration. The acid addition salt of the compound of the formula 1 may be, for example, a hydrobromide, a hydrochloride, a sulfate, a nitrate, a phosphate, a succinate, a succinic acid, and a cool An acid salt, a sulfonate, a citrate, a tartrate, a formate, a p-toluenesulfonate, a methanesulfonate or a naphthalenesulfonate. The pharmaceutically acceptable salt addition salt can be obtained by reacting a compound of the formula (1) with a suitable inorganic or organic compound = 20% and optionally adding a base in an appropriate solvent such as an organic solvent. For example, crystallization and filtration are separated. It is a pharmaceutically acceptable B®, a sentence containing and/or, a concentrate and a musically acceptable metal salt, such as a drop-off of an alkali metal or alkaline earth metal hoof, a magnesium salt; Is a pharmaceutically acceptable metal salt of a ":,:, or a group" which may be present in the compound of Formula 1. < </ RTI> Other non-pharmaceutically acceptable salts, such as, for example, a sulfonium salt, may be used, for example, The present invention is in the form of a single compound of the present invention and is included in the scope of the present invention. I and non-stoichiometric forms. Also included within the scope of the invention are all falling compositions, hydrates and complexes of the compounds and salts of the invention. Certain bases, substituents included in the invention , a compound or a salt, which may be present as an isomer. The invention in its scope includes all such isomers, including racemates, palmomerisomers and mixtures thereof. Certain bases in the salt, such as heteroaromatic rings, - or a plurality of tautomeric forms are present. Within the scope of the invention, all such tautomeric forms, including mixtures, are included. In particular, when intended for oral pharmaceutical use, the compound of formula (1) may optionally have a molecular weight of 1000. Or lower, such as 800 or lower, specifically 65 〇 or lower, or 600 or lower. The molecular weight here refers to the molecular weight of the unsolvated compound &quot;free base" compound, meaning Any molecular weight contributed by any addition salt, solvent (eg, water) molecules, and the like. Synthetic Method Pathways The following methods can be used to make the compounds of the invention:

Most of the following synthesis methods of R1 are examples of the compound of the formula 1 wherein R2 is a hydrogen atom (Η). However, the method of 邵, 邵, or 邵 邵 can also be used together with appropriate corrections such as starting material 87841-960303-中.doc-75-1283678 for the preparation of a compound of formula 1 wherein R2 is not ruthenium. .

Process A A compound of formula (I) wherein X = 0R5a can be obtained by formulating a compound of formula (9) according to the method described by Yu et al., J Λ^/C/zem., 2001, 44, 1025-1027. It is prepared by reacting an amine of R3NH2. This reaction is preferably carried out in the presence of a base such as triethylamine or N,N-diisopropylethylamine, and/or in an organic solvent such as ethanol, dioxane or acetonitrile. This reaction may require heating to, for example, about 60-10 (TC, such as about 80-9 (rc:

(I) The compound of the formula (π) is also described in the above reference, and can be reacted by heating a compound of the formula (ΙΠ) with, for example, diethyl ethoxymethylenemalonate (wherein R5a= Et) and heating , then reacted with phosphine chloride and heated again to produce:

Formula III 1)

In the case where the desired formula (III) is not commercially available (for example, R^CHJh), the preparation can be carried out by Dorgan et al. in 〇^红8〇(:., Perkin Trans. 1, (4), 938-42; The method described in 1980, by reacting cyanoethyl 87841-960303-medium doc-76-1283678 base with a suitable formula, in a solvent such as ethanol, and heating This is then achieved, for example, by reduction in a solvent such as a third-butanol. The r4 oxime should be chosen such that it will contain more than one carbon atom, for example an r4 group.

H2N

CN

1) R40CHO EtOH

2) Na / t-BuOH

Process B A compound of formula (I) wherein X = NR4R5 can be prepared by reacting a compound of formula (IV) with an amine of formula R3NH2. This reaction is preferably carried out in the presence of a base such as triethylamine or N,N-diisopropylethylamine, and/or in an organic solvent such as ethanol, THF, dioxane or acetonitrile. This reaction may require heating to, for example, about 60-100 ° C or about 80-90 ° C, for example over 8-48 or 12-24 hours:

The compound of formula (IV) can be prepared in two steps, as described by Bare et al., ju C7^w. 1989, 32, 2561-2573. This method first involves the compound of formula (v) and sulfinium dichloride (or another agent suitable for the formation of ruthenium chloride from tickic acid), whether in an organic solvent such as gas or THF, or Solvent solution reaction. This reaction may require heating, and the formation of 87841-960303-medium doc-77- 1283678 may or may not be separated. Step _ - In this T, it relates to the formula R4R5NH amine, in the organic solvent such as THF or chloroform, anti-deer, ^, T 夂 and yoke may involve a base, such as triethylamine or diisopropylethylamine use:

Formula V

The NFTR3 formula (V) can be produced by the hydrolysis of the formula (8) g according to the method described by Yu et al., V. 4, Hall 1027. Preferably, the procedure involves the reaction, such as the oxidation of steel or potassium hydroxide, in a solvent such as a waterborne agent such as aqueous ethanol or aqueous dioxin:

Process C The compound of formula (I) can also be prepared according to the method described by Bare et al., /C/zem. 1989, 32, 2561-2573, which relates to a compound of formula (VI) wherein -0 -R is -OA.4 alkyl, especially _〇_, reacted with an amine of the formula r3nh2. The reaction can be carried out with or without a solvent and may require heating. R\

R1

Formula VI

OR5a 87841_960303·中.doc -78- 1283678 The compound of formula (VI) (also described in the above references) can be prepared by reacting a compound of formula (VII) with a suitable alkylating agent of formula Ri-X, wherein X is a detached base, such as self-priming. This reaction should be carried out in the presence of a solvent such as potassium carbonate in an anhydrous solvent such as DMF:

OR

Formula VII

OR

R1-X K2C03 DMF The preparation of a compound of formula VII by oxidative cleavage of a compound of formula VIII

Bare et al. are described in MM. C/zem. 1989, 32, 2561-2573 (further according to Zuleski et al., J. Drug. Metab. Dispos., 1985, 13, 139).

Formula VIII

Formula VII Method D: To form a compound of formula (1) wherein X = NR4R5, a compound of formula (I), but wherein X = OH (carboxylic acid), can be converted to an activated compound of formula (I), but wherein X = The amine is substituted for the cleavage group; then, the activated compound can be reacted with the formula R4R5NH amine. For example, the activated compound can be cesium chloride, meaning an activated compound of formula (I), but wherein the cleavage group X = C1. It can be prepared from a carboxylic acid (X = OH), for example by reaction with thionous chloride. See, for example, Examples 81-85. Alternatively, the compound activated by 87841-960303-.doc-79-1283678 may be an activated ester wherein the cleavage group X is

The activated compound described later can be prepared from a carboxylic acid (χ = 0H), either: (8) by reacting a carboxylic acid with a carbodiimide such as EDC, which is 1-ethyl-3-(3-methylamino) Propyl)carbodiimide' and also 1-(3-dimethylaminopropyl)_3_ethylcarbodiimide or a salt thereof, such as the hydrochloride salt, followed by the resulting product and 1-hydroxybenzene And a triazole (HOBT) reaction; the reaction (4) is usually carried out in the presence of a solvent such as dimethylformamide (DMF), and/or usually at room temperature (for example, about 20 to about 25 ° C); ) via 2-(1H-benzotriazole small)-indole, iota, 3,3-tetramethylguanidine (TBTU) or hexafluorophosphate 0-(7.nitrobenzotriazole-1- Base)__,&gt;^,,&gt;1,-tetramethylguanidine (HATU) reaction, in the presence of a base, such as diisopropylethylamine (ipr^NetsDIPEA), and usually in the presence of a solvent, such as Dimethylformamide (DMF), and/or usually at room temperature (eg, from about 2 Torr to about 25 ° C). Accordingly, the present invention also provides a process for the preparation of a compound of formula (I) or a salt thereof, which comprises (a) a compound of formula (I) wherein X = OR5a is a reaction of a compound of formula (9) with an amine of formula R3NH2, or (b) With respect to the compound of the formula (1) wherein X = nr4r5 is a reaction of a compound of the formula (IV) with an amine of the formula R3NH2, or (c) a compound of the formula (VI) wherein an alkyl group is reacted with an amine of the formula r3; 87841-960303- .doc -80- 1283678 (d) is a compound of formula (I) wherein X = NR4R5, which is a compound of formula 1, but wherein X = OH (carboxylic acid), is converted to an activated compound of formula 1, but wherein X == a cleavage group which may be substituted by an amine (the activated compound may preferably be ruthenium chloride, meaning activated compound of formula (I), but X = C1), followed by activated compound and formula R4R5NH amine The reaction of the compound of formula (1), if appropriate, is converted to a salt, such as a pharmaceutically acceptable salt. Pharmaceutical Use The present invention also provides the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, as an active therapeutic substance in a mammal, such as a human. The compound or salt can be used to treat and/or prevent any of the symptoms described herein (eg, for use in treating and/or preventing inflammatory and/or allergic diseases in a mammal), and/or as a phosphodiesterase Inhibitors are used, for example, as phosphodiesterase 4 (PDE4) inhibitors. &quot;Treatment&quot; may include therapeutic treatment and/or prevention. Also provided is the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament, such as a pharmaceutical composition, in a mammal, such as a human. Treating and/or preventing inflammatory and/or allergic diseases. Also provided is a method of treating and/or preventing inflammatory and/or allergic diseases in a mammal, such as a human, in need thereof, including to a mammal ( For example, human) is administered a therapeutically effective amount of a compound of formula (1), or a pharmaceutically acceptable salt thereof, as defined herein. A bisphosphonate 4 inhibitor is believed to be useful in the treatment of mammals, such as humans. / or prevent a variety of diseases, especially inflammatory and / or allergic diseases, such as: asthma, chronic bronchitis, emphysema, atopic dermatitis, urticaria allergic rhinitis, allergic membranous inflammation, spring combined membrane Inflammation, addiction 87841-96〇3〇3-中.d〇c -81 - 1283678 Eosin granuloma, psoriasis, rheumatoid arthritis, septic shock, ulcerative colitis, Crohn's disease, myocardium and brain Reperfusion injury Chronic glomerulonephritis, endotoxin shock, adult dyspnea syndrome or multiple sclerosis. In the treatment and / or prevention, inflammatory and / or allergic diseases are preferably chronic obstructive pulmonary disease in mammals (such as humans) (c〇pD), asthma or allergic rhinitis. More preferably, it treats and/or prevents COPD or asthma in mammals such as humans. PDE4 inhibitors are considered to be effective for the treatment of asthma (see, for example, MAGiembyCZ, i&gt) ;., February 2000, 59(2), 193_212; Z-Huang et al., 荸4##之疔!庳, 2001, 5: 432-438; and references cited therein) and COPD (For example, see SLW〇Wa, Pregnancy 襄2〇00, 5(3), 309-319; Z·Huang et al., must learn to stand up and wear Longmo, 2001, 5: 432-438; And references cited therein.) c〇pD is usually characterized by the presence of airflow obstruction due to chronic bronchitis and/or emphysema (SLWolda, 2000). Pharmaceutical compositions and medications for medicine For the purposes of use, the compounds of the invention are usually administered in a pharmaceutical composition. In another aspect, the invention provides a pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers and/or excipients. The compounds can be used to treat and/or prevent any of the symptoms described herein. The compounds of formula (I) and/or pharmaceutical compositions can be administered, for example, orally, parenterally (eg, intravenously, subcutaneously or intramuscularly), inhaled or nasally. According to the administration method, 87841-960303-中.doc-82- 1283678 Therefore, the pharmaceutical composition is preferably suitable for oral administration, oral administration by mu, and parenteral (for example, the intravenous composition of the head is better, for example, for breastfeeding. Animals such as human inhalation, you, stop a orally. Inhaled dosing #, as well as topical administration to the lungs, for example by iin called milk, gelatin or dry powder compositions. Oral administration to humans is optimal. A pharmaceutical composition suitable for oral administration may be a liquid or a solid; for example, it may be a syrup, a suspension or an emulsion, a tablet, a capsule or a key. A liquid formulation will generally comprise a suspension or solution of such a compound or a pharmaceutically acceptable salt in a suitable pharmaceutically acceptable liquid carrier, such as an aqueous solvent such as water, ethanol or glycerol, or nonaqueous A solvent such as polyethylene glycol or oil. The formulation may also contain suspending agents, preservatives, flavoring and/or coloring agents. A pharmaceutical composition suitable for oral administration and in the form of a tablet may comprise one or more pharmaceutically acceptable carriers and/or excipients suitable for the preparation of a tablet formulation. Examples of such carriers include lactose and cellulose. Tablets may also or alternatively contain one or more pharmaceutically acceptable excipients such as binders, lubricants, such as magnesium stearate, and/or tablet disintegrants. A pharmaceutical composition suitable for oral administration and in capsules can be prepared using an encapsulation procedure. For example, a pellet containing the active ingredient can be prepared using a suitable pharmaceutically acceptable carrier and then filled into a hard gelatin capsule. Alternatively, the dispersion or suspension may be prepared using any suitable pharmaceutically acceptable carrier, for example, a hydrocolloid or oil&apos; and then the dispersion or suspension is filled into a soft gelatin capsule. Preferably, the compositions are in unit dosage form, such as tablets or capsules for oral administration, for example, for oral administration to humans. 87841-960303-中.doc-83- 1283678 The parenteral composition can comprise a solution or suspension of the compound or pharmaceutically acceptable salt in a sterile aqueous carrier or parenterally acceptable oil. Alternatively, the solution may be lyophilized; the lyophilized parenteral pharmaceutical composition may be reconstituted with a suitable solvent just prior to administration. Compositions for nasal or inhalation administration may conveniently be formulated as aerosols, drops, gels or dry powders. Aerosol formulations, for example for administration by inhalation, may comprise a solution or suspension of the active substance in a pharmaceutically acceptable aqueous or nonaqueous solvent. The aerosol formulation can be presented in a single or multiple doses in sterile form in a sealed container. The gastric container can be in the form of a cartridge or refill for use with an atomizing device or aspirator. Alternatively, the sealed container may be a single-distribution device, a single-dose nasal inhaler or an aerosol dispenser with a metering valve (a metered dose inhaler) - once the contents of the container have been exhausted, It is intended to be abandoned. In the case where the dosage form comprises a gas-filled gel or a mouth-washing/repairing knife, it is preferred to contain a "proper propellant" such as compressed air, carbon dioxide, or an organic propellant such as chlorofluorocarbon under pressure (for example). CFC) or hydrofluorocarbon (HFC). Suitable CFC propellants include dichlorodifluoromethane, - &gt; difluorofluoromethane and dichlorotetrafluoroethane. Suitable HFC propellants include '', 2,3,3,3-heptafluoropropane and m2-tetrafluoroethane. The gas can be held in the form of a Γ 杈 泵 pump _ atomizer. Preferably, the β-form (I) hydration or salt is in a reduced particle size, and the reduced size is better in the form of a medicinal composition for inhalation administration. Obtained or obtained by the use of granules. Micronization typically involves the application of a frictional compound/salt in a fast flowing annular/closed path air stream that often contains a cyclone assembly 87841-960303-^.doc-84- 1283678. The particle size (e.g., D50 value) of the compound or salt of reduced size (e.g., micronized) is preferably from about 0.5 to about 10 microns, such as from about 1 to about 5 microns (e.g., when using laser diffraction metrics). For example, the compound or salt of formula (I) preferably has a particle size as defined below: D10 is from about 0-3 to about 3 microns (e.g., about 1 micron), and/or D50 is from about 1 to about 5 microns (e.g., about 2). -3 microns), and/or D90 is from about 3 to about 10 microns (e.g., about 5-6 microns); for example when using a laser diffraction metric. Examples of preferred micronization methods are now given instead of limitations: Micronization Example: Micronization of Example 518 or 518A • Purpose: To utilize the Jetpharma MCI micronizer to give an example of 518 or 51 δ 600 of about 600-1000 mg (after Said) micronization. • Analysis of the particle size of the parent (unmicronized) and micronized material by laser diffraction and analysis of crystallinity by PXRD. Equipment and Substance Equipment/Substance JetpharmaMCl Micronizer Analytical Balance Upper Filler Balance Numerical Caliper Vibrating Scraper Substances to be micronized Procedure: Description and Specifications Indiscriminate supply · Air tank barrels with 275 psi rate fittings

Sartorius analysis

Mettler PM400 VWR Electronic Caliper

Auto-spat splitter

Example 518 or 518A assembled the micronizers together. The distance from the thin waist of the input port will be adjusted to 1.0 cm each and measured with a micro caliper to determine that it has been properly inserted. Adjust the ring (R) and the waist (V) pressure according to the value specified in the experimental design 87841_96〇3〇3_.doc -85-1283678 (refer to the experimental paragraph below) by adjusting the micronizer Air valve on the pressure gauge. Check for leaks by observing any fluctuations in the pressure gauge readings. It should be noted that the pressure of the waist (7) is kept at least 2 bar above the ring (R) pressure to prevent backflow of material. Check the balance performance with the calibration code. Reset the specified amount of parent material (see the experimental operating section) to a plastic weighing boat. The material is then fed into the micronizer using a vibratory spatula at a specified feed rate. Material feed time and equipment pressure are monitored during the micronization process. Upon completion of the micronization operation, the nitrogen supply is turned off and the collection bag is tapped to allow the particles to settle into the recovery vessel at the bottom of the micronizer. Remove the collection bag and set aside. The micronized powder on the recovery vessel and cyclone (above the recovery vessel) was individually collected into different weighed + labeled collection vials. i has recorded the weight of the micronized material. The micronizer was disassembled, and the residual PDE4 compound on the inner surface of the micronizer was washed with 7 〇 / 3 〇 isopropanol / water and collected into a flask. The micronizer is then thoroughly cleaned by rinsing, rubbing with a suitable solvent, and drying before proceeding. Experimental operation of the parent (not micronized) substance · Example 518 or 518A used in the balance · Sartorius analysis of the fine waist outlet insertion depth: 1 〇 · 〇 mm operation # material delivery waist (V) / intended to feed Actual intake (g) ring (R) pressure feed rate time feed rate (bar) (minutes + seconds) (g / min) 1 0.8795 g V = 10 bar 200 mg 4 minutes 51 〇 · 181 g / -86- 87841-960303-中.doc 1283678 R = 6 bar/minute second minute result and / or observation / yield - [(material from the container + material input from the cyclone)] Using this method, a yield of very close to 7〇% can be achieved. Alternative Embodiments Examples of the compounds/salts of the invention other than Example 518 or S1SA can be micronized. Suitable and/or compatible for inhalation administration In the case of a pharmaceutical composition, the pharmaceutical composition is preferably a dry powder inhalable composition. Such a composition may comprise a powder base such as lactose or starch, a compound of formula (I) or a salt thereof (preferably having a reduced particle size) Form, for example in micronized form, and a performance change A granule, such as L-leucine, mannitol, trehalose and/or magnesium stearate. The dry powder inhalable composition preferably comprises a dry powder blend of lactose with a compound of formula (1) or a salt thereof. It is a lactose hydrate such as lactose monohydrate' and/or preferably inhaled grade and/or fine grade lactose. The particle size of lactose is preferably defined as 90% or more (weight ratio or volume ratio) of lactose. The particles are less than 1 micron in diameter (eg, 10 to 1000 microns, such as 3 to 1000 microns), and/or 50% or more of the lactose particles are less than 5 microns in diameter (eg, 10-500 microns). Lactose. Preferably, the particle size is defined as 9% or more of the lactose particles being less than 300 microns in diameter (eg, 10-300 microns, such as 50-300 microns), and/or 50% or more of the lactose particles in diameter. Less than 100 microns. The particle size of lactose is defined as 90% or more of the lactose particles being less than 100-200 microns in diameter, and/or 50% or more of the lactose particles being less than 40-70 microns in diameter. Importantly, preferably from about 3 to about 30% (e.g., about 10%) (by weight or The volume ratio of the particles is less than 50 microns or less than 87841-960303 - medium .doc -87 - 1283678 20 microns diameter. For example, but not by limitation, the appropriate inhalation grade lactose is E9334 lactose (10% fine powder XBorculoDomo Ingredients, Hanzeplein 25, 8017 JD Zwolle,

Netherlands) o In a dry powder inhalable composition, the compound of formula (1) or a salt thereof is preferably from about 0.1% to about 70% by weight of the composition (e.g., from about 1% to about 50%, such as from about 5% to about 40%). , for example, from about 20 to about 30%) is present. Illustrative, but non-limiting examples of dry powder inhalable compositions are as follows: Dry Powder Formulation Example - Dry Powdered Lactose Blend Preparation The use of a compound of formula (I) or a salt thereof in reduced size, eg, micronized form (eg, in the above micronized example) The dry powder blend is obtained by adding the required amount of the compound/salt (for example, 10 mg, 1% w/w) to the inhaled grade lactose containing 10% of the fine powder (for example, 990 mg, 99% w /w), in a Tefl〇nTM (polytetrafluoroethylene) canister, in a Mikro-decomposer ball mill (but without a ball) at 3/4 speed (about 2000-2500 rpm) in each blend It was prepared by mixing for about 4 hours at a concentration. The Mikro-Decomposer ball mill (without the ball) (available from B. Braun Biotech International &amp; 3, Schwarzenberger Weg 73-79, D-34212 Melsungen, Germany; www.bbraunbiotech.com) contains a base with a TeflonTM canister The connection protrudes upward and the side can vibrate the arm. The vibration of this arm will achieve blending. Other blends·· 10% w/w compound/salt (50 mg) + 90% w/w lactose (450 mg, inhaled lactose, containing 10% fine powder). Serial dilutions of the 1% w/w blend can achieve, for example, 0.1% and 0.3% w/w blends. 87841-960303-中.doc -88 - 1283678 Depending on the circumstances, particularly for dry powder inhalable compositions, the pharmaceutical composition for inhalation administration can be incorporated into a plurality of sealed dose containers (e.g., containing a dry powder composition). It is loaded longitudinally into a strip or tau inside the appropriate inhalation device. The container is rupturable or peelable open, as desired, and for example, the dosage of the dry powder composition can be dosed via a device, such as a DISKUSTM device sold by GlaxoSmithKline. The diskustμ inhalation device is generally substantially as described in (3) 82, 242, 134. In such a device, at least one container of the pharmaceutical composition in powder form (these are preferably more than J devices) a sealed dose container, longitudinally loaded between the strips or strips, defined between two peelable members that are secured to each other, the device comprising: a setting defining an opening position of the at least one container The opening position is used to separate the members apart to open the container; and an outlet is communicated with the opened container, through which the user can inhale the pharmaceutical composition in powder form from the opened container. Or one or each dosage unit for oral or parenteral administration, preferably containing from 0. 01 to 3 mg, more preferably from 5 to 1 mg of the compound of formula (I) or A pharmaceutically acceptable salt, calculated as a free base. One or each dosage unit for nasal or inhalation administration, preferably containing from 0.001 to 50 mg, more preferably from 0.01 to 5 mg of the compound of formula 1 A pharmaceutically acceptable salt thereof, calculated as a free base. The pharmaceutically acceptable compound or salt of the present invention is preferably administered in a daily oral or parenteral dose of from 0.001 mg to 5 mg per kg of body weight per day. (mg/kg/day), for example 0.01 to 20 mg/kg/day, or 〇〇3 to 10 mg/kg/day, or 0.1 to 2 mg/kg/day of the compound of formula 1 or its pharmacy 87841-96〇 In 3〇3_, d〇c -89-1283678 The acceptable salt 'is calculated as a free base and administered to a mammal (for example, a human). The pharmaceutically acceptable compound or salt of the present invention is preferably the following A daily nasal or inhaled dose is administered to a mammal (eg human): 〇〇〇〇1 to 5 mg/kg/day, eg 0.001 to 1 mg/kg/day, or 〇005 to 〇3 mg/kg/day A compound of the formula (I) or a pharmaceutically acceptable salt thereof, calculated as a free base. The pharmaceutically acceptable compound or salt of the present invention is preferably administered in a daily dose to an adult patient. For example, an oral or parenteral dose of 3,000 mg per day or 5 to 1 per day 〇〇〇mg, for example, 2 to lion 2 per day, or nasal or inhaled dose of 1 to 3 mg per day or 1 to % pg per day or 0. 01 to 30 mg per day or daily A compound of formula 1 or a pharmaceutically acceptable salt thereof in an amount of from 1 to 5 mg, calculated as a free state. Combinations In accordance with the "compounds, salts and/or pharmaceutical compositions of the present invention, n therapeutically active agents may also be used in combination, for example, an amine, an antiallergic or an anti-inflammatory agent. Further, the present invention provides a compound or a pharmaceutically acceptable salt thereof, accompanied by another: a formula 1 deodorant or an anti-infective agent. % household "an example of a broad-adrenergic receptor stimulant, including Mmeterol" (for example, made as a foreign special isomer), and a sedative (salbut: U to an isomer) such as 舒舒(__ ), 弗莫87841 -960303 -中.doc -90- 1283678 Mo (salmefamol), fentanol or osmectin, and its salts, such as salbutol (salmeterol) Salt, salbutamol sulfate or free state or fumarate fumarate. Long-acting-adrenergic receptor stimulant is preferred, especially for therapeutic effects over a 24-hour period For example, salmeterol or fluoterol. Preferred long-acting/32-adrenergic receptor agonists, including WO02/066422A, WO 03/024439, WO 02/070490 and WO 02/076933 The above-mentioned long-acting-adrenergic receptor agonist, including the compound of formula (XX) (described in WO 02/066422):

Or a salt or solvate thereof, wherein in the formula (XX): mx is an integer of 2 to 8; nx is an integer of 3 to 11, with the proviso that mx+nx is 5 to 19, and R11X is -XSC^NRMXrHX Wherein alkenyl; R16X and R17X are independently selected from the group consisting of hydrogen, Cu alkyl, c3-7 cycloalkyl, c(o)nr18Xr19X, phenyl and phenyl (Cl-4 alkyl)_, or R16X in combination with R17X and the like. The nitrogen, together formed, 6- or 7-membered nitrogen-containing ring, and R1 6X and R1 7X are each optionally substituted by one or two groups, the substituent being selected from a halogen group, (V6 alkyl, c!·6) _Alkyl, cv6 alkoxy, hydroxy substituted cw alkoxy, -C02R18X, _S02NR18XR19X, -conr18Xr19X, or 5_,6_ or 7-membered heterocyclic ring; 87841-960303-中.doc -91- 1283678 R18X Independently selected from the group consisting of hydrogen, Ci6 alkyl, C36 cycloalkyl, phenyl and phenyl (Ci_4 alkyl)-; and px is an integer from 0 to 6, preferably from 〇 to 4; R12X is independent of RUX It is selected from the group consisting of hydrogen, Ci6 alkyl, Ci6 alkoxy, dentyl, phenyl and Ci-6-alkyl; and R14X and R15X are independently selected from hydrogen and Ci 4 alkyl, with the proviso that rmx and R15X The total number of carbon atoms does not exceed 4. Revealed on W0 02/066422 Preferred sputum-adrenergic receptor motivators include: 3-(4_{[6-({(2R)-2-#f-based-2·[4-hydroxy-3-(methyl))- Phenyl]ethyl}amino)hexyl]oxy} butyl)benzene extender, with 3-(3_{[7-({(2R)-2-hydroxy_2-[4_hydroxy_3_ Hydroxymethyl)phenyl]ethyl}amino)heptyl]oxy}propyl)benzenesulfonamide. A preferred sputum-adrenergic receptor mobilizer disclosed in WO 03/024439 is 4-{(lR)_2-[(6_{2-[(2,6-dichlorobenzyl)oxy]] Ethoxy}hexyl)amine-based turtle ethyl}-2-(hydroxymethyl)phenol. Examples of antihistamines include mesapyriiene or lolatatin. In another aspect, the invention also provides a combination comprising a compound of formula 1, or a pharmaceutically acceptable salt thereof, with an anti-antibiotic Cholinergic compounds, such as muscarine (M) receptor antagonists, in particular, %, Mi/M2 or m3 receptor antagonists. For a combination of an anti-cholinergic compound/musbine receptor antagonist and a pDE4 inhibitor, see, for example, W〇〇3/〇11274A2 and w〇〇2/〇69945 A2 / US 20〇2/〇193393 A1 and US 20 〇 2/052312 A1, and some or all of these publications are given anticholinergic 8784·1960303-medium doc-92- 1283678 compound/fly that can be used with the compound or salt of formula 1 An example of a muscarinic receptor antagonist. Other suitable combinations include, for example, other anti-inflammatory agents such as NSAIDs (eg, white triterpene antagonists, iNOS inhibitors, tryptase and elastase inhibitors, /3-2 integrin antagonists, and adenosine 2a agonists) or Prevent infectious agents (such as antibiotics, antiviral agents). The combination referred to above may conveniently be presented in the form of a pharmaceutical composition for use, and thus, a pharmaceutical composition comprising a combination as defined above, along with one or more pharmaceutically acceptable carriers and/or Or an excipient, representing another aspect of the invention. The individual compounds of such combination may be administered in separate or combined pharmaceutical compositions, either sequentially or simultaneously. Biological Test Methods PDE 3, PDE 4B, PDE 4D, PDE 5, PDE 6 Preliminary Detection Methods The activity of the compounds can be measured by the detection methods shown below. Preferably, the compound of the invention is a selective PDE4 inhibitor, meaning that it inhibits PDE4 (e.g., PDE4B and/or PDE4D, preferably PDE4B) more strongly than it inhibits PDE3, and/or is more potent than its inhibition of PDE5, and / or more intense than its inhibition of PDE6. PDE enzyme source and literature reference human recombinant PDE4D, especially its 2B junction variant (HSPDE4B2B), is revealed in W0 94/20079, and MM McLaughlin et al., &quot;low Km from human brain, rolipram (rolipram)-sensitive, cAMP-specific phosphodimerase: asexual reproduction and expression of cDNA, biochemical characteristics of recombinant proteins, and tissue distribution of mRNA&quot;, /· 5zW· C/zem·, 1993 , 268, 6470-6476. The human recombinant PDE4B line is expressed in the PDE-deficient Saccharomyces cerevisiae strain 87841-960303-中.doc-93- 1283678 GL62. The 100,000 gram supernatant of the yeast cell lysate is used for PDE4B detection and inhibitor studies. The human recombinant PDE4D (HSPDE4D3A) line, disclosed in P. A. Baecker et al., will separate the cDNA encoded by the human rolipram-sensitive cyclic AMP phosphodiacetase (PDEIVD). (3⁄4? 1994, 138, 253_256. The human recombinant PDE5 line is disclosed in K. Loughney et al., the individualization and characterization of the cDNA encoded by PDE5A, a human cGMP-binding, cGMP-specific 3', 5f-cyclic nucleotide phosphodiesterase '', 1998, 216, 139-147. PDE3 is novel, effective and specific according to H. Coste and P. Grondin, &quot; type V phosphodiesterase Inhibitors were characterized by Liding'', P/zarmaco/, 1995, 50, 1577-1585, purified from bovine aorta. PDE6 was purified from bovine retina as described below: P. Catty and P. Deterre , "Retina cGMP-specific citrate diesterase activation and solubilization by limited proteolysis", five wr · · · · 1991, 199, 263-269; A · Tar et al π bovine retinal cGMP Purification of phosphodiesterase π, recorded method, 1994, 238, 3-12; and / or D · Srivastava et al. The role of cyclic GMP hydrolysis of bovine retinal rod cyclic GMP phosphodiesterase '', oc/zem. human 1995, 308, 653-658. PDE 3, PDE 4B, PDE 4D, PDE S or PDE 6 activity The ability of the inhibitory compound to inhibit catalytic activity in PDE4B or 4D (human recombinant), PDE3 (from bovine aorta), PDE5 (human recombinant) or PDE6 (from bovine retina) in the 96-well format By scintillation proximity detection (SPA) determination, the test compound is allowed to be at ambient temperature (room temperature) on the Wallac isoform plate (generation 87841-96〇3〇3-medium.doc-94-1283678 code 1450-514) In the middle, 5:111]\0^-11 (:1 buffer (?117.5), 8.3111]^1^(:12, 1.7 mM EGTA, 0.05% (w/v) PDE enzyme in bovine serum albumin, Pre-culture logo minutes (usually 30 minutes) Adjust the enzyme concentration so that during the culture, in the control well without compound, the hydrolysis defined below does not exceed 20% hydrolysis. Detection of PDE3, PDE4B and PDE4D , adding [5f,8-3H] gland phenanthrene 3'5'_ cyclic phosphate (Amersham Pharmacia Biotech, code TRK.559), obtained each 0.05 uCi, and the final concentration ~ΙΟηΜ. For PDE5 and PDE6 assays, [8-3H] guanine riboside 31, cyclic phosphate (Amersham Pharmacia Biotech, code TRK.392) was added to obtain a final concentration of 0.05 uCi per well and ~36 nM. The plates were mixed on an orbital shaker for 5 minutes and incubated for 1 hour at ambient temperature. Phosphodiesterase SPA beads (Amersham Pharmacia Biotech, code RPNQ 0150) were added (~1 mg per well) to stop the assay. The plate is sealed and shaken and allowed to stand at ambient temperature for 35 minutes to 1 hour (preferably 35 minutes) to allow the beads to settle. The combined radioactive product was measured using a WALLAC TRILUX 1450 Microbeta scintillation counter. Ten concentrations of each compound (L5nM - 30 uM) were tested to provide a inhibition curve. The curves were analyzed using ActivityBase and XLfit (ID Business Solutions, Inc.). The results are based on the PIC 〇 value table TF. The biological data obtained for some of the examples (PDE4B inhibitory activity, either a reading or an average of about 2-6 readings) are as follows, based only on current metrics. Absolute accuracy is not possible and the readings are only accurate up to approx. ± 0.5 log units, depending on the number of readings performed and averaged: Example number PDE4B pIC5〇2 8.0 3 7.8 87841-960303-medium. Doc -95- 1283678 6 6.6 11 7.4 21 8.5 22 7.9 32 7.7 40 8.3 63 6.9 1,36, 39, 41,42, 43, 44, 47, 48, 63, 83, 109, 178, 187 and 600 7.0 7.9 100, 155, 165, 167, 201, 260, 261, 263, 265, 266, 267, 271, 493, 494, 495, 498, 518, 518A, 551, 575, 581, 584, 619, 622, 624- 626, 628, 630, 636, 638, 643-645 and 653 8.2 to 9.6 196 7.9 198 8.5 Excluding reference examples 19-20, these examples have PDE4B inhibitory activity at pICs 0 = about 5·5 (earth 〇·5 ) to a range of approximately 9.6 (about 0. 5). The majority (about 95% or more) of the examples, excluding Reference Examples 19-20, have a PDE4B inhibitory activity in the range of from about 6 (about 〇·5) to about 9.6 (about 0.5). Wherein R3 = cyclohexyl (NHR3 = subtype (c)), tetrahydro-2H-piperazin-4-yl (NHR3 = group (h)), 4-ketocyclohexyl_3 = subtype (0) Or some other type of substituted cyclohexyl or some of the heterocyclic rings, when measured in the above enzyme inhibition assay, with a comparable example wherein R3 = cyclopropyl_3 = subformula (b)) Selective comparisons, usually or often (especially with respect to Rl = ethyl), have a higher degree of selectivity for PDE4B than PDE5. For example, it is based only on the current measurement and is subject to cumulative detection inaccuracy: 87841»960303^.doc •96- 1283678 - Examples 21, 4〇, 90, 19δ and 201 (where njjr3 is individual = subtype (h) , (c), 1, (8) and (ο), R1 = ethyl) have a selectivity for pDE4B over pDE5 'in about 3 to 20 or more times, more than R3 = cyclopropyl ( NHR3 = substrate (b)) is equivalent to the selectivity achieved by Example 39; - Examples 43 and 44 (where NHR3 is individual = subtypes (4) and (8)) have a selectivity over pDE5 for pDE4B, at about 4 to 8 or More than the range, more than equivalent R3 = selectivity achieved by cyclopropyl example 42; - Examples 22 and 48 (where NHR3 is individual = subtypes (8) and (c)) have a preference for pDE4B over PDE5 Sex, in the range of about 2.5 to 1 or more times, more than equivalent R3 = selectivity achieved by cyclopropyl example 47; and - examples 2 and 3 (where NHR3 is individual = subtypes (6) and (8)) The selectivity for pDE4B over PDE5 is greater than the equivalent of R3 = cyclopropyl Example 1 in the range of about 2 to 5 or more. Errata gel spit: Some known PDE4 inhibitors may cause vomiting and/or nausea, to a greater or lesser extent (see, for example, z·Huang et al., must learn to learn #学之疔疔, 2001, 5: 432-438, especially refer to page 433_434 and references cited therein). Therefore, if the pDE4 inhibiting compound or salt of the present invention causes only a limited or easy to treat vomiting side effect, it is preferred, but not essential. When ferrets are administered, the side effects of vomiting can be measured by, for example, the vomiting potential of the compound or salt; for example, we can measure vomiting, retching and vomiting in ferrets after oral or parenteral administration of the compound or salt. / or the time, privateness, frequency and/or duration of the warning. See, for example, A. Robichaud et al., 'Vegetation caused by [PDE IV] inhibitors in ferrets M, Neuropharmacology, 1999, 3 8, 289-297 87841-960303-中.doc-97- 1283678 2001, 40, 465-465. However, it is more preferred that the vomiting side effects and therapeutic index in the rats are administered after the administration of the compound or salt of the present invention, preferably by monitoring the eating behavior of the eclipse in the rats (see in vivo assay 2 below). It is true that some PDE4 inhibitors may cause other side effects, such as headaches and other side effects of the central nervous system (CNS-); and/or gastrointestinal (GI) disorders. Thus, it is preferred, but not required, that a particular PDE4 inhibiting compound or salt of the present invention will only result in limited or easy to treat side effects of one or more of these side effect types. In vivo biological assays The above-mentioned in vitro enzyme PDE4B inhibition assay should be considered as a preliminary test for biological activity. However, the following are other in vivo biological assays that are selected and are not a measure of efficacy or side effects. In vivo detection 1. LPS-induced pulmonary neutropenia in rats: oral administration of PDE4 inhibitors Lung neutrophil influx has been shown to be an important component of the pulmonary disease group, such as chronic obstruction Pulmonary disease (COPD), which may involve chronic bronchitis and/or emphysema (GF· Filley, 2000; 117(5); 251 s-260s). The purpose of this neutrophil model is to study the potential anti-inflammatory effects of dermal neutropenia caused by inhalation of aerosolized lipopolysaccharide (LPS) in the study of oral administration of PDE4 inhibitors. To make a model of neutrophil inflammatory components of COPD. For the scientific background, please refer to the following passages. Male Lewisian rats (Charles River, Raleigh, NC, USA) weighing approximately 300-400 grams, either as (8) suspended in water, 0.5% methylcellulose 87841-960303-medium.doc -98-1283678 ( The test compound was obtained from Sigma_Aldrich, St Louis, MO, USA), or (b) was pretreated with vehicle and delivered orally in a dose volume of 10 ml/kg. In general, dose response curves were generated using the following PDE4 inhibitor doses: 1 〇·〇, 2.0, 0.4, 0.08, and 0.016 mg/kg. Thirty minutes after pretreatment, the rats were exposed to aerosolized LPS (serotype E. coli 026 ··B6) produced by an atomizer containing 100 μg/ml LPS solution, prepared by a rat vinegar fel extract Cheng ' is available from Sigma_Aldrich, St Louis, MO, USA). At a rate of 4 liters per minute, the rats were exposed to a gas gel for 20 minutes. The LPS exposure was carried out in a closed chamber having an internal dimension of 45 cm length X 24 cm width x 20 cm height. The exposure chamber is contained in a certified ventilated fume hood. After 4 hours of exposure to Lps, 'at 90 mg/kg', the dose is administered by intraperitoneal administration of excessive dose &lt; pentobarbital. Euthanasia. The tracheal trachea and lung lavage (BAL) were pre-formed through a 14-gauge blunt needle into an exposed trachea. Five 5 ml washes were performed to collect a total of 25 ml of BAL fluid. Total cells were injected into the BAL fluid. Count the difference from white blood cells to calculate the amount of neutrophil to the lungs. Calculate the percentage of neutrophil inhibition under each dose (see vehicle) and produce a variable slope, sigmoidal dose response curve, usually used PrismGraph-Pad. This dose response curve was used to calculate the value of 〇5〇 (expressed in milligrams per kilogram of body weight) for inhibition of LPS-induced neutropenia by pDE4 inhibitors. Based on the current metrics, the compounds of Examples 22 and (5) were administered orally in the above procedure, showing that neutropenia inhibits an ED50 value of from about 0.5 mg/kg to about 2 mg/kg. The range is 87841_96〇3〇3_中.doc -99- 1283678. In the alternative embodiment of this procedure, a single oral dose of 10 mg/kg is administered to the rats. Or 1.0 mg/kg of PDE4 inhibitor (or vehicle) and calculate percent neutrophil septicemia and report the specific dose. In this particular example, based on current metrics, Examples 21, 100, 109 Compounds of 167, 172 and 600, in the above procedure, administered orally at a single dose of L0 mg/kg, showing a percent inhibition of neutropenia, ranging from about 19% to about 69% Internal (or in the range of about 32% to about 69%, for examples 21, 100, 109, 167, and 600).

Filley G.F. Comparison of the structure and inflammatory characteristics of COPD and asthma. C% is .2000; 117(5) 251 s-260s.

Howell RE, Jenkins LP, Fielding LE and Grimes D· In the brown Norway rats, antigen-induced pulmonary eosinophilia and neutropenia are inhibited by selective inhibitors of phosphodiesterase types 3 and 4. · #桌理1995 ; 8 : 83-89.

Spond J, Chapman R, Fine J, Jones H, Kreutner W, Kung TT? Minnicozzi, M. Comparison of PDE4 inhibitors, rolipram and SB207499 (ArifloTM) in the rat model of pulmonary neutropenia摩桌理#和治# #.2001 ; 14 ·· 157-164 〇

Underwood DC, Osborn RR? Bochnowicz S5 Webb EF, Rieman DJ, Lee JC, Romanic AM, Adams JL, Hay DWP and Griswold DE. SB 239063, p38MAPK inhibitors reduce neutrophils, inflammatory cytokines in the lungs, 87841-960303-中.doc -100- 1283678 MMP-9 and fibrosis·^/corpse Cfe&quot; M^/ household////〇/. 2000; 279: L895-L902. In vivo detection 2. The sputum of the white rat heterotrophic sputum mode f # · · Selective PDE4 inhibitor, has increased cAMP by many immune cells (such as lymphocytes, single cells) in various in vitro and in vivo modes The intracellular content has been shown to inhibit inflammation. However, some of the side effects of pDE4 inhibitors in many species are vomiting. Since many of the inflamed large white gas patterns are well characterized, they have been used in procedures (see, for example, in vivo assay 1 above) to confirm the beneficial anti-inflammatory effects of PDE4 inhibitors. However, the rats did not respond to vomiting (there was no vomiting reflex), making it difficult to study the relationship between the beneficial anti-inflammatory effects of PDE4 inhibitors and vomiting directly in rats. However, in 1991, Takeda et al. (see the passage below) confirmed that the eclipse feeding response in rats was similar to vomiting. In white mice, there is a response to the behavior of the disease, in which large μ is a feeding material, such as soil or especially clay (such as kaolin), which can help and collect the parent. Eating with different foods can be achieved by exercise and chemicals (especially in the human body, spitting chemistry (1), and can make riding in the human capital to suppress the singer "drugs", music theory, inhibition. In vivo detection 2, can determine the degree of response to PDE4 inhibition of ecstasy in rats at pharmacologically relevant doses, anti-inflammatory test (such as the above live-group) in vivo in the mouse m tongue 1 &quot; The internal detection G is carried out in parallel. In the same species, the detection of the canine and the eclipse can be used to provide the therapeutic index of the compound/salt of the invention in the white rat (于). White sputum can be, for example, 87841-96〇3〇3·中.doc -101-1283678. The potential vomiting of the self-test 2 is ED5〇 dose, and b) the dose of anti-inflammatory ED50 of the mouse (for example, by in vivo detection 1) The ratio of the neutropenia inhibition measure in rats is calculated by the fact that at many anti-inflammatory doses, a larger TI ratio may indicate lower vomiting. This may allow for the anti-inflammatory effects of the compounds or salts of the present invention. Cause spitting or minimal vomiting The choice of dosage is. However, it should be understood that it is not necessary to achieve a low vomiting PDE4 inhibitory compound. On the first day of the experiment, the rats were individually housed in a cage without a tiling or π reinforcement. The rat is kept away from the cage floor by a metal mesh. A pre-weighed food cup containing standard rat food and clay granules is placed in a cage. Clay available from Languna Clay Company (Industrial City, CA, USA) The granules are the same size and shape as the food granules. The rats are adapted to the clay for 72 hours. During this time, the cups and foods from the cage are weighed daily on an electronic balance that can be measured to the nearest 0.1 gram. Clay debris. At the end of the 72-hour adaptation period, the rats generally showed no interest in clay granules. At the end of 72 hours, the rats were placed in clean cages and the food cups were weighed. The mice that consumed the clay were removed from the study. Just before the dark cycle (the animal is active and should be eating), the animals were divided into several treatment groups and orally With the dose of the compound/salt of the present invention (different doses of different treatment groups) or a separate vehicle at a dose volume of 2 ml/kg, the compound/salt is 〇·5% methyl in water. The suspension in the form of vitamins (available from Sigma-Aldrich, St Louis, MO, USA). The next day, weighed the food and clay cups and cage debris, and calculated that every night was 87411-96〇3〇 D〇c -102- 1283678 The total amount of clay and food consumed by an animal. The dose response is calculated by first converting the data into a quantum response, in which the animal responds to the eclipse as either positive or negative. The consumption is more than the average calculated using the computational regression of the Statistica statistical suite software, greater than or equal to 0.3 grams of clay, and the rat is "pigmented 癖 positive π. The ED50 value of the eclipse can then be calculated and expressed in milligrams per kilogram body weight. Using the above procedure, and according to the current metric, the compounds of Examples 22, 83 and 155 show that the eclipse responds to an ED50 in the range of from about 4.8 mg/kg to greater than or equal to about 40 mg/kg. It can be seen that these ecstasy respond to the ED50 dose, which is higher than the ED50 value of the three cases of neutropenia (see above in vivo test 1), so that the therapeutic index in rats> 2. When by measuring 1+2 and measuring according to the current metric, at first glance it seems that the three instances have been reached. literature··

Beavo JA, Contini, Μ·, Heaslip, R.J. Multiple Cyclic Nucleic Acid Diterpenoids Mol Pharmacol. 1994; 46: 399-405.

Spond J5 Chapman R? Fine J5 Jones H3 Kreutner W, Kung TT5 Minnicozzi M. Comparison of PDE4 Inhibitor, Rolipram and SB207499 (ArifloTM) in Rat Model of Pulmonary Leukocytosis • Lung Pharmacology and Treatment Learning .2001 ; 14 : 157-164.

Takeda N, Hasegawa S, Morita Μ and Matsunaga T· White rats are similar to vomiting: animal model of vomiting research. Pharmacology, biochemistry and behavior. 1991; 45: 817-821. 87841-960303-中.doc -103- 1283678

Takeda N, Hasegawa S, Morita M, Horii A, Uno A, Yamatodani A and Matsunaga, 1&gt; The pharmacological mechanism of vomiting in the area · I. Antiemetic drugs in rats - exercise - and apomorphine - induced eclipse The role of 癖. C / as in 1995; 17 (9) 589-596.

Takeda N, Hasegawa S, Morita M, Horii A, Uno A, Yamatodani A and Matsunaga 1&gt; The pharmacological mechanism of vomiting in the area · II. The effect of antiemetics in rats on cisplatin-induced ecstasy · Mei/z Wm/Exp C7z&gt; 2 corpse/zarmaco/. 1995; 17(9)647-652. In vivo detection 3. Lung-induced neutropenia caused by LPS in rats · The effect of intratracheal administration of PDE4 inhibitor This test is inflammation in the lungs - specifically by lipopolysaccharide (LPS) An animal model of neutropenia that has been developed and allowed to investigate the putative inhibition (anti-inflammatory effect) of this neutrophilic leukemia by intratracheal (it) administration of a PDE4 inhibitor. Preferably, the PDE4 inhibitor is in the form of a dry powder or a wet suspension. Intratracheal administration is a mode of inhaled administration that allows local delivery to the lungs. Yu #: Male CDs (derived from Sprague Dawley) supplied by Charles River, Raleigh, NC, USA, in an array of 5 rats per cage, after delivery for at least 7 days, It is adapted to regularly replace the covering/habiting material, feeding the unrestricted SDS diet R1 granulated food, and supplying the daily replacement of pasteurized animal-grade drinking water. #粉授襄的袁I ·· After the use of the needle and the syringe, the 3-way interface is discarded. Weigh the 3-way sterile interface (Vycon reference 876.00), then add the drug blend or inhaled lactose (vehicle control) to the interface, close the 87841-960303-medium.doc-104-1283678 interface to prevent The drug is lost and the interface is weighed again to determine the weight of the drug in the interface. After the silk medicine, the p weight will be weighed again to determine the weight of the drug left in the interface. This needle, SigmaZ21934 々 syringe needle (9) number '152 mm (6 inches) long, with Luer's wheel hub, # is cut into approximately 毫米32 mm (5.2 ft) by engineering, made into a blunt end, Prevent it from damaging the trachea of the rats, and weigh the needle before and after the drug is delivered to confirm that no drug remains in the needle after taking the drug.涿 凭 凭 凭 凭 凭 凭 凭 凭 凭 . I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I . Table ####·························································· Inhibitors are used in the form of reduced size (e.g., micronized), for example, according to the micronization examples given above. For the dry powder administration of the drug, an example of a dry powder formulation of the above-mentioned drug and inhaled lactose may be used. The commonly used inhaled lactose (batch E98L4675 lot 845120) has 10% fine powder (1% by weight of material at a 15 micron particle size as measured by Malvern particle size). Wetting of the drug The suspension can be prepared by adding the required volume of vehicle to the drug; the vehicle used is a mixture of saline / Tween (0.2% Tween 80). The wetted suspension was sonicated for 10 minutes before use. Preparation and administration of pde4 inhibitor: post-tapping the 11-like meal in the rabbit plastic chamber and exposing it to isoflourane (4.5%), nitrous oxide (3 liters/min) and oxygen ( A gaseous mixture of 1 liter per minute was used to anesthetize the rats. Once anesthetized, the animals were placed in a stainless steel trachea on a drug carrying table. 87841_96〇3〇3_中.doc -105- 1283678 With its back, it is about 35. The corner is placed. Light the light at an angle to the outside of the throat to illuminate the air tube. Open the mouth and allow the opening of the airway to be seen. This procedure is as follows, the needle 'changes to the wet suspension of the PDE4 inhibitor and the dry powder administration: it is said to be wet and pregnant. · Through the needle of the metal medicinal drug that has been carefully inserted into the trachea of the rat, introduced Hold the sleeve. Animals were administered the vehicle or PDE4 inhibitor intratracheally via via needles with new internal cannulas for each of the different drug groups. Use a syringe attached to the medication needle to allow the formulation to slowly (10 seconds) to the trachea. The three-way interface device and the needle were inserted into the trachea of the rat to reach a predetermined point that was established to be positioned approximately 1 cm above the main bifurcation. Another operator holds the needle at the designated location while delivering milliliters of air through the three-way interface, via a pressurized syringe (ideally in line with the animal's inhalation), with the goal of expelling the entire amount of drug from the interface. After taking the drug, remove the needle and the interface from the airway and close the interface to prevent any residual drug from leaving the interface. After taking the drug, either wetted suspension or dry powder, the animal is then removed from the table and continuously observed until it has recovered from anesthesia. Return the animals to the containment cage and give them free access to food and water; observe them and note any unusual behavioral changes.镙虞到1····································································································· ML), after 15 minutes. The aerosol of Lps is produced by a nebulizer (DeVilbiSS, USA) and introduced into a transparent plastic exposure chamber. After the 15-minute LPS-exposure period, the animals were returned to accommodate the 87841·96〇3〇3_.doc -106 - 1283678 cage and allowed free access to food and water. [In an alternative embodiment, the rats can be exposed to LPS for less than 2 hours after administration in the trachea. In another alternative embodiment, the rats can be exposed to LPS for more than 2 hours (e.g., about 4 or about 6 hours) after intratracheal administration by vehicle or PDE4 inhibitor to test PDE4 inhibitors. Whether it has a long duration (this is not necessary)].犮扃f庳要过洗洗·· 4 hours after LPS exposure, the animals were killed by an overdose of sodium pentobarbitone (intraperitoneal cavity). The trachea was cannulated into a polypropylene tube and the lungs were lavaged (washed out) with 3 x 5 ml of hepatic lipidified (25 units/ml) phosphate buffered saline (PBS). Seto was centrifuged at 1300 rpm for 7 minutes from the white ▲ ball plus the sputum sputum. The supernatant was removed and the resulting cell pellet was resuspended in 1 ml of PBS. The cell slide of the resuspended fluid was prepared by placing 1 liter microliter of the resuspended BAL fluid into the cell rotation holder and then rotating at 5000 rpm for 5 minutes. The slides were air dried and then stained with Leishmans dye (20 minutes) to allow for differential cell counting. All cells were also counted from the resuspension. From these two counts, the total number of neutrophils in the BAL was measured. To measure inhibition by pDE4_inhibitors of neutrophilia, neutrophil counts were compared between vehicle-treated rats and PDE4 inhibitor-treated rats. A dose response curve can be generated by varying the dose of the PDE4 inhibitor used in the dosing step (e.g., down to 2 mg or 0.1 mg of PDE4 inhibitor per ounce of body weight, for example to 〇 mg/8 kg). All publications cited in this patent specification, including, but not limited to, the patents and the patent application Serial No. s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s The disclosures of each of the entire publications are hereby incorporated by reference herein in their entirety in the entireties in the the the the the the the the the the the While p ^ μ k this temple I is not intended to be construed as limiting the invention. In this paragraph, the synthesis of the intermediate compound in the middle ^. The combined use of the condensate used in this article · DCM dichloromethane EtOAc acetic acid Et20 ether

DMF MeOH dimethylformamide methanol HPLC high pressure liquid chromatography SPE solid phase extraction

Nuclear magnetic resonance (where: s = singlet, d = = doublet, t ~ one heavy peak, q = quadruple peak, dd = doublet - tongue you - 1 heavy peak, multiple peak, H = number of protons)

LCMS TLC liquid chromatography / mass spectroscopy thin layer chromatography

BEMP 2-Tertiary-butylimido·2·diethylamino]Less dimethylhydrogen 1,3,2-«—Nitrogen gambling 87041-960303-中.doc -108 - 1283678 EDC l- (3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride HATU hexafluorophosphate-(7-azobenzotriazole small)-N,N,N',N'- Tetramethyl hydrazine HBTU bismuth hexafluorophosphate-(benzotriazole small group)_N,N,N',N'-wT*# HOBT hydroxybenzotriazole h hour DIPEA diisopropylethylamine (iPr2NEt) Tret Residence time THF tetrahydrofuran

Lawesson's reagent 2,4-bis(4-methoxyphenyl)_1,3·dithio-2,4-diphosphonium tetraindole-2,4-disulfide is usually at room temperature of from about 20 to about 25°. Mechanical methods used herein within the scope of C: lcms (liquid chromatography / mass spectroscopy)

Waters ZQ mass spectrometer operating in positive ion electrospray mode with mass range 100-1000 amu UV wavelength: 215-330 nm

Column: 3.3 cm x 4.6 mm id, 3 μm ABZ + PLUS Flow rate: 3 ml/min Injection volume: 5 μl Solvent A: 95% acetonitrile + 0.05% formic acid solvent B: 0.1% formic acid + 10 mmol Ear concentration ammonium acetate gradient: 〇% A/0.7 minutes, 0-100% A/3.5 minutes, 100% A/U minutes, 100-0 % A/0.2 minutes

The quality-guided preparative HPLC 87841-96〇3〇3_中.doc -109- 1283678 The preparatory column used is Supelcosil ABZplus (10 cm χ 2·12 cm) (usually 10 cm χ 2·12 cm micron) UV wavelength: 200-320 micrometers Flow: 20 ml/min Injection volume: 1 ml; or better 0.5 ml solvent A: 0.1% formic acid solvent B: 95% acetonitrile + 5% formic acid; or more usually 99.95% acetonitrile + 0.05% formic acid gradient: 100% A/1 min, 100-80% A/9 min, 80-1% A/3.5 min, 1% A/1.4 min, MOO% A/0.1 min Intermediate 舆 Example Reagents not detailed in the following texts are commercially available from established suppliers such as Sigma-Aldrich. The addresses of the suppliers of the starting materials mentioned in the following intermediates and examples are as follows:

-ABCR GmbH, KG, P.O. Box 21 01 35, 76151 Karlsruhe, Germany - Aceto Color Intermediates (catalog name), Aceto, One Hollow Lane, Lake Success, NY, 11042-1215, USA

-Acros Organics, Division of Fisher Scientific, 500 American Road, Morris Plains, NJ 07950, USA -Apin Chemicals, 82 C Milton Park, Abingdon, Oxon 0X14 4RY, United Kingdom -Apollo Scientific, Unit 1A, Bingswood Industrial Estate, Whaley Bridge,

Derbyshire SK23 7LY, United Kingdom

Aldrich (catalog name), Sigma-Aldrich, Dorset, United Kingdom, electric 87841-960303-medium.doc-110- 1283678 words: +44 1202 733114; Fax: +44 1202 715460; [email protected]; Or - Aldrich (catalog name), Sigma-Aldrich, PO Box 14508, St. Louis, MO 63178-9916, USA; telephone: 314-771-5765; fax: 314-771-5757; [email protected]; Or - Aldrich (catalog name), Sigma Aldrich ChemieGmbh, Munich, Germany; Tel: +49 89 6513 0; Fax: +49 89 6513 1169; [email protected].

-Alfa Aesar, A Johnson Matthey, 30 Bond Street, Ward Hill, MA 01835-8099, USA - Array Biopharma, 1885 33rd Street, Boulder, CO 80301, USA - AstaTech, 8301 Torresdale Ave" 19C, Philadelphia, PA 19136, USA - Austin Chemical Company, 1565 Barclay Blvd,, Buffalo Grove, IL 60089, USA - Avocado Research, Shore Road, Port of Heysham Industrial Park, Heysham Lancashire LA3 2XY, United Kingdom -Bayer AG, Business Group Basic and Fine Chemicals , D-513 68 Leverkusen, Germany

Berk Univar plc, Berk House, POBox 56, Basing View, Basingstoke, Hants RG21 2E6, United Kingdom - Butt Park, Braysdown Works, Peasedown St. John, Bath BA2 8LL, United Kingdom - Chemical Structure Unit (catalog name), Ambinter, 46 quai Louis Bleriot, Paris, F-75016, France -ChemBridge Europe, 4 Clarkfs Hill Rise, Hampton Wood, Evesham, Worcestershire WR11 6FW, United Kingdom

-ChemService, P.O.Box 3108, West Chester, PA 19381, USA 87841-960303-中.doc -111- 1283678

-Combi-Blocks, Inc., 7949 Silverton Avenue, Suite 915, San Diego, CA 92126, USA - Dynamit Nobel GmbH, Germany; also available from: Saville Whittle Ltd (UK agents of Dynamit Nobel), Vickers Street, Manchester M40 8EF, United Kingdom -E. Merck,Gennany; or E. Merck (Merck Ltd), Hunter Boulevard, Magna Park, Lutterworth, Leicestershire LEI7 4XN, United Kingdom

_ Esprit Chemical Company, Esprit Plaza, 7680 Matoaka Road, Sarasota, FL 34243, USA - Discovery Library (catalog name), Ambinter, 46 quai Louis Bleriot, Paris, F-75016, France - Fluka Chemie AG, Industriestrasse 25, PO Box 260, CH-9471 Buchs, Switzerland -Fluorochem Company, Wesley Street, Old Glossop, Derbyshire SK13 7RY, United Kingdom

-ICN Biomedical Company, 3300 Hyland Avenue, Costa Mesa, CA 92626, USA - Interchim Intermediates (catalog name), Interchim, 213 Avenue Kennedy, BP 1140, Montlucon, Cedex, 03103, France Key Organics, 3, Highfield Indusrial Estate , Camelford, Cornwall PL32 9QZ, United Kingdom

Lancaster Synthetic Company, Newgate, White Lund, Morecambe, Lancashire LA3 3DY, United Kingdom -Manchester Organics, Unit 2, Ashville Industrial Estate, Sutton Weaver, Runcorn, Cheshire WA7 3PF, United Kingdom 87841-960303-中.doc -112- 1283678 -Matrix Scientific,Ρ·0· Box 25067, Columbia, SC 29224-5067, USA -Maybridge Chemical Company, Trevillett, Tintagel, Cornwall PL34 OHW,United

Kingdom -Maybridge Reactive Intermediate (catalog name), Maybridge Chemical Company, Trevillett, Tintagel, Cornwall PL34 OHW, United Kingdom - Microchemical Structure Unit (catalog name), MicroChemistry-RadaPharma, Shosse Entusiastov 56, Moscow, 111123, Russia - Miteni SpA, Via Mecenate 90, Milano, 20138, Italy -ND· Zelinsky Institute, Organic Chemistry, Leninsky prospect 47, 117913 Moscow B-334, Russia

-Optimer structural unit (directory name), Array BioPharma, 3200 Walnut Street, Boulder, CO 80301, USA -Peakdale Molecular &amp; 3, PeakdaleSciencePark, SheffieldRoad, Chapel-en-le-Frith, High Peak SK23 0PG, United Kingdom -Pfaltz &amp; Bauer, 172 East Aurora Street, Waterbury, CT 06708, USA - Rare Chemicals (Catalogue Name), Rare Chemicals GmbH, Schulstrasse 6, 24214 Gettorf, Germany - SALOR (Catalogue Name) (Sigma Aldrich Rare Chemicals Database) ), Aldrich Chemical Company, 1001 West Saint Paul Avenue, Milwaukee, WI 53233, USA - Sigma (catalog name), Sigma-Aldrich, PO Box 14508, St. Louis, MO 63178-9916, USA; see above for &quot Other non-US addresses and other contact details of Aldrich" - SIGMA-RBI, One Strathmore Road, Natick, ΜΑ 01760-1312, USA -Synchem OHG Heinrich-Plett-Strasse 40, Kassel, D-34132, Germany 87841-960303-中.doc -113- 1283678 -Syngene International Pvt &amp; 3, Hebbagodi, HosurRoad, Bangalore, India·

-TCI America,9211 North Harborgate Street, Portland, OR 97203, USA -TimTec Structural Unit Eight, 111111^, 111〇.,? 0 8〇父8941,\6\¥&amp;±, 0£19714-8941,USA

-Trans World Chemicals, 14674 Southlawn Lane, Rockville, MD 20850, USA Fine Ubichem PLC, Mayflower Close, Chandlers Ford Industrial Estate, Eastleigh, Hampshire S053 4AR, United Kingdom - Ultrafine (UFC), Synergy House, Guildhall Close, Manchester Science Park, Manchester Ml5 6SY, United Kingdom Intermediate Table Intermediate No. Name 1 4-Chloro-1_ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester 2 4 · Ethoxy-1H-pyrazolo[3,4-b]pyridine-5-carboxylate ethyl ester 3- 1-indolyl-4_ethoxy-1H-pyrazolo[3,4-b]pyridine · 5-Carboxylic acid ethyl ester 4 1_Yoyl-4_ethoxy-1Η_ρ than tons [3,4-b&quot; Kb lake-5-acid acid ethyl 5-methylchloro-1-phenyl- 1H-P is more than [3,4-b]p than bite-5-repulsive oxime. 6 1_Ethyl-4-amino hexahydroindole 7 1-methylindole-based hexahydropyridine 8 4-aminotetrachloromethane 8A tetrahydro-2H-pyran-4-amine hydrochloride = 4-aminotetrahydropyran hydrochloride 9 (R)-(+)-3-aminotetrahydro 4-Methyl 4-toluene hydrochloride 10 (S)-(-)-3-Aminotetrahydrofurfuryl 4-toluene hydrochloride 11 Tetrahydro-211_thiopipene-4-amine 12 Tetrahydro-3 - thiophene 87841-960303-中.doc -114- 1283678 13 Tetrahydro-3-sulfenylamine 1,i-dioxide hydrochloride 14 Tetrahydro-2H-thiopipene_4-amine_1,1_2 Oxide hydrochloride 15 4-chloro-based small ethyl Η Η-ρ than salido [3,4_b] pyridin-5-carboxylic acid 16 4-chloro-1-ethyl-1H-pyrazolo[3 ,4-b]pyridine_5_carbonyl chloride 17 N-benzyl-4-chloro-1-ethyl-1H·pyrazolo[3,4-b]pyridine-5-formamide 18 4-milk -1-ethyl-N-(2-ethylbutyl)_1H-p than spit[3,4-b]p than pent-5-carbamamine 19 4 _ chloroyl-1 ethyl-N -(4-fluorophenyl)·1Η·pyrazolo[3,4-b]pyridine-5-formamide 20 4-fluoro-N-cyclopentyl-1-ethyl-lH-p ratio [3,4-b]p ratio -5-5·carbamamine 21 4 _ chloro-1-ethyl _5_(tetrahydropyrrole_1-ylcarbonyl)-iH-pyrazolo[3,4-b&gt ; 比淀22 4-chloro-1(ethyl)-N-(pyridyl)methyl-pyrido[3,4-pyridin-5-carboxamide 23 4-chloro-based small ethyl propyl-1H-P is more than [3,4_b]p than yt-5-carbamide 24 4-chloro-1-ethyl-1H-P than [3,4-b]p -5-Mergamine 25 4-chloro-1-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester 26 4 ·Chloryl·1·decyl-1H· Pyrazolo[3,4-b]pyridine-5-carboxylate 27 4-Chloro-1-methyl-1H-pyrazolo[3,4-b]pyridine-5-carbonyl chloride 28 N-nodyl-4-yl-1-methyl-lH-p than wow And [3,4-b]bite-5-carbamamine 29 4_chloro-1-methyl-Ν·(4_fluorophenyl)_1H-pyrazolo[3,4_b]pyridine-5_ Formamide 30 4-Chloromethyl-methyl-(2-ethylbutyl)-1Η-pyrazolo[3,4_b]pyridine_5_carbamimidamide 31 4·Chloromethylmethyl-1H- Pyrazolo[3,4-b]pyridine-5-formamide 32 1-ethyl ice (tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-7] Pyridine-5-carboxylate ethyl ester 33 1-ethyl·4·(tetrahydro-2H-pyran-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxylic acid 34 1-ethyl chloro[(3S)_tetrahydrofuran-3-ylamino]-1H·pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester 87841-96〇3〇3·中. Doc -115- 1283678 35 1_Ethyl_4_[(3R)_tetrahydrofuran_3_ylamino]-1H-pyrazolo[3,4-7]pyridine-5-carboxylic acid ethyl ester 36 1·ethyl -4_(tetrahydro-2H-thiopyran-4-ylamino)-1Η-ρ ratio 并||3,4-b]pyridine-5-carboxylic acid ethyl ester 37 1-ethyl ice (four Hydrogen thiophene-3-ylamino)_iH_pyrazolo[3,4-b]pyridine·5-carboxylate ethyl ester 38 4-(cyclopropylamino)-1•ethyl-lH-p ratio [3,4 -b]p than 咱:-5-oleic acid ethyl ester 39 4-[(1,1-dihydrotetraphenylthio-3-yl)amino]-1-ethyl·1Η-pyrazolo[3, 4-b]pyridine-5-carboxylic acid ethyl ester 40 4-[(1,1-dihydrotetrahydro-2H-thiopiperidinyl)amino]-1-ethyl-1H-pyrazolo[ 3,4-b&gt;bipyridine_5_carboxylic acid ethyl 41 1-ethyl-4_[(3S)-tetrahydrofuran-3-ylamino]-1H-pyrazolo[3,4-bH pyridine-5 -carboxylic acid 42 ethyl 1-ethyl-4-[(3R)-tetrahydrofuran-3-ylamino]-1H-pyrazolo[3,4_b]external deuterium-5-acids 43 1-ethyl Ice (tetrahydro-2H-thiopiperazin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxylic acid 44 1-ethyl-4·(tetrahydrofuran -3-ylamino)-1Η-pyrazolo[3,4-b]pyridine·5-carboxylic acid 45 4-(cyclopropylamino)-1_ethyl-1H-pyrazolo[3,4- b]pyridine-5-carboxylic acid 46 4-[(1,1-dihydrotetramethylenesulfon-3-yl)amino]ethylethyl-1H-pyrazolo[3,4-b]pyridine_5 _Fusic acid 47 4-[(1,1-dihydrotetrahydro-2H-thiopiperan-4-yl)amino]]ethylethyl-1H-pyrazolo[3,4_b]pyridine-5-carboxylate Acid 48 4-(cyclohexylamine ratio also [3,4-b>pyramid-5-oleic acid ethyl ester 49 4-(cyclohexylamino)-1Η-pyrazolo[3+b]pyridine- 5-carboxylic acid 50 1-n-propyl -4-(tetrahydro-2H-piperazin-4-ylamino)_1H-pyrazolo[3,4-7] ton bite-5-rebel 51 4-milyl-1-ethyl·6_ Methyl-1H-P is more than [3,4-b]p than ethyl 5-carboxylate 52 4-(J-hexylamino)-1-ethyl-6-methyl-1Η-external b Sodium [3,4-b]r ratio _5-. carboxylic acid 87841-960303-中.doc-116- 1283678 53 1_ethyl-6-methyl-4-(tetrahydro-2H-pyran Ice-based amino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxylic acid 54 4-aminocyclohexanone hydrochloride intermediate 1 : 4-vapor-based small ethyl-1H-pyridyl Zymbly P,4-b]pyridine-5-carboxylate ethyl ester available from commercially available 5-amino-1-ethylpyrazole, as by G·Y et al. in «/· Μ / 2001 , 44, 1025-1027:

C02Et Intermediate 2: 4-Ethoxy-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester can be prepared by oxidative cleavage (Se02) of 1-furylmethyl derivative Cheng, as described by Τ·Μ·Bare et al., J. C/zem., 1989, 32, 2561-2573 (for further reference to Zuleski, F. R., Kirkland, KR, Melgar, M·D· Malbica, J. Drag, Metab. Dispos,, 1985? 13, 139)

tIntermediate 3· : ethyl 1-methyl-4-ethoxy-1H·pyrazolo[3,4-b]pyridine-5-carboxylate

C02Et a mixture of Intermediate 2 (0.47 g) and anhydrous potassium carbonate (0.83 g) (previously dried by heating at 10 ° C) in anhydrous dimethylformamide (DMF) (4 mL) Treat with methyl iodide (0.26 mL) and stir vigorously for 3 h. Then, the mixture was filtered through EtOAc-EtOAc (EtOAc) (EtOAc) 25 ml) for liquid separation. The layers were separated and the aqueous extracted with EtOAc EtOAc. The combined organic extracts were dried over anhydrous sodium sulfate and evaporated to an orange solid which was applied to &lt;RTIgt; The cartridges were successively eluted with EtOAc · • light oil (1:4, 1: 2, and 1:1), then chloroform:methanol (49:1, 19:1, and 9:1). The fractions containing the desired material were combined and concentrated in vacuo to give intermediate 3 (0.165 g). LCMS showed MH+ = 250; Tret = 2.59 min. —-Intermediate 4: ethyl 1-benzyl-4-ethoxy-1Η-pyrazolo[3,4-b]pyridine-5-carboxylate

Mixture of intermediate 2 (0.47 g) with anhydrous potassium carbonate (0.83 g) (previously dried by heating at 10 ° C) in dry DMF (4 ml) to benzyl bromide (72 g) ), then vigorously stirred and heated at mi for 4.5 hours. The mixture was allowed to cool, then filtered, and the filtrate was concentrated in vacuo to afforded oil, which was partitioned between DCM (25 mL) and water (25 mL). The layers were separated and the aqueous extracted with EtOAc EtOAc. The combined organic extracts were dried over anhydrous sodium sulfate and evaporated to a yellow oily solid, which was dissolved in DCM and applied to the SPE cartridge (20 g). The cartridge was eluted with EtOAc:light oil gradients (1:4, 1:2, and 1:1) then chloroform methanol (49:1, 19:1 and 9:1). The fractions containing the desired material were combined and concentrated in vacuo to give Intermediate 4 (······ LCMS showed 87841-% 〇3 〇3-med. doc -118-1283678 MH = 326; tret == 3.24 min. + smell 5_ : gas-based small phenyl_1H-pyrazolo[3,4_b]pyridine-5-carboxylic acid ethyl ester

a mixture of 5-amino-p-phenylpyrazole (2 g) and diethyl ethoxymethylenemalonate (2. 54 ml) under Dean Stark conditions at 120 ° C Heat for 16 hours. The falling liquid was allowed to cool, then cesium chloride (16 ml) was added, and the mixture was further heated under reflux for 20 hours. Excess phosphorus ruthenium chloride was removed in vacuo, and the residue was partitioned between diethyl ether and water. When water was added, it was carried out in a very strong manner. The ether-containing layer is washed with additional water, followed by dehydration drying with barium sulfate, and concentration in vacuo to give a chloro-phenyl small phenyl-1H-pyrazole [3,4] batch of _5-carboxylic acid. Ethyl ester (2. 〇 9 g). 〇:]\48 shows]\411+=302; Tret= 3.80 minutes. W-form 6: 1-Ethyl 4-_aminopyridinium I commercially available N1-aryl-4-amine hexahydro-p-precipitate, as by Yama (ja et al. in WO As stated in 00/42011:

Intermediate 7 : 1 -methyl 4 -aminohexahydropyridine is commercially available from N-methyl 4 -hexahydropyridone as obtained by CM. An (jersson et al. in WO 01/66521 Said: 87841_96〇3〇3·中.doc -119- 1283678

Intermediate 8: 4-Aminotetrahydropyranone available from Combi_Blocks, Inc., 7949 Silverton Avenue, Suite 915, San Diego, CA5 92126, USA (CAS 38041-19-9) H2N- Soils 8A: Tetrahydro-2H-piperazin-4-amine hydrochloride = 4_aminotetrahydropyranidine hydrochloride

Step 1: N^f-dibenzyltetrahydro-2H-piperidinamine Diamine (34.5 g) and acetic acid (6.7 ml) were added to tetrahydro-4H at 0 ° C to 5 ° C. Piper-4-one (16.4 g, commercially available, for example, from Aldrich) in a stirred solution of di-methane (260 mL). From 〇〇c to 5. After 2.5 hours of sputum, sodium triethoxysulfonate (38.9 g) was added in portions and the mixture was allowed to warm to room temperature. After stirring at room temperature overnight, the reaction mixture was washed successively with EtOAc EtOAc EtOAc (EtOAc (EtOAc) 45 grams). This oil was stirred with methanol (50 ml) at 4 ° C for 30 minutes to give a white solid (21.5 g). LCMS showed MH+ = 282; Tret = 1.98 min. Step 2 ····················································· And with hydrogenated 10% palladium/carbon catalyst (4 g), after 72 87841-96 〇 3 〇 3 · medium .doc -120 - 1283678 hours. The reaction mixture was filtered, and the filtrate was adjusted to pH 1 with 2M-hydrogen chloride in diethyl ether. The solvent was evaporated to give a crystal. In d6-DMSO, 27 ° C, 5 ppm) 8.24 (broad s, 3H), 3.86 (dd, 12, 4 Hz, 2H), 3.31 (dt, 2, 2 Hz, 2H), 3.20 (m, 1H), 1.84 (m, 2H), 1.55 (dq, 4, 12 Hz, 2H) · Intermediate 9: (R)-(+)-3-Aminotetrahydrofuran 4-tosylate is commercially available from FlukaChemie AG, Germany (CAS 111769-27-8)

Intermediate 10: (S)&lt;-)_3_Amino-Ammonia Bitter 4·Toluene-deposited acid can be obtained from Merck, Germany; or Ε· Merck (Merck), Hunter Boulevard, Magna Park , Lutterworth, Leicestershire, LEI7 4XN, United Kingdom (CAS 104530-80-5)

Intermediate 11: tetrahydro-2H-thiopiperan-4-amine is commercially available from tetrahydrothiopyran-4-one, as by Subramanian et al., /. Og. 1981, 46, Said in 4376-4383. The preparation of the hydrochloride salt can be achieved by conventional means.

Intermediate 12: tetrahydro-3_, phenoxyamine 87841-960303-中.doc -121 - 1283678 Prepared from commercially available tetrahydrodaphen-4-one in a manner similar to intermediate 11. The formation of the monthly deficit is described by Grigg et al., and the heart is called 1991, 47, 4477-4494, and the monthly reduction is described by Unterhalt et al., drc/z. 1990, 317-318.

Interstitial 13: Tetrahydro-3-pyrimidinamine 1,1-dioxide hydrochloride Commercially available from the Sigma Aldrich database of rare chemicals (CASLOR) (CAS-6338-70-1). The preparation of the amine hydrochloride can be achieved by conventional means.

_ Intermediate 14: tetrahydro-211-thiopipene 4-amine-1,1-dioxide hydrochloride in a similar manner to intermediate 11 from commercially available tetrahydropyrimidin . Oxidation to 1,1-di-S-synyltetraki-1 λ6-thiopyran-4-yl is described by Rule et al., J. Org. C/zem., 1995, 60, 1665-1673. . The 肟 formation system is described by Truce et al. in */· Og·C/zem·, 1957, 617, 620, and the reduction is described by Barkenbus et al., dm· &amp;c., 1955, 77, 3866. Subsequent preparation of the amine hydrochloride can be accomplished by conventional means.

Intermediate 15: 4-gasyl-1_ethyl·1Η·Bamboo I; attack and [3,4_b]p ratio bite_5·•rebel acid 87841-960303-中.doc -122- 1283678

N^Tl&quot;C〇2H

Et was treated with a solution of the intermediate in dimethylamine (28 ml) in the form of potassium hydroxide (6 g) in water (2 mL). Mixing (four) falls, J time", and then squeezing in a vacuum, acidifying to a positive 3 with a 2M aqueous solution of hydrochloric acid, and extracting with acetonitrile. The liquid layer is separated, and the organic layer is dried with sodium sulfate and then dried. Concentrated to give intermediate 15 as a white solid (2.4 g). LCMS: MH+ = 226; T ret = 2.62 min. s. 1H_pyrazolo[3,4-b]pyrazine-5-cartoamine

Intermediate 15 (3.5 g) was dehydrated and dried with phosphorus pentoxide for 1 hour and then treated with sulfinium dichloride (47 g). The mixture was stirred and heated at 75 ° C for 3 hours. Excess ruthenium dichloride was removed in vacuo, and the residual oil was azeotroped with dimethyl ketone (DCM) to give intermediate 16 which was assumed to be a gasified hydrazine derivative of intermediate 15 in white. Solid (3.3 g). Intermediate 16 (0.473 g) was dissolved in THF (4 mL) EtOAc (EtOAc) The mixture was stirred under nitrogen for 0.5 hours. The mixture was concentrated in vacuo 87841-960303-M. doc-123-1283678 and then partitioned between dichloromethane and water. The layers were separated and the organic material was concentrated in vacuo to afford Intermediate 17 (0.574 g). LCMS showed MH+ = 315; Tret = 2.90 min. The following materials were prepared in a similar manner:

NR4R5 Amine Reagent MH+ Ion TreiT (min) Intermediate 18 2-Ethylbutylamine 309 3.07 Intermediate 19 4-Fluoroaniline 319 3.08 Intermediate 20 Wide NH Cyclopentylamine 293 2.76 Intermediate 21 Tetrahydropyrrole 279 2.46 Intermediate 22: 4_gas- 1 -ethyl (pyridin-4-ylmethyl)·1Η-pyrazolo[3,4-b]pyridine-5-carboxamide

The ruthenium chloride intermediate 16 is synthesized from the intermediate 15 using the method shown above for the intermediate π. Intermediate 16 (0.473 g) was dissolved in THF (4 mL) eluted with diisopropylethylamine (DIPEA) (0.509 mL) and then 4-(amino thiol) b-pyridine (0.211 g) Treated and the mixture was stirred under nitrogen for 5 hours. The mixture was concentrated in vacuo and then partitioned between DCM and water. The layers were separated and the organic material was concentrated in vacuo and then applied to a EtOAc EtOAc EtOAc (EtOAc) 3_中.doc -124-1283678 to 〇: 1), followed by dissolution with MeOH: EtOAc (5: 95, then 10: 90). The fractions containing the desired material were combined and concentrated in vacuo to give intermediate 22 (0.086 g). LCMS showed MH+ = 316; Tret = 1.84 min. Interstitial 23 · 4-Alkyl_1_ethyl-N-n-propyl-1H_p is more than [3,4-b]pyrene~-5-methylamine

The ruthenium chloride intermediate 16 is synthesized from the intermediate 15 using the method described above for the intermediate 17. Intermediate 16 (0.473 g) was dissolved in THF (4 mL) EtOAc (EtOAc) Then another portion of n-propylamine (0.023 g) was added and stirring was continued for 18 hours. The mixture was concentrated in vacuo and then partitioned between DCM and water. The layers were separated and the organic material was concentrated in vacuo to afford Intermediate 23 (0.405 g). LCMS showed MH+ = 267; TRET = 2.54 min. Intermediate 24: 4-Alkyl·1·Ethyl-1H-pyrazolo[3,4_b]pyridine_5-carboxamide

The ruthenium chloride intermediate 16 is synthesized from the intermediate 15 using the method described above for the intermediate 17. Intermediate 16 (0.30 g) was dissolved in THF (3 mL) and EtOAc (EtOAc) The mixture was stirred under nitrogen for 18 hours. Add another portion of hydrazine in the dioxane to 5 Μ ammonia (4.92 mM 87841-96 〇 3 〇 3-中 .doc -125-1283678 liters) and continue to stir for 72 hours. The mixture was concentrated in vacuo and the residue was partitioned between DCM and 2M sodium hydroxide. The layers were separated and the organic material was concentrated to give intermediate 24 (0.278 g). LCMS showed MH - 225 &gt; Tr e τ = 2.10 minutes. Earth··Interstitial 25 : 4-methyl-l-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester

Mixture of 5-amino-1-methylpyrazole (4. gram) with diethyl ethoxymethylenemalonate (9.16 liters) at i5 ° C under Dean Stark conditions Heat for 5 hours. Phosphine chloride (55 ml) was carefully added to the mixture, and the resulting solution was at 130. (: and heating under reflux for 18 hours. The mixture was concentrated in vacuo, then the residue was evaporated in EtOAc EtOAc EtOAc (EtOAc) And the combined organic extracts were dried over anhydrous sodium sulfate and concentrated in vacuo. The residual solid was purified by Biotage chromatography (gels, 90 g) eluting with EbO: light oil (1:3) The fractions containing the desired material were combined and concentrated in vacuo to give Intermediate 25 (················ 〃比攻和[3,4-b]P than bite-5-rebel

A solution of the intermediate 25 (4.0 g) in dioxane (3 mL) was used as a solution in water (20 mL) with a solution of 78,418-960, 303 - doc - 126 - 1283 678 (7.54 g). deal with. The mixture was stirred for 16 hours, then diluted with water (150 mL) and acidified to pH 3 with 5M aqueous hydrochloric acid. The mixture was stirred in an ice-bath for 15 min then EtOAc (EtOAc)EtOAc. LCMS showed MH+ = 212; Tret = 2.26 min. _also a substance 28 ··································

The intermediate 26 (2.5 g) (dehydrated in advance with phosphorus pentoxide) was treated with sulfinium dichloride (25 ml), and the mixture was heated under reflux for 1 hour. Excess ruthenium dichloride was removed in vacuo to give intermediate 27 as a gasified hydrazine derivative of intermediate 26 as a white solid (27 g). Intermediate 27 (0.68 g) was dissolved in THF (10 mL) eluting with EtOAc (EtOAc) The mixture was concentrated in vacuo and then partitioned between dcm (20 mL) and water (10 mL). The liquid layer was separated and the organic material was concentrated in vacuo to afford Intermediate 28 (0.90 g). LCMS showed MH+ = 301; Tret = 2.72 min. The following materials were prepared in a similar manner: 87841-960303-中.doc -127- 1283678

Nr4r5 amine reagent MH+ ion Tret (minutes) intermediate 29 4-fluoroaniline 305 2.91 intermediate 30 hn^j^ 2-ethylbutylamine 295 2.97 ί__interstitial 31 : 4-chloro-1 -methyl 1Η_峨bit and [3,4-b]峨 violation_5-甲甲胺

'Γ ^ Me νη2 ruthenium chloride intermediate 27 was synthesized from the intermediate 26 using the method shown above for the intermediate 28. Intermediate 27 (0.68 g) was then treated with a 0.5 M solution (17.7 mL) of ammonia in dioxane. Then diisopropylethylamine (0 51 ml) was added and the mixture was stirred for 21 hours. Then, the mixture was subjected to liquid separation between DCM (100 ml) and water (30 ml). The insoluble solid was removed by filtration, washed with water (20 mL) and dried with EtOAc EtOAc EtOAc LCMS showed MH+ = 211; Tret = 1.84 min. Soil 32 (=Example 3): 1-ethylidene (tetrahydro-2H-piperidinylamino)-1Η-pyrazole and [3,4-b]pyridine-5-carboxylic acid ethyl ester

C〇2Et

87841-960303-ψ.άοο 128- 1283678 Intermediate 1 (0·20 g) and triethylamine (0.55 ml) were suspended in ethanol (8 ml) and 4-aminotetrahydropyran (0.088 g) was added. ). The mixture was heated with stirring under nitrogen at 8 ° C for 16 hours and then concentrated in vacuo. The residue was subjected to liquid separation between DCM and water. The liquid layer was separated and the organic layer was directly loaded onto an SPE cartridge (5 g), which was successively used; (i) DCM, (ii) DCM: Et20 (2: 1), (iii) DCM: Et20 (l: l), (iv) Et20 and (v) EtOAc were dissolved. The fractions containing the desired material were combined and concentrated in vacuo to afford Intermediate 32 (0.21 g). 1^]^ shows the leg += 319; 1 ^ Ding = 2.93 minutes. Soil 33: 1_ethyl-4-(tetrahydro-2H- sher-4-ylamino)pyrazine[3,4-b]pyridine-5-carboxylic acid

The solution of Intermediate 32 (0.21 g) in ethanol: water (95: 5, 10 mL) was treated with nitrogen emulsified steel (0.12 g). The mixture was taken at 5 Torr. Heated under the arm for 8 hours, then concentrated in vacuo, dissolved in water, and acidified to pH 4 with EtOAc. The white solid which formed was removed by filtration and dried under vacuo to give intermediate material 33 as pale white solid (0.156 g). LCMS showed MH+ = 291; Tret = 2.11 min. Soil. 34 (=.1.): 1_Ethyl-4_[(38)_tetrahydrofuran-3-ylamino]-1H-pyrazolo[3,4_b]pyridine-5-carboxylic acid Ethyl ester 87841_960303·中.doc -129- 1283678

NHRJ

C〇2Et Intermediate 34 NHR3= HN.n..&lt;Qj. Intermediate 1 (0.05 g) and (S)_(I)_3_Aminotetrahydrofuran oxime sulfonate (0.052 g) were suspended in ethanol (1 ml) Medium and add triethylamine (〇 14 ml). The mixture was stirred under nitrogen and heated at 8 (rc) for 24 hours. After cooling to room temperature, 4 was removed by evaporation under a stream of nitrogen, and the residue was taken from (2 mL) and water (1. The mixture was separated and the layers were separated and the organic layer was concentrated to dryness. Purified using EtOAc EtOAc: EtOAc (EtOAc) : 4i: 21: 1 and 1: 〇) Dissolution. The fractions containing the desired material were combined and concentrated in vacuo to give EtOAc (EtOAc: EtOAc) The following materials were prepared in the same manner: NHR3

Amine reagent MH+ ion Tr ET (minute, intermediate 35 ί=Example 9) /NH —----- (R)-(+&gt;3_Aminotetrahydrofuran 4-methyl sulfonate 305 JIX JCi X ' ^SEm / 2.73 Intermediate 36 0 = Example 10) ηνΌ Intermediate 11 335 3.21 Intermediate 37 (=Example 11) 中间 Intermediate 12 321 3.10 87841-960303-中.doc -130- 1283678 Intermediate 38 (=Meetings 12) long NH cyclopropylamine 275 2.98 _ intermediate 39 (= Ui 13) ··· 4_[(1,[tetrahydropyrimidin-3-yl)diamine]ethylethyl-1H-pyrazole [3,4-b]pyridine-5-carboxylic acid ethyl ester

Intermediate 1 (5 g of 〇·〇) and intermediate 13 (0.027 g) were suspended in ethanol (1 ml) and triethylamine (0.14 ml) was added. The mixture was stirred under nitrogen and heated at 80 ° C for 24 hours. After cooling to room temperature, the ethanol was removed by evaporation under a stream of nitrogen, and the residue was partitioned between DCM (2 mL) and water (1·5 mL). The layers were separated and the organic layer was concentrated to dryness. Purification was carried out using a SPE cartridge (silica gel, 5 g) eluting with a gradient of EtOAc: hexanes (1:8, then 1:4, 1:2, 1:1 and 1: s). The fractions containing the desired material were combined and concentrated in vacuo to give intermediate 39 (= </ RTI> <RTIgt; LCMS showed MH+ = 3 纟 3; TRET = 2.60 min. The following materials were prepared in a similar manner: NHR3

C〇2Et NHR3 Amine reagent MH+ ion Tr^et (minutes) Intermediate 40 (=Example 14, Intermediate 14 367 2.64 ί·Interstitial 41: 1-Ethyl-4-[(3S)_Tetrahydrocyanate· 3_ylamino]-111_pyrido[3,4-b] 87841_96〇3〇3_中.doc -131- 1283678 pyridine-5-carboxylic acid NHR3

n^yVc〇2H Intermediate 41 NHR3= HN...·· The solution of the intermediate 34 (0.037 g) in r _ , the skill brother in Ethyl • Water (95: 5, 33⁄4 liter), gas Oxidation of sodium (0_019 g). The mixture was heated under a heat for 16 hours: :, concentrated in True 2. The residue was dissolved in water (1 mL) and acidified to pH. The formed white solid sink was removed by filtration and dried under vacuum. The filtrate was extracted with ethyl acetate and the organic layer was collected and concentrated in EtOAc to give a white solid. The two solids were combined to give intermediate 41 (0.033 g). LCMS showed MH+ = 277; Tret = 2.05 min. The following materials were prepared in a similar manner:

NHR3 Starting material MH+ ion Tret (minutes) Intermediate 42 /NH Intermediate 35 277 2.05 Intermediate 43 HN-~~( &gt; Intermediate 36 307 2.40 Intermediate 44 /NH Intermediate 37 293 2.59 Intermediate 45 Long NH Intermediate 38 247 2.24 Intermediate HN. Intermediate 39 325 2.05 87841-960303·中.doc -132- 1283678 _46 Intermediate __47 Intermediate 40 339 2.05 : 4_(cyclohexylamino)_1H-pyrazolo[3 , 4_b]P than pyridine_s_carboxylic acid ethyl ester

C02Et 中间 Intermediate 2 (0-69 g) was suspended in cyclohexylamine (ι·〇ι ml), and the mixture was heated at 90 ° C for 3 hours. The residual mixture was cooled to room temperature and partitioned between chloroform (25 mL) and water (25 mL). The liquid phase is separated and the organic phase is evaporated to dryness. The residue was triturated with EtOAc (25 mL). LCMS showed tf ΜΗ+ = 289, Tr ε τ = 2.91 min. Interstitial 49 : 4_(cyclohexylamino)_1H_pyrido[3,4_b]pyridine-5-rebel

Η co2h 2 Μ-NaOH solution (〇·5 ml) was added to a stirred suspension of intermediate 48 (0.2 g) in dioxane (4 mL) and water (5 mL). After the overnight fall at room temperature, the reaction mixture was heated at 4 ° C for 8 hours. Another amount of 2M-sodium hydroxide solution (15 ml) was added, and the reaction mixture was heated at 40 87841-960303···doc -133 - 1283678 °C for 48 hours. The reaction solution was concentrated, diluted with water (10 mL), and evaporated. The precipitate formed was collected by filtration, washed with water, and dried to give Intermediate 49 (0.18 g). LCMS showed MH+ = 261;

Tret = 2.09 minutes. Intermediate 50 ·· 1_正-propyl-4-(四风-2H_叫喃_4_ylamino)_1H-p ratio 峻[3,4· b]pyridine-5-carboxylic acid

A 2 M solution of sodium hydroxide (0.7 mL) was added to a stirred suspension of EtOAc (5. <RTI ID=0.0></RTI> </RTI> <RTIgt; After stirring at room temperature overnight, another amount of 2 Μ-sodium hydroxide solution (〇·7 mL) was added, and the reaction mixture was heated at 43 ° C for 2.5 hours. The reaction solution was concentrated, diluted with water (5 mL) The precipitate formed by filtration was collected, washed with water, and dried to give Intermediate 50 as a white solid (14 g). LCMS showed MH+ = 305; T rt = 2.42 min. Intermediate ϋ : ‘Alkyl-1-ethyl_6-methyl-1Η-pyrazolo[3,4-b]pyridine-5-carboxylic acid Ethyl ester 87841-960303-中.doc -134- 1283678

5-Amino-1-ethyl p ratio (1.614 g, 14.5 mmol) with diethyl 2-(1-ethoxyethylidene)malonate (3.68 g, 16·〇 A mixture of millimolars, as described by PPT Sah5 /. Amen Ckm. 1931, fl, 1836, was heated at 150 C under Dean Stark conditions for 5 hours. Chlorinated scale (25 ml) was carefully added to the mixture, and the resulting solution was heated at 130 ° C for 18 hours under reflux. The mixture was concentrated in vacuo and the residual oil was carefully added to water (100 mL) and cooled. The resulting mixture was extracted with EtOAc (EtOAc)EtOAc. The residual oil was purified by Biotage chromatography (silica gel, 90 g) and dissolved in ethyl acetate-light oil (1: 19). The fractions containing the desired product were combined and concentrated in vacuo to afford Intermediate <RTI ID=0.0> Lcms shows MH+ = 268; Tret = 3.18 minutes. +Interstance 52 : 4-(cyclohexylamino)ethylidene-6-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid

Example 190 (0.128 g, 〇·39 mmol, described later) in 87841-960303-中.doc-135- 1283678 ml), and the mixture was heated at 50 ° C for 16 hours. The reaction mixture was concentrated, and the resulting aqueous solution was neutralized with a 2M salt plate to precipitate a solid which was collected by filtration. The filtrate was applied to an OASIS® hydrophilic _ lipophilic balance (hlb value) extraction cartridge* (1 gram) which was dissolved in water followed by methanol. Evaporation of the MeOH afforded a solid which was combined with the solid that was initially precipitated to afford Intermediate 52 (0.083 g) as a white solid as a carboxylic acid. * OASIS® HLB extraction cartridges are available from Waters, 34 MapleS, Milford, MA01757, USA. The cartridge comprises a column containing a copolymer sorbent having an HLB value such that when the aqueous solution is dissolved through the column, the solute is absorbed or adsorbed into or onto the sorbent and causes dissolution of the organic/table In the case of a reagent such as methanol, the solute is released as an organic (e.g., methanol) solution. This is a method of separating solute from aqueous solvent. History $ # 53 : 1-ethyl fluorenyl ice (tetrahydro-2-indole-piperidin-4-ylamino)-1Η-pyrazole and [3,4-b]pyridine-5carboxylic acid

2M-sodium hydroxide solution (0.75 ml, 1.5 mmol) was added to 189 (0.248 g, 0.75 mmol, as described below) in ethanol (2 mL) and the mixture was heated under reflux. 16 hours. The reaction mixture was concentrated, diluted with water (1 mL), and then acidified with 2M-hydrochloric acid (0.75 ml) to allow the solid to be dissolved, 87841-960303-medium doc-136-1283678. Matter 53 (0·168 g). LCMS showed MH+ = 305; Tret = 1.86 min. Intermediate 54 : 4-Aminocyclohexanone hydrochloride

NH..HCI A solution of hydrogen chloride in dioxane (0.5 ml, 2.0 mmol, 4 M) was added to the 4-keto-cyclohexylaminocarbamic acid tert-butyl ester (0.043 g, 0.20 mmol). It is commercially available from Astatech, Philadelphia, USA in a stirred solution of dioxane (0.5 ml) and the mixture is stirred at room temperature. After 1 hour, the reaction mixture was evaporated to give a m. 1H NMR (400MHz in d6-DMSO, 27°C, 5 ppm) 8.09 (broad s, 3H), 3.51 (tt, 11, 3.5Hz, 1H), 2.45 (m, 2H, partially masked), 2_29 ( m, 2H), 2.16 (m, 2H), 1.76 (m, 2H). Intermediate 54A: N-benzyl-4-(cyclohexylamino)-1 Η-pyrazolo[3,4-b]pyridine -5-formamide

The decylamine (0.16 mL) was added to a stirred mixture of intermediate 49 (0-13 g), DIPEA (0.26 mL) and HATU (0-285 g) in DMF (3 mL). The mixture formed by 87841-960303-中.doc -137-1283678 was cooked and removed at 85 ° C for 16 hours. Another portion of HATU (〇.H), DIPEA (0.13 mL), and benzylamine (0.082 mL) were added and the mixture was heated at 88 °C for 16 hours. The resulting solution was concentrated, diluted with methylene chloride (EtOAc) (EtOAc) The residue was purified on a spE cartridge (eluent, 20 g) eluting with 60-80% ethyl acetate in cyclohexane. The residue was further purified on an SPE cartridge (Isolute SCX acid cartridge, 5 g χ2), dissolved in methanol (2 x 20 mL) and 10% ammonia (4 x 20 mL) in methanol; Concentrate to give the intermediate as a white solid (0.07 g). LCMS showed MH+ = 350; Tret = 2.99 min. Intermediate 55 : 4_ gas-based small ethyl-N-{[4_(methoxy)phenyl]methyl iH_pyrazolo[3,4-b] bamboo li bite-5-cartoamine

Intermediate 15 (1.04 g) was treated with sulfuric acid dichloride (13.22 g). The mixture was stirred and heated at 75 C for 2 hours. Excess ruthenium dichloride was removed in vacuo and the residual oil was azeotroped with toluene to give intermediate 16 which was taken to be a yttrium chloride derivative of intermediate 15 as a creamy solid (112 g). Intermediate 16 (0.997 g) was dissolved in tetrahydrofuran (THF) (25 mL) eluted with N,N-diisopropylethylamine (1.07 ml), then ι_[4-(methoxy)phenyl] Methylamine 4-methoxybenzylamine (〇·54 ml) (available, for example, from Aldrich, Acros or 87841-960303-φ. (1οο -138-1283678)

Lett, 20025 43 (48), 8735; or Meindl et al, J; M by /· C~m·, 1984, 27 (9), 1111; or Leiters, 2002, 4 (12), 2055), and Stir the mixture: mix for 3 hours. The solution was concentrated in vacuo and then separated between DCM and water. The layers were separated and the organic material was concentrated in vacuo. Next, the solid was triturated in 1:1 ethyl acetate: cyclohexane to give Intermediate 55 ( 1.27 g). LCMS showed MH+=345 and Tret = 2.86 minutes. The following materials were prepared in a similar manner:

Source of nr4r5 HNR4R5 MH+ ion Tret (minutes) Intermediate 56 [J Λ· Lis et al., J. Med·Chem" 1990, 33 (10), 2883, see Figure III and reference 24 408 2.60 Intermediate 57 nh ~C〇Maybridge-Int ; or Aldrich ; or TCI-America 341 3.08 Intermediate 58 : 1-ethyl-4-[(4-ketocyclohexyl)amino]-1Η-pyrazolo[3,4- b]pyridine-5-carboxylic acid

87841-960303-中.doc -139- 1283678 A solution of sodium hydroxide (0.053 g ' 1.32 mmol) in water (〇 41 ml) was added to Example 205 ((U g, 〇.303 mmol) The resulting mixture was heated in 5 (TC) in EtOAc (1 mL). EtOAc (2 EtOAc) The combined organic extracts were dehydrated (Na^O4) and evaporated to give Intermediate <RTI ID=0.0>#</RTI> </RTI> <RTI ID=0.0></RTI> <RTIgt; Intermediate 58A: ethyl 1-ethyl- 4-(tetrahydro-2 Εμ trace _3_ ylamino)-1 Η-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester

Intermediate 1 (0-76 g, 3.0 mmol) was dissolved in acetonitrile (1 mL). Add tetrahydro-2H-piperidin-3-amine hydrochloride (〇·5 g, 3.6 mmol, eg. as 1988, 84, 148) with N,N-diisopropylethylamine (3.14 Love) Liter, 18.0 mmol, and the mixture was stirred at 85 ° C for 24 hours. After 24 hours, another portion of tetrahydro-2H-piperidin-3-amine hydrochloride (0.14 g, 1.02 mmol) was then weighed and continued at 85 〇c. After a further 8 hours, the mixture was concentrated in vacuo. The residue was partitioned between DCM (20 mL) and water (12 mL). The layers were separated and the aqueous extracted with EtOAc EtOAc. The combined organic extracts were dried (Naj.sub.4) and concentrated in vacuo to afford a brown solid which was purified on EtOAc EtOAc EtOAc 16, 1 : 8, 1 : 4, 1 : 2, 1 : 1,1 : 0) Dissolution. The 87841-960303-medium doc-140-1283678-soluble fractions containing the desired material were combined and evaporated to give intermediate 58 (yield: 89 g). Lcms shows MH+=319; Tret = 2.92 minutes. Intermediate _: Buethyl ice (tetrahydropyridinylamino)_1H_pyrazolo[3,4_b]

A solution of the intermediate 58A (0.89 g, 2.79 mmol) in ethanol (16.7 mL) was then taken up in sodium hydroxide (0.47 g, 11.7 mmol) in water (31 liters). The mixture was stirred at 50 °C. After 12 hours, the reaction mixture was evaporated EtOAc mjjjjjjjjj At 0. (After stirring for 30 minutes, the formed precipitate was collected by filtration, washed with EtOAc EtOAc (EtOAc) 291 ; Tret = 2.19 min. Intermediate 60 : 4-[(1-Ethyl-4_hexahydropyridyl)amino]-1-ethyl-1H-pyrazolo[3,4_b] -5-acid

-141- 87841-960303-中.doc 1283678 Aqueous sodium hydroxide (8.55 mL, 2M) was added to a solution of 207 (l. The mixture was taken at 5 Torr. Heating under the arm for 18 hours' then neutralized with aqueous hydrochloric acid and evaporating in vacuo to give 丨-ethyl-4-(4-hexahydropyridylamino)-1 Η-pyrazole [3,4_b> ratio Mixture of pyridine-5-carboxylic acid with 4-[(1-ethylindolyl-4_hydrogen p-pyryl)amino]diethyl-pyrolo[3,4_b]u ratio biting_5-carboxylic acid . Add acetic acid (0. 36 ml) to a mixture of HATU (2.41 g) and N,N-diisopropylethylamine (2.21 ml) in N,N-dimethylformamide (65 ml) Inside. After stirring for 15 minutes, the mixture was added to μethyl (4-6 hexa-p-decylamino)-indole-pyrazolo[3,4-b]pyridine-5-carboxylic acid and 4-[(1- To a mixture of ethionyl-4-hexahydropyridyl)amino]-1-ethyl-1H.pyrazolo[3,4hepta]pyridine-5-carboxylic acid, the reaction was stirred for 15 h. The reaction mixture was evaporated in vacuo <mjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjj White solid. LCMS showed MH+ 334; Tret = 2.06 min. Soil 61.6 (cyclohexylamino) small ethyl_1H·^ ratio also [3,4_b]v than lake-5-carboxylic acid

A solution of Example 2 (5.37 g of '17 Torr) in ethanol (3 mL) was treated with a solution of air-emulsified steel (2.72 g '68 mmol) in water (2 mL), 87841- 960303-Medium_doc-142- 1283678 The resulting mixture was stirred at 50 ° C for 3 hours. The reaction mixture was concentrated in vacuo to dissolve in water (250 liters) and the cooled solution was acidified to pH 1 with 5M hydrochloric acid. The solid which formed was collected by filtration and dried in vacuo to give Intermediate <RTIgt; LCMS showed MH+ = 289; Tr e τ = 2.83 min. Soil material: 1,1-dimethylethyl (4,4-difluorocyclohexyl)carbamate

Adding (diethylamino)sulfur trifluoride (DAST) (〇.〇6 ml, 〇·47 mmol) to (4-酉-ylcyclohexyl)urethane, ι,ΐ-dimethyl The ester (25 mg, U7 mmol, commercially available from AstaTech, Philadelphia, USA) in a stirred solution of anhydrous gas (5 mL) in nitrogen and 2 Torr. Stir the mixture under the arm. After 22 hours, the reaction mixture was cooled to EtOAc EtOAc (EtOAc) The liquid phase was separated by a water-repellent glass and the aqueous phase was extracted with DCM (5 mL). The combined organics were concentrated in vacuo to give EtOAc (EtOAc: EtOAc). 140 mg), containing 1,1,1-dimethylethyl (4. fluoro-3-cyclohexen-1-yl)carbamate. iHNMR (400MHz, in CDC13, 27 C, 5 ppm) less components: δ 5.11 (dm, 16 Hz, lH), 4.56 (br, lH), 3.80 (br, lH) 2.45-1.45 (m's, 6H excess) , l.43(s, 9H). Main components: 87841-960303-中, doc -143 - 1283678 54.43 (br,1H),3·58 (br,1H),2.45-1.45 (m,s,8H excess ), 1.45(s,9H)· Intermediary 63 : (4,4-difluorocyclohexyl)amine hydrochloride

A solution of hydrogen sulfide in dioxane (4M, 1.6 ml) was added to intermediate 62 (140 mg, 0.6 mmol) in dioxane (1·6 mL) at 20 °C. It is stirred in the solution. After 3 hours, the reaction mixture was concentrated in vacuo to give titled <RTI ID=0.0></RTI> <RTIgt;

1H NMR (400 MHz in dg-DMSO, 27 °C, 5 ppm) less components: 8.22 (br, 3H excess), 5.18 (dm, 16 Hz, lH), 3.28-3.13 (m, lH excess), 2.41_ 1·53 (m's, 6H excess) · Main components: 58.22 (br, 3H excess), 3.28-3.13 (m, 1H excess), 2.41-1.53 (mfs, 8H excess) · Impurities are also present. Soil · Interstitial 64 · 4-gas-1-ethylmethyl-1H·〃比峻和[3,4-b] 外b bit_5_甲甲胺

Intermediate 15 (0.06 g, 0.266 mmol) was treated with sulfinium dichloride (〇·48 mL). The mixture was disturbed and heated at 75 ° C for 2 hours. Excess ruthenium dichloride was removed in vacuo and the residual oil was azeotroped with dichloromethane (DCM) to afford intermediate 16 which was assumed to be the ruthenium chloride derivative of intermediate 15 as a white solid. Intermediate 16 was dissolved in dry tetrahydrofuran (th) (2 mL) and taken to N,N-diisopropylethylamine (DIPEA) (0.069 mL) then methylamine (2M in tetrahydrofuran) , 〇·ΐ 5 ml) was treated, and the mixture was stirred under a nitrogen atmosphere of 87481-960303-media.doc • 144·1283678 for 16 hours. An additional 〇 5 ml of methylamine (2M in ΤΗρ) was added and the solution was stirred for 2 hours. The mixture was concentrated in vacuo then EtOAc (2 mL) EtOAc. The layers were separated and the organic material was concentrated in vacuo to afford Intermediates <RTIgt; LCMS showed MH+ = 239; Tret = 2.17 min. Interstitial 65_: called (1) (10) upper dimethylethyl)oxy] condensyl}_4_hexahydropyridyl)amino]_1_ethyl_1H-pyrazolo[3,4-b]acridine-5 _carboxylic acid ethyl ester

Intermediate 17 (2.0 g, 6-37 mmol), 1,1-dimethylethyl 4-aminopyridinium carboxylate (2.04 g, 10.2 mmol) and N,N-diisopropyl A mixture of ethylamine (5.54 mL, 3 L 9 mmol) in MeCN (40 mL). The reaction was evaporated and the residue was partitioned between DCM and water. The organic phase was dried (MgS04) and then evaporated in vacuo. The residue was chromatographed on EtOAc (EtOAc) (EtOAc) LCMS showed MH+ = 479; Tret = 3.37 min. _ Intermediate 67: 3-Amino-N-cyclohexyl-N-methylbenzamide

87841·96〇3〇3·中.doc -145- 1283678 '3-Chloronitrobenzoquinone (2 g, 1〇78 mmol) in DCM (20 ml) at 20 °C The solution was added dropwise to N_methylcyclohexylamine (10 ml, 14.01 mmol), n,N-diisopropylethylamine (3/76 mil) and N,N-dimethylaminopyridine. (〇·〇ι克) The rise in dcm, 21.56 mmol was stirred in the mixture. The reaction mixture was stirred for 56 hours and then evaporated in vacuo. The residue was subjected to liquid separation between ethyl acetate and water. The organic phase was washed with a Ηα aqueous solution, followed by dehydration drying (MgS 〇 4), and evaporation in vacuo. The residue was purified by chromatography on silica gel to give N-cyclohexyl-N-methyl-3-nitrobenzoate as cyclohexane:Et〇Ac (9: 丨, then 2 ·· ^ falling off ' Indoleamine (14 g). MS shows ΜΗ+=263· Ν-cyclohexyl-Ν·methyl-3-nitrobenzamide (Ig 4 g, 5.35 mmol) and I A mixture of bar/carbon (5%, 0.140 g) in EtOAc (EtOAc) (EtOAc) (0.107 g) LCMS showed MH+ = 233; TRET = 2.56 min. Intermediate 68: N-ethyl- 4- keto-1-hexahydropyridinamide

a solution of ethyl isocyanate (2·31 g, 32.5 mmol) in DCM (40 mL) was added dropwise to 4-hexahydromethanol in 15 min. Monohydrate hydrochloride (5.0 g, 32.5 mmol, commercially available from Aldrich) and carbonic acid 87481-960303-ψ.άοο -146- 1283678 sodium hydride (8.2 g, 97·5 mmol) in water (6 〇 ml) in a vigorously stirred solution. The reaction mixture was stirred at room temperature for 20 hours. Sodium chloride (7 g) was added to the reaction mixture, and the organic phase was separated. The aqueous phase was extracted with a further Dcm (3 X 75 mL). The combined organic extracts were dried (MgSO4) and evaporated in vacuo to give a white solid. Recrystallization from ethyl acetate: cyclohexane k (10 · 1) afforded Intermediate 68 as a white solid (2 J). TLC (silicone) obtained Rf = 〇.24 (ethyl acetate) · Analytical value: c, 56.7; H, 8.3, N, 16.35. C8H14N2 〇 2 requires c, 56.5; Η, 8·3; N, 16.5. Soil 69 · 4-Amino-Ν·Ethyl-1-hexahydroindole A ugly amine νη2 ό Λ, intermediate 68 (u gram, 8.8 mmol) with guanamine (1 〇 4 g, 9 7 mmoles of a solution in absolute ethanol (60 liters) on a pre-reduced 1% palladium on carbon catalyst (0.6 g) in hydrogen (2 mL) until hydrogen absorption has ceased So far (22 hours). The reaction mixture was passed through a filter (diatomaceous earth), and then filtered through a silica gel (100 liters), and dissolved in ethanol: 〇 88 ammonia _ : 丨) to obtain a black oil. The oil was dissolved in ethanol (30 ml) and treated with a solution of hydrogen chloride in ethanol (3M) until the solution was acidic. The solvent was evaporated and the residue was crystallised from ethanol to give intermediate 69 as a white solid. (1〇9g). TLc (矽胶)' obtained Rf = 0.73 (ethyl acetate: decyl alcohol, 1 〇: 1}. Analytical values: C, 45.9, H'8.4' N, 19.8. C8 printed 8ClN3 〇 requires Q 46.3; H, 8.7 N,20.2. 87841-96〇3〇3·中.doc •147- 1283678 Intermediate: ({4-[(Cyclopropylamino)-based]phenyl}methyl)carbamic acid 14-dimethyl Ethyl ester

Add cyclopropylamine (0.136 g, 2.39 mmol) to diisopropylethylamine (〇68 mL '3.9 mmol) to 4·[({[(1,1_dimethyl) Alkyloxy]carbonyl}amino)methyl]benzoic acid (0.501 g, 2.0 mmol), EDC (0.612 g, 3.2 mmol) and hydrazine (0.35 g, 2.6 mmol) in DMF (2) In a stirred solution in milliliters). The resulting mixture was stirred at room temperature overnight. The solvent was removed in vacuo and the residue was crystalljjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjj The organic phase is dehydrated and dried, and evaporated in vacuo to give a crude product which is purified by Biotage chromatography (separation) and eluted with ethyl acetate: cyclohexane (1.3:1) to give an intermediate. As a white solid (0.512 g). LCMS showed MH+ = 291; Tret = 2.75 min. Soil-intermediate 71 : 4_(Aminomethyl)cyclopropylbenzamide

A

• HCI Under nitrogen, intermediate 70 (0.506 g, 1 J4 mmol) was dissolved in a solution of chlorinated children in dioxane (20 mL, 4 M). After 1 hour, methanol (ml) was added to the mixture and stirring was continued at room temperature overnight. The solvent was removed in hexane to give Intermediate 71 as a white solid ( 416 g) </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; Intermediate 72

Intermediate 33 (1.36 g, 4.7 mmol), EDC (1. 26 g, 6.57 mmol) and hydrazine (0.76 g, 5.62 mmol) were suspended in DMF (5 mL). Stir vigorously at room temperature for 0.5 hours, then add 1,1-dimethylethyl 4-(aminomethyl)hexahydropyranoate (1.3 g, 6.07 mmol, commercially available from Maybridge Chemical company). After stirring at room temperature overnight, another quantity of car (aminomethyl)-ι-hexahydropyridinecarboxylic acid u-dimethylethyl ester (1 〇 1 g, 4.7 mmol) was added to The reaction mixture was then heated at 5 °c. After 6 hours, diisopropylethylamine (25 ml, 144 mmol) was added and the mixture was kept at 50 C for an additional 6 hours. The solvent was removed in vacuo and the residue was partitioned between DCM (100 mL) and water (1 mL). The crude product is obtained by separating the liquid phase through a hydrophobic glass and evaporating the organic phase in vacuo. Further purification was carried out using an SPE cartridge (aminopropyl, followed by silica gel) to afford intermediate 72 as a creamy solid (1.24 g). LCMS showed _+==487, · Tret = 2.97 minutes. Intermediate 73 Intermediate 73 is used on the spot in the general procedure for examples 360-414. Also ^'74: ({3·[(ethylamino)methyl]phenyl}methyl)carbamic acid 14-dimethyl 87841-960303-nf3.d〇c -149- 1283678 ethyl ester

The residue was partitioned between EtOAc and water. . The organic phase was dried (MgS04) and evaporated in vacuo. The residue was chromatographed on EtOAc (EtOAc) (EtOAc) Analytical measured values: c, 64 79 ; H, 7 93 ; 1^10.10. (^53⁄42]^3 Requires c, 64 73 ; Η, 7.97 ; Ν, 10.06. MS (M+Na)+301. 75 : N-{[3-(Aminomethyl)phenyl]methyl}acetamide hydrochloride

The ruthenium chloride (4 ml, 4 M) in dioxane was added to a solution of intermediate 74 (1.0 g, 3.6 mmol) in dioxane (10 mL) at 20 ° C The resulting mixture was stirred for 6 hours. The reaction was diluted with EtOAc (20 mL). MSMH+179. iHNMROOOMHz, in d6-DMSO*, 27°C, (5ppm) (5 8.6-8·4 (brm, 3H), 7.38-7.26 (m5 3H), 7·22 (bm, 1H), 4.24 (d, J = 5·7Ηζ, 2H), 87841-960303-中.doc -150- 1283678 3.95 (dd, J = 11.6, 5·7Ηζ, 2H), 1.87 (s, 3H)· Example table instance number Name 1 4-(cyclopentylamino)-1·ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester 2 4-(cyclohexylamino)-1•B Ethyl-1-pyrido[3,4-b]pyridine-5-carboxylic acid ethyl ester 3- 1-ethyl-4-(tetrahydro-2H-piperidinylamino)-1Η-pyrazolo[ Ethyl 3,4-b]pyridine-5-carboxylate 4 4-[(1-methylhexahydropyridin-4-yl)amino]ethylethyl-1H-pyrazolo[3,4_b]pyridine- 5-carboxylic acid ethyl ester 5 4_[(1-ethylhydrazinylhexahydropyridin-4-yl)amino]-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid Ethyl 6 4-(cyclopentylamino)·1_methyl-ih_p than spit[3,4_b]p than y-5-repulsive oxime 7 1-methyl·4_(tetrahydro-2H- Ethyl pyl-4-ylamino)-1 Η-pyrazolo[3,4-b]pyridine-5-carboxylate 8 1-ethyl-4-[(3S)-tetrahydrofuran-3-ylamino -1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester 9 1-ethyl-4-[(3R)-tetrahydrofuran Alkylamino]·1Η·pyrazolo[3,4hepta]pyridin-5-carboxylic acid ethyl ester 10 1-ethyl_4-(tetrahydro-2-indole-thiopiperazin-4-ylamino) -1Η-pyrazolo[3,4-b]pyridine-5-carboxylate ethyl ester 11 1-ethyl-4-(tetrahydrothiophene-3-ylamino)_1H•pyrazolo[3,4_b(10)pyridine _5_Carboxylic acid ethyl ester 12 Earth^cyclopropyl)+ethylpyrazolo[3,4_b]pyridine_5_carboxylic acid ethyl ester 13 '叽,1·tetrahydropyrimidine _3_yl)amine Ethyl 1-ethyl-1H-pyrazolo[3,4-b]pyridinecarboxylic acid ethyl ester 14 4-[(1,1_monotetrahydro-2-H-thiopiperan-4-yl)amine Base]-丨·ethyl_ih_pyridine-5-carboxylate ethyl ester 21 lower group-1·ethyl+(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3, 4-b]pyridine-5-carboxamide 8874l-96〇3〇3-中.doc 151- 22 ' ..... ..... 1·ethyl-N_(4-gasphenyl) 4-(tetrahydro-2Η·jol-4'ylamino)_1H_pyrazolo[3,4-b]pyridine-5-carboxamide 23 N_cyclopentyl-4_(cyclopentylamino) )+ethyl_1H-pyrazolo[3,4_b]pyridine-5-methalamine 24 4_(cyclohexylamino)-N-cyclopentyl-1-ethyl_1H-pyrazolo[3, 4-7&gt;bipyridine-5-carbamidamine 25 N-cyclopentyl-1-ethyl-4-(tetrahydroindol-4-ylamino)_1H~ [3,4-b]pyridine-5-carbamidamine 27 4-[(1-ethylhydrazinylhexahydropyridin-4-yl)amino]cyclopentyl-1-ethyl-1H- 匕 匕 并 [3 , 4-b]p, butyl-5-carbamamine 28 N_cyclopentyl_1_ethyl-5·(tetrahydropyrrole-1-ylcarbonyl)_1H-pyrazolo[3,4-b] Pyridin-4-amine 29 N_cyclohexyl-1-ethyl-5-(tetrahydropyrrole-μ-ylcarbonyl)_1H-pyrazolo[3,4-b]p-precipitate-4-amine 30 1-B -5-5-(tetra-m mouse p-l-l-l-pyrenyl)-N-tetrachloro-2H-forman-4-yl·1Η_ 外匕峻[3,4-b]e ratio -4- Amine 31 4-(cyclopentylamino)ethylidene-N-pyridin-4-ylmethyl)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 32 4-( Cyclohexylamino)·1-ethyl-N-(pyridylmethyl)_1H-pyrazolo[3,4-b]pyridine-5-carboxamide 33 1-ethyl-N-(pyridine bucket Methyl) ice (tetrahydro-2H-piperidin-4-ylamino)_1Η·pyrazolo[3,4-b]pyridine-5-carbamimid 34 4·(cyclopentylamino)- 1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide 35 4-(cyclohexylamino)ethylidene than benzo[3,4-b] -5-Artemisylamine 36 1_ethyl-4-(tetrazine-2H-bromo-4-ylaminol 嗤[3,4_b]p than yttrium- 5-carbamide 39 N-Yuji -4-(cyclopentylamino)-1-ethyl -1H-P is more than [3,4-b]p than pent-5-carbamamine 40 N-benzyl-4-(cyclohexylamino)ethylidene-1H-pyrazolo[3,4 VII]pyridin-5-formamide 41 4-[(1-acetoxyhexachlorop-precipitate-4-yl)amino]]^1_yl-1_1-ethyl_1H-exocarbazole 3,4-b]pyridine-5-methamine amine 87841-960303-中.doc -152- 1283678

42 4-(Cyclopentylamino)ethylidene-indole_(2·ethylbutyl)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 43 4-(cyclohexylamine Small ethyl-N-(2-ethylbutyl)-1Η-pyrazolo[3,4-b]pyrrol-5-cartoamine 44 1-ethyl-N-(2-ethyl Butyl)-4-(tetrahydro-2H-bran-4-ylamino)·1Η-benzazolo-3,4-b]pyridine-5-carboxamide 45 1-ethyl-N- (2-ethylbutyl)-4-[(1-methylhexahydropyridin-4-yl)amino]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide 46 4 -[(1-Ethyl hexahydrop-precipitate-4-yl)amino]-1-ethyl-N-(2-ethylbutyl)-1Η-pyrazolo[3,4-b] Pyridine-5-formamide 47 4-(cyclopentylamino)-1-ethyl-indole (4-phenylphenyl)-1Η-ρ ratio ol[3,4-b] 5-carboxylic acid amine 48 4-(cyclohexylamino)ethylidene-indole-(4.fluorophenyl)-1Η·pyrazolo[3,4-b]pyridine-5-carbamimidium 49 1-B -N-(4-fluorophenyl)-4-[(1-methylhexahydropyridin-4-yl)amino]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide 50 4-[(1-Ethyl hexahydropyridin-4-yl)amino]picethyl-N-(4-fluorophenyl)-1H-pyrazolo[3,4-b]pyridine·5 _Metamine 51 4- (cyclopentylamino)-1-ethyl-hydrazine -propyl-1Η-pyrazolo[3,4-b]pyridine-5-carbamoyl 52 4-(cyclohexylamino)ethylidene-N-n-propyl-1H-pyrazolo[3 ,4-b]pyridine-5-carboximine 53 1-ethyl-N-n-propyl-4-(tetrahydro-2H-pyran-4-ylamino)-1Η-pyrazolo[3 ,4-b]pyridine-5-carboxamide 55 4-[(1-ethylhydrazinohexahydropyridin-4-yl)amino]-1-ethyl-N-n-propyl-1H-pyrazole And [3,4-b]pyridine-5-methanamine 56 N-ylidene-1-ethyl-4·[(1-methylhexahydrop-predative-4-yl)amino]-1H- P is more than [3,4-b]pyridine-5-carbamidamine 57 4-[(1-ethenylhexahydropyridin-4-yl)amino]-1-ethyl-N-(pyridine ice Methyl)-1Η-ρ ratio spit[3,4-b]external b-position-5-methaneamine 61 N-benzyl-4-(cyclopentylamino)-1_methyl-1H- Pyrazolo[3,4-b]pyridine-5-carbamidamine 87841-960303-中. Doc -153- 1283678 62 苄·benzyl-4-(cyclohexylamino)smallmethyl-1H-pyrazolo[3,4-b]pyridine-5-carbamimid 63 N-benzyl-1- Methyl 4-(tetrahydro-2H-piperazin-4-ylamino)-lH-pyrazolo[3,4-b]pyridine-5-carbamimidyl 64 4-(cyclopentylamino) -N-(2-ethylbutyl)小methyl-1H-pyrazolo[3,4-7]pyridine-5-carboxamide 65 4-(cyclohexylamino)-N-(2-ethyl Butyl) small methyl-1H-pyrazolo[3,4-b]pyrrol-5-ylamine 66 汴(2-ethylbutyl)-1-methyl-4-(tetrahydro-2H -pyran-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-methanamine 67 4-(cyclopentylamino)-N-(4-fluorophenyl) 1-methyl-1H-pyrazolo[3,4-b]pyrazole-5-cartoamine 68 4·(cyclohexylamino)-N-(4-fluorophenyl)small methyl·1Η -pyrazolo[3,4-b]pyridine-5-carboxamide 69 N-(4-fluorophenyl)-1•methyl-4-(tetrachloro-2H_pyranyl-4-ylamino) Bis[3,4-b]pyridine-5-carbamide 70 4-(cyclopentylamino)methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide 71 4-(Cyclohexylamino)-1-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide 72 1-methyl winter (tetrahydro-2H-pyran-4 ·Amino)-1Η-pyrazolo[3,4-b]pyridine-5 -Metformamide 74 4·[(1-Ethyl hexahydropyridinyl-4-yl)amino]-N-benzyl small methyl-1H-pyrazolo[3,4-b]pyridine-5- Methionine 76 4-[(1·ethinylhexahydropyridin-4-yl)amino]-N-(2-ethylbutyl)-1-methyl-1H-exo b唆[3, 4-b&gt;Bite-5-Protonamine 78 4-[(1-Ethylhexahydropyridin-4-yl)amino]-N-(4-fluorophenyl)-1·methyl-1H -External 1: also [3,4-b]p than lake -5-carbamamine 81 1-ethyl-N-methyl winter (tetrahydro-2H-piperidinylamino)-1Η·pyridyl Zoxa[3,4-Pentyl-5-carbamimidyl 82 1-ethyl-N,N-dimethyl-4·(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyridyl Zoxao[3,4-b]pyridine-5-carboxamide 83 1-ethyl-N-ethyl-4_(tetrachloro-2H-bran-4-ylamino)-1Η-ρ ratio [3,4-b]pyridine-5-methanamine 87841-960303-中. Doc -154- 1283678 84 1_Ethyl-N-isopropyl_4-(tetrahydro-2H-piperidin-4-ylamino)_111_pyrazolo[3,4-b]p ratio- 5-cartoamine 85 N-benzyl-1-ethyl-4-[(3S)-tetrahydrofuran-3-ylamino]-1H pyrazolo[3,4-b]p than lake-5-formic acid Amine 86 N-benzyl-1-ethyl·4·[(3Κ&gt;tetrahydrofurylamino]-1H-pyrazolo[3,4-7]pyridine-5-carboxamide 87 Ν-mercapto-1- Ethyl_4-(tetrahydrosulfonyl-3-ylamino)-indole-pyrazolo[3,4-b]pyridine-5-carboxamide 88 N-benzyl-4-(cyclopropylamino)- 1-ethylpyrazolo[3,4-b]pyridine-5-carboxamide 89 N·benzyl_4-[(1,1-dihydrotetramethylenesulfonyl-3-yl)amino] Ethyl]-pyrazolo[3,4-b]pyridine-5-carboxamide 90 N-benzyl-4-[(1,1-dihydrotetrahydro-2H-thiopiperan-4) Amino]-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide 91 N-benzyl_1_ethyl-4-(tetrahydro-2H-thio Shouting _4·ylamino)-1Η-pyrazolo[3,4-b]p than lake-5-cartoamine 92 1·ethyl-N-(4-fluorophenyl)-4-[ (3S)-Tetrahydrofuran-3-ylamino]·1Η-pyrazolo[3,4-b] hydroxyp--5-cartoamine 93 1-ethyl-N-(4-fluorophenyl)- 4-[(311)_tetrahydrofuran-3-ylamino]-1H-pyridyl And [3,4-b]p is more than 5-aminoamine 94 1·ethyl-N-(4-fluorophenyl)_4_(tetrahydro-2H-thiopyran-4-ylamino) -1Η-pyrazolo[3,4-b]pyridine-5-formamide 95 1-ethyl-N-(4-fluorophenyl)-4·(tetrahydro-p-s-phen-3-ylamino ) _ih-p is more than [3,4-b] outer bite · 5 · methotrexate 96 4- (cyclopropylamino) small ethyl-fluorene-(4_fluorophenyl)_1Η_pyrazole [ 3,4-b]pyridine- 5-carbamamine 97 4_[(1,1_dihydrotetramethylene-4-yl)amino]-i-ethyl_N_(4-fluorophenyl) _ 1H-pyrazolo[3,4-b]pyridine-5-formamide 98 4-[(1,1-dihydrotetrahydro-2H·thiopyran-4-yl)amino]-1 · Ethyl·Ν_(4_fluorophenyl)-1Η4 is also [3,4_b]p is more than 5--5-carbamamine 87841-960303-. Doc -155- 1283678 Example No. Name 100 1-Ethyl-N-[4-(methyl sulphonyl) aryl] 4-(tetrahydroendan-4-ylamino)-1Η-pyrazole[3 , 4-b]pyridine-5-carboxamide 101 (1-{[1_ethyl ice (tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-7] Mouth-butyl-5-yl]carbonyl}hexahydroindole-3-yl)methylaminocarbamic acid tert-butyl ester 102 1-ethyl·Ν_[3-(methicic acid)octyl]-4 -(tetrahydro-2H-fluoren-4-ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide 103 1-ethyl_5-{[5-methoxy -6-(trifluoromethyl)-2,3-dihydro-1H-acidyl-1-yl]}}N-hydrogen-2H-pyran-4-yl-1H-P ratio And [3,4-b]indole-4-amine 104 N_[(5-chloropyridin-2-yl)methyl]·1_ethyl-4-(tetrahydro-2H-pyran-4) Amino)·1Η_pyrazolo[3,4-b]pyridine-5-formamide 105 N_(4-fluoroindolyl)-1_ethyl-N-isopropyl-4_(tetrahydro- 2H-Flan-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 106 N-(3-chlorobenzyl)-1-ethyl_N_(2 -Hydroxyethyl) Winter (tetrahydro-2H-pyran-4-ylamino) than spit[3,4_b]p is more than decylamine 107 1-ethyl_N_[(5-methyl-3- Phenylisoindole _4_yl)methyl]-4-(tetrahydro-2H -piperazin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carbamimidyl 108 Ν-(2·t-butoxyethyl) small ethyl-4 ·(tetrahydro 2 Η· shout-4-ylamino)-1Η-ρ ratio 并[3,4-b]p than pent-5-cartoamine 109 1-ethyl-4-(tetrahydrogen) -2H-pyran-4-ylamino)-indole-(1,3-pyrazol-2-ylmethyl)-lH-ρ ratio also [3,4-b]p than y-5-A Indoleamine 110 1-ethyl-N-sevenidine _4_ylmethyl)-4-(tetrahydro-2H-pyran-4-ylamino)-1Η-mouth ratio and [3,4-b ]p butyl-5-cartoamine 111 1·ethyl-N-[(2-methylthiazol-4-yl)methyl]_4_(tetrahydro 2 Η 4 _ 4 4 ylamino)-1 Η- ρ 比吐和[3,4-b]p 比盐-5_Metformamide 112 N_[3-(T-butoxymethyl)-yl]-diethyl-4-(tetrahydro-2H_喃 -4- 基 基 基 基 基 ρ ρ ρ [ [3,4-b> 淀 -5 -5-carbamide 113 1-ethyl- Ν · {2-[methyl (methylsulfonyl) amine Ethyl]ethyl}-4_(tetrahydro-211-pyran-4-ylamino)_1Η_ρ than spit[3,4-b]p than lake-5-formamide 114 1·ethyl·Ν- (ρ whistle 1 _2·ylmethyl)-4-(tetrahydro-2H-fluoren-4-ylamino)-1Η-exopurin and [3,4-b]indole-5-carboxylic acid amine 87841-960303-中. Doc -156- 115 1-ethyl-5-{[4-(pyridin-2-ylcarbonyl)hexahydropyrrolidin-1-yl]carbonyl}-N-tetrahydro-2H-pyran-4-yl- 1H-pyrazolo[3,4-b]pyridin-4-amine 116 N-(2-chloro-6-fluorobenzyl)ethylidene-4_(tetrahydro-2H-pyran-4) Amino)-1Η-pyrazolo[3,4-b]pyridine-5-carbamimidamine 117 1_ethyl-N_[(6-paid base_1,6_two-mouse p-predyl-3-yl) )methyl]-4-(tetrachloro-2H-cyclopentan-4-ylamino)-1Η-ρ is more than [3,4-b]p than pent-5-cartoamine 118 N-[ 3-(Aminocarbonyl)benzyl]sodiumethyl 4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo P,4-b]pyridine-5-carboxamide 119 1-ethyl-N-{4-[(methylamino)carbonyl]phenyl b 4-(tetrahydro-2H-piperanylamino)-1Η·pyrazolo[3,4_b]pyridine-5 -Procarbamide 120 1-ethyl-N-[2-(l-methyl·1Η-味吐-4_yl)ethyl]-4-(tetrazo-2H_ brityl 4-ylamino -1Η-pyrazolo[3,4-b]pyridine-5-methanamine 121 N-{2-[(anilinylweiyl)amino]ethyl}-1-ethyl_4-(four Hydrogen-2H- 喊 _ 4-ylamino)-1 Η-pyrazolo[3,4-b]pyridine_5-formamide 122 1-ethyl-N-(1H-tetras-5-yl) Methyl)-4-(tetrazo-2H-monopyran-4-ylamino)-1H·pyrazolo[3,4-b Pyridine-5-carbamide hydrochloride 123 I-ethyl-4-(tetrazine-2H-bran-4-ylamino)-oxime-[2-(1Η-1,2,4-three嗤·1_yl)ethyl]-1Η·pyrazolo[3,4-b]pyridine-5-formamide 124 2-[{[1-ethyl-4·(tetrazo-2H- brim) 4_ylamino-based ton[3,4-b]pyridin-5-yl]carbonyl}(methyl)amino]ethylaminocarbamic acid tert-butyl ester 125 1-ethyl-4-(four Η-2Η_ρ底喃-4-ylamino)-N_[4_(trifluoromethyl)phenyl]- 1H-pyrazolo-; 3,4-b]pyridine-5-carboxamide 126 4_( {[1-ethyl-4-(tetrazol-2H-bromo-4-ylamino)-1Η-ρ is more than [3,4-b] pyridinium-5-yl]carbonyl}amino) Hexahydro-p-precipitate small-reactive acid third-butyl ester 127 1-ethyl-Ν-{3-[(A)-amino-propyl]-4-(tetrahydro-2-indole-branches _4 · Amino group)-1Η_External b spit [3,4-b]External b-precipitate-5_Artemisamine 128 N-[2_(Dimethylamino)-yl]Sodiumethyl_4_(tetrahydrogen) Η2 - ϊ 喃 -4-ylamino) Η 1 Η-pyrazolo[3,4-b]pyridine _5-formamide 129 1-ethyl-fluorene-[(1·ethyltetrahydro ρ Bilo-2·yl)methyl]-4-(tetrahydro-2H-fluoren-4-ylamino)-1Η-ρ ratio spit [3,4-b> butyl--5-carbamide 130 1-ethyl-N-(tetrahydrofuran-2-ylmethyl) )-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η·pyrazolo[3,4-b]pyridine-5·carbamamine 87841-960303-中. Doc -157- 131 1-Ethyl-N-tetrachloro-2H-pyranyl 4-yl-4-(tetrachloro-2H-bungan-4-ylamino) 1Η-pyrazolo[3,4 -b]pyridine-5-carbamamine 132 N-{4_[(dimethylamino)sulfonyl] aryl} winter ethyl (tetrahydro-2H-piperidin-4-ylamino)-1Η -pyrazolo[3,4-b]pyridine-5-carboxamide 133 1-ethyl_N-{3-[(methylsulfonyl)amino]benzyl}-4-(tetrahydro-2H -piperazin-4-ylamino)-1Η&gt; ratio also [3,4-b]external b-position-5-formamide 134 M[l-ethyl-4-(tetrahydro-2H-pyran 4-ylamino)·1Η-pyrazolo[3,4_b]pyridine-5-yl]carbonyl}hexahydropyridine-2-carboxamide 135 1-ethyl-N-(4-methoxyphenyl ) ice (tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazine and [3,4-b> butyl--5-formic acid amine 136 1-ethyl-Ν-[3·(2 ·Ketyltetrahydropyrrole-1_yl)propyl]-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-ρ than spit[3,4-b]p ratio- 5-cartoamine 137 1-ethyl-N-[2-(l-methyltetrahydropyrrole-2-yl)ethyl]-4-(tetrahydro-2H-pyran-4-ylamino) -1Η-ρ比峻和[3,4-b]p 比淀-5-甲含胺138 1-ethyl-Ν-(ρ比淀-3-ylmethyl)-4_(tetrachloro-2H- Shouting -4_ylamino)-1Η·pyrazolo[3,4-b]pyridine-5-formamidine 139 1_Ethyl-N-(l-methylazide external b-butyl-4-yl)-4-(tetrachloro-2H-pyro- 4-ylamino)-1Η-pyrazolo[3, 4-b]pyridine_5_formamide 140 1-ethyl-N-(l-ethylpropyl)-4-(tetrahydro-2H-piperidin-4-ylamino)_1H-pyrazole [3,4-b]pyridine-5-formamide 141 1-ethyl-N-(2-hexachloro-p-pred-1-ylethyl)-4-(tetrazine-2H- shouting-4 -ylamino)-1Η_ρ than wow and [3,4_b]p than yt-5·ylamine 142 1-ethyl-N-(3-isofo-4-ylpropyl)-4_(four gases ·2Η_叫喃-4-ylamino)-1Η-^ sniff [3,4~b]p than yt-5·enamin 143 N-(3-ethoxypropyl)-1-B 4-(tetrahydropyran-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 144 N-(cyclohexylmethyl)succinyl-4- (tetrahydro-2H-fluoren-4-ylamino)-1Η-ρ-pyrazolo[3,4-b]pyridine-5-carboxamide 145 N-[3_(dimethylamino)propyl] -1·ethyl phenyl (tetrahydro-2H-piperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carbamimid 146 1-ethyl-N-new Pentyl-4-(tetrachloro-2H· shoutin-4_ylamino)-1Η-^ than spit[3,4-b]p than lake-5-formamide 87841-96〇3〇3 ·in. Doc -158 - 1283678 147 1-ethyl-indole (4-methoxy-yl)-4-(tetrahydropyran-4-ylamino)-1Η-pyrazolo[3,4_b]pyridine_ 5_Metformamide 148 1-ethyl·Ν_{2·[(benzoic acid)amino]ethyl}-4-(tetrahydro-2H-furan-4-ylamino)·1Η-pyrazole And [3,4-b]pyridine-5-formamide 149 N-[2-(ethylguanidino)ethyl]sodiumethyl 4-(tetrahydro-2H-pyran-4-ylamino) -1H-pyrazolo[3,4_b]pyridine-5-carboxamide 150 1-ethyl-N-{2_[(methyl succinyl)amino]ethyl}-4-(tetrahydro-2H «^Butyl-4-ylamino)-1Η-ρ is more than [3,4-b]p than pent-5-cartoamine 151 1·ethyl-N-methyl-N-(p ratio 44_ylmethyl)-4-(tetrahydro-2H-pyran-4-ylamino group than spit [3,4-b>pyridin-5-carbamide 152 1-ethyl-hydrazine ·{2·[(2-methoxyphenyl)(methyl)amino]ethyl b 4-(tetrahydro-2H-pyran-4-ylamino)-1Η-ρ is more than [3, 4-b]p-precipitate-5-formamide 153 1-ethyl-N-(2-keto-2-phenylethyl)-4-(tetrahydro-2H-pyran-4-ylamine -1H-p is more than [3,4-b]p than _5_cartoamine 154 N-(2,5-difluorobenzyl)succinyl-4-(tetrahydro-2H- Piperan-4-ylamino)_1H_pyrazolo[3,4-b]pyridine-5-carboxamide 155 1_Ethyl_4-(tetrahydro-2H-piperidin-4-ylamino)-N-[4-(trifluoromethyl)-yl]-lH-p ratio [3,4_b&gt;碧丁-5_Mercaptoamine 156 N,l-Diethyl-N-propyl-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4- b]pyridine-5-methanamine 157 N-cyclopropyl_1_ethyl-4-(tetrahydro-2H&gt;anthracen-4-ylamino)-1Η-ρ ratio 并[3,4- b] Pyridine-5-formamide 158 N-(2-Amino-2-ketoethyl)-1_ethyl_4_(tetrahydro-2H-furan-4-ylamino)-1Η- Pyrazolo[3,4-b]pyridine-5·carbamidamine 159 1-ethyl-N-(3-methoxyphenyl)-4_(tetrahydro-2H-pyran-4-ylamino) _ih-pyrazolo[3,4-b]pyridine-5-carboxamide 160 N-(3,4-difluoroaryl)·1_ethyl-4-(tetrahydro-2-indolyl-4 _i-amino))iH-pyrazolo[3,4-b]pyridine-5-formamide 161 3-({[1-ethyl-4-(tetrahydro-2H-pyran-4-ylamine) Base)_1Η·pyrazolo[3,4-b]exodecyl-5-yl]carbonyl}amino)propionic acid ethyl ester 162 N-(l_mercapto 7T to bit-4-yl)-1- Ethyl-4-(tetrahydro-2H-cyclobutanyl 4-amino-amino)-1Η-pyrazolo[3,4-b]pyridine-5-decylamine 87841-960303-中. Doc -159- 1283678 163 N-butyl-4-{[l-ethyl-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b] Pyridin-5-yl]carbonyl}hexahydropyrazine small formamide 164 1-ethyl-4·(tetrahydro-2H-piperidin-4-ylamino)-indole-(1,3,4-pyrimidine Diazol-2_yl)_ 1H-pyrazolo[3,4h7]pyridin-5-formamide 165 (·(2,3-dichloro-1H- isomer·2-yl)_1_ethyl- 4-(tetrachloro-2H-pyran-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 166 1_ethyl-N-[2-(2 -ketoimidazolinidin-1-yl)ethyl]-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5- Indoleamine 167 N-(3,4-dimethoxybenzyl)ethylethyl-4-(tetrahydro-2Ημpyran-4-ylamino)-1Η·pyrazolo[3,4_b]pyridine- 5_Metamine 168 N-(3-chloro-aryl)-1-ethyl_4-(tetrazo-211-0 guar- 4-ylamino)-111-0 is more than [3,4 -b]pyridine-5-decylamine 169 1-ethyl-5-[(4·methylhexahydropyrrolidin-1-yl)carbonyl]_N_tetrahydro-2H-piperidinyl-1H-pyridyl Zydro[3,4-b]pyridin-4-amine 170 1-ethyl-N-(2-ethyl)-4((tetrachloro-2H-chloropyran-4-ylamino) ,4-b]pyridine-5-formamide 171 1-ethyl-5-{[4-(4-methoxybenzene) Hexahydropyranin-1-yl]carbonyl}-N-tetrahydro-2H-piperidin-4-yl-1H-pyrazolo[3,4-b]pyridine-4_amine 172 1-ethyl- N-{4-[(methylsulfonyl)methyl]phenyl}-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-ρ is more than [3,4_b] external b Bite-5_carbamamine 173 N-[3-(dimethylamino)-3-ketopropyl]sodiumethyl 4-(tetrahydro-2H-piperidin-4-ylamino)-1Η -ρ ratio vomit [3,4-b] outer b-position-5-formamide 174 1-ethyl_N-[(1-methyl-1H-imidazol-5-yl)methyl]-4- (tetrahydro-2H-piperazin-4-ylamino HH-pyrazolo[3,4-b]pyridine-5-carbamimid 175 1-ethyl-N-{4_[(methylamino) Thiophene]phenyl 4-(tetrahydro-2H-piperazin-4-ylamino HH-pyrazolo[3,4-b]pyridine-5-formamide 176 N_(2-chloroethyl )_1_Ethyl_4-(tetrachloro-2H-l-amyl-4-ylamino)-1Η-b-pyrazolo[3,4-b]pyridine-5-formamide 177 1-ethyl- N-methyl-N-[(5-methyl-1,3,4·oxadiazol-2-yl)methyl]-4-(tetrahydro-2H-bran-4-ylamino)_1H -pyrazolo[3,4-b]pyridine-5-formamide 178 1-ethyl-indole-[(1·methyl-1H-pyrazol-4-yl)methyl]-4-(four Hydrogen-2Ημ派喃-4_ylamino)_1Η-pyrazolo[3,4-b]pyridine-5-formamide 87841-960303-中. Doc -160- 1283678 179 1-Ethyl-N-methyl-indole-[(1-methyl-1H-imidazol-2-yl)methyl]-4-(tetrahydro, 2H- brim-4- Amino-based)-iH-pyrazolo[3,4-b]pyridine-5-carboxamide 180 1-ethyl-4-(tetrahydro-2H-piperidin-4-ylamino)-N- (2-pyrimidin-2-ylethyl)-1H-pyrazolo[3,4-7]pyridine-5-carboxamide 181 Ν-[2·(4-chlorophenyl)ethyl]-1- Ethyl ice (tetrahydro-2H-piperazin-4-ylamino)_ 1Η-ρ ratio spit [3,4-b]p ratio far-5-cartoamine 182 1-ethyl-Ν·[ 2-(2-methoxyphenyl)ethyl]·4·(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine_5_ formazan Amine 183 4-(cyclohexylamino)_1-(3-ethoxy-3-ketopropyl)-1 Η-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester 185 1- N-propyl-4-(tetrachloro-2H-»1 phenan-4-ylamino group is more than [3,4-b]p than pyridine-5-carboxylic acid ethyl ester 186 1-(2-hydroxyl Ethyl)-4-(tetrahydro-2H-pyran-4-ylamino)-1Η-pyrazolo[3,4-7]pyridine-5-carboxylic acid ethyl ester 187 N-[4_(methyl-acid Base]_1_正-propyl-4-(tetrahydro-2H_ shout-4-ylamino)_1H-pyrazolo[3,4-b]pyridine-5-carboxamide 188 N -(4-fluorophenyl) small n-propyl-4-(tetrahydro-2H-pyran-4-ylamine )·ΗΗ-ρ-pyrazolo[3,4-b]pyridine-5-formamide 189 1·ethyl-6-methyl_4-(tetrahydro-2H-pyranyl-4-ylamino) 1-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester 190 4-(cyclohexylamino)-1-ethyl-6-methyl-[3,4-b]p ratio盐-5- 叛 酉 酉 191 4-(cyclohexylamino)-1•ethyl-6-methyl-N-[4-(methyl sulfhydryl) aryl]pyrazole[3,4- b] Pyridin-5-formamide 192 N-yote·4-(cyclohexylamino)-1-ethyl-6-methyl-1H-P than spit[3,4-b] -5-Artemisamine 193 4-(cyclohexylamino)ethylidene-N-(4-fluorophenyl)·6-methyl-1H-1T ratio also [3,4_b]external ti- 5-Methylamide 194 4-(cyclohexylamino)-1·ethyl-6·methyl-[4-(trifluoromethyl)-yl]1Η-pyrido[3,4-b] p 比盐-5-甲含胺195 4-(cyclohexylamino)_N-(2,3-dihydro·1Η_ although-2-yl) small ethyl methylpyrazolo[3,4- b] Pyridine-5-formamide 87841-960303-中. Doc •161- 1283678 196 N-Mercapto-1·ethyl-6-methyl_4-(tetrahydro-2H-pyran-4-ylamino)-1Η-pyrazolo[3,4-b Pyridine-5-carbamamine 197 N-ylidene-1-ethyl-4-[(2·费基一氮七圜健-3-yl)amino]-lH-p-pyrazole[3, 4-7]pyridin-5-formamide 198 Ν·benzyl-1-ethyl-4·[(3-hydroxycyclohexyl)amine; ΜΗ-pyrazolo[3,4-b] p-precipitate- 5-mercaptoamine, also known as N-Germanyl-1-ethyl-4-[(3-carbyl hexane small)amino]-1Η-pyrazolo[3,4-b]pyridine -5-Mergamine 199 N·indolyl-1·ethyl-4-[(4-hydroxycyclohexyl)amino]-1H-pyrazolo[3,4-b] 1 (7 than D-5 - formic acid amine, also known as N-mercapto-1-ethyl-4-[(4- ricottine propyl)amino]-1 Η-pyrazolo[3,4-b]pyridine-5 -carbamamine 200 N-benzyl-1-ethyl-4-[(3-hydroxycyclopentyl)amino]_1H-pyrazolo[3,4-b] p than ammonium-5-formate, Also known as N-mercapto-1-ethyl-4-[(3. sylylene pentane) amino]-1 Η-pyrazolo[3,4-b]pyridine-5- formazan Amine 201 N_benzylic small ethyl sorb [(4-ketocyclohexyl)amine; MH-pyrazolo[3,4_b] p than pent-5-cartoamine, also known as N-fluorenyl- 1_ethyl-4-[(4-fluorenyl J curtain) Alkyl) Amino]_1H-pyrazolo[3,4-b]pyridine-5-carboxamide 202 1-ethyl-N-(2-hydroxysodiummethylethyl)-4-(tetrahydrogen) -2H-piperidinylamino)-1Η-pyrazolo[3,4-b]pyridine-5·carboxamide 203 (2S)-2-({[l-ethyl-4-(tetraz) -2H-Bucer-4-ylamino)-1Η-ρ than spit [3,4-b]pyridin-5-yl]carbonyl}amino)-3-hydroxypropanoic acid methyl ester Example No. Name 204 1 -ethyl 4-[(4-hydroxycyclohexyl)amino]-1H-pyrazolo[3,4-7]pyridine-5.carboxylic acid ethyl ester 205 1-ethyl 4-[(4-keto ring) Ethyl)amino]-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester 207 4·[(1-ethylindenyl-4-hexahydropyridinyl)amino]-1- Ethylethyl 1-H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester 209 4-[(4-Aminocyclohexyl)amino]-1-ethyl-1Η·pyrazolo[ 3,4_b]pyridine-5-carboxylate ethyl ester 8784l-96〇3〇3-中. Doc -162- 1283678 210 Ethyl-N-[(1-oxo-3-pyridyl)methyl]_4_(tetrahydro-2H-piperidinylamino)-1Η-pyrazolo[3,4- b]pyridine-5-carbamimid 211 1·ethyl-N-[(l-oxy-2-pyridyl)methyl]dong (tetrahydro-2-indole-piperidinyl)-1Η-pyrazole And [3,4-b]pyridine-5-formamide 212 1-ethyl-indole-[(1. oxidized-4-exo b-decyl)methyl M-(tetrahydro-2H-pyran-4 -ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carbamimidyl 214 4-[(cis-4-aminocyclohexyl)amino]xiaoethyl good (phenyl Methyl &gt; 1H_pyrazolo[3,4-b]pyridine-5-formamide 221 4·(cyclobutylamino)ethylidene(phenylmethyl)_1H-pyrazolop,4_b Pyridine-5-formamide 222 4-(cycloheptylamino)ethylidene(phenylmethyl)_1Η-ρ than oleno[3,4-b]^pyridin-5-carboxamide 223 1-ethyl-4-[(4-methylcyclohexyl)amino]-N-(phenylmethyl)-iH-pyrazolo[3,4-7]pyridine-5-carboxamide 224 1 -ethyl-4-[(3-methylcyclohexyl)amino]-indole-(phenylmethyl)-iH-pyrazolo[3,4-b]pyridine-5-carbamimid 225 1- Ethyl-4-[(l-methyl-trihexyl)amino](phenylindole-based ton[3,4-b]pyridine-5-formamide 226 4 -[(lR, 2R, 4S)-bicyclic and [2. 2. 1]hept-2-ylamino]-1-ethyl-N-(phenylmethyl)-1Η·pyrazolo[3,4-b]pyridine-5-formamide 227 4-[(lR , 2S, 4S) _ double loop and [2. 2. 1]hept-2-ylamino H-ethyl-N-(phenylmethyl)-1Η-pyrazolo[3,4-b]pyridine-5-carbamimidyl 228 1-ethyl-4- {[(3S)-2-keto-3-tetrahydropyrrolyl]amino}_N-(phenylmethyl)_1H-pyrazolo[3,4-b]pyridine-5-carboxamide 229 4 -[(2,5-diketo-3-tetraoxapyrryl)amino]-1-ethyl-N-(phenylmethyl)-1H-pyrazolo[3,4-b]pyridine- 5-Protonamine 230 4-(1-Azabicyclo[2·2·2]oct-3-ylamino)-1·ethyl-N-(phenylmethyl)-1H-pyrazolo[3 , 4-b]pyridine-5-formamide 231 1-ethyl-4-[(l-methylcyclohexyl)amino]-indole·{[4-(methoxy)phenyl]methyl} -1Η-pyrazolo[3,4-b]pyridine-5-carbamimid 233 4-(cyclobutylamino)ethylidene-N_{[4-(methoxy)phenyl]methyl b 1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 87841-960303·中. Doc -163- 1283678 234 4-(cycloheptylamino)ethylidene_N-{[4-(methoxy)phenyl]methyl}_ιη·pyrazolo[3,4-b]pyridine- 5-Protonamine 235 4-[(lR,2R,4S)-bicyclo[2·2·1]heptan-2-ylamino H-ethyl-anthracene {[4-(methoxy)benzene Base]methyl}_1H# is more than [3,4_b]p than lake-5_formamamine 236 1-ethyl4-[(4-methylcyclohexyl)amino]-N-{[4- (Methoxy)phenyl]methyl is more than [3,4-b]p than ammonium 5-carboxylate 237 1-ethyl-4-[(3-methylcyclohexyl)amino]-N -{[4-(Methoxy)phenyl]methyl}-1Η-pyrazolo[3,4_b]pyridine·5-formamide 238 4-[(lR,2S,4S)-bicyclo and ρ· 2·1]heptan-2-ylamino]picethyl-indole-{[4-(methoxy)phenyl]methyl}-1Η-pyrazolo[3,4-b]pyridine-5- Methotrexate 239 4-[(cis.4-aminocyclohexyl)amino]ethylidene-N-{[4-(methoxy)phenyl]methyl}-1Η-external b-[ 3,4-b&gt;Bite-5-Protonamine 240 4·(Cycloheptylamino)-1·ethyl-Ν·({4-[(methylsulfonyl)amino]phenyl} A Base)-1Ημ ratio also [3,4-b]p ratio _5_methalamine 241 4-(cyclobutylamino)-1·ethyl-Ν·({4_[(methylsulfonyl) Amino]phenyl}methyl)-1Η-ρ Comparative 唆[3,4-b]pyrazine-5-formamide 242 4-[(lR,2R,4S)-bicyclic and P. 2. 1]hept-2-ylamino]-1-ethyl-N-({4-[(methylsulfonyl)amino]phenyl}methyl)-1Η-pyrazolo[3,4-b Pyridine-5-formamide 243 4-[(lR,2S,4S)·bicyclo[2_2. 1]hept-2-ylamino]picethyl-N-({4_[(methylsulfonyl)amino]phenyl}methyl)-1Η-pyrazolo[3,4-b]pyridine- 5-Proline 244 1 1-ethyl-4-[(4·methylcyclohexyl)amino]-Ν-({4·[(methylsulfonyl)amino]phenyl}methyl)-1Η- Bamboo b also [3,4-b]r than lake-5-cartoamine 245 1·ethyl_4_[(3-methylcyclohexyl)amino]·Ν-({4-[(methylsulfonate) Indenyl)amino]phenyl}methyl)·1Η-ρ is more than [3,4-b]p than pent-5-ylamine 247 1-ethyl-4-[(l-methyl ring) Hexyl)amino]-N_({4_[(methylsulfonyl)amino]phenyl}methyl is more than spit[3,4-b]p than _5_甲甲胺2484-[(顺4-Aminocyclohexyl)amino]-1-ethyl-N-({4-[(methylsulfonyl)amino]phenyl}methylpyrano[3,4-b]p Bismuth-5-formic acid amine 249 4-(cyclohexylamino)-1-ethyl-N-({4-[()-amino)phenyl}methyl)-1H-P ratio And [3,4-b]p is more than 5-aminoamine 250 4-(cycloheptylamino)-indole-(2,3·dihydro-1H-but-2-yl)-1-B Base-1H-P is more than [3,4-b]pyridine-5-formamide 87841-96〇3〇3_. Doc •164- 1283678 251 4-(Cyclobutylamino)-N-(2,3-dihydro-1H-indol-2-yl)-1-ethyl·1Η-pyrazolo[3,4- b]pyridine-5-methanamine 253 N-(2,3-diaza-1H-indox-2-yl)·1-ethyl-4-[(3-methylcyclohexyl)amino]_ 1Η -pyrazolo[3,4-b]pyridine-5-carboxamide 254 N-(2,3-dihydro-1H- although -2.yl)-p-ethyl 4-[(4-methylcyclo) Hexyl)amino]-IH-p is more than [3,4-b]W: yt-5-carbamide 255 4-[(lR,2R,4S)-bicyclo[2·2·1]g Amino]]N-(2,3-dihydro-1H-indol-2-yl)-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide 256 4- [(lR, 2S, 4S)-double soil and [2·2·1]heptylamino]-N-(2,3-dichloro-1H- is-2-yl)-1•ethyl-1H ·pyrazolo[3,4_b]pyridine-5-formamide 257 Ν·(2,3-dihydro-1H-indol-2-yl)sodiumethyl-4-[(l-methylcyclohexyl) Amino]-lEMb gorge[3,4-b]p is more than 5-amylamine 258 4-[(cis.4-aminocyclohexyl)amino]-N-(2,3-di Hydrogen-1H-indol-2-yl)sodiumethyl-1H-pyrido[3,4-b]p than yt-5-carbamide 259 1_ethyl-N-{4-[(methane) Mercapto)methyl]phenyl}·4-[(4-ketocyclohexyl)amino]-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 260 N- [(2,4-dimethylphenyl)methyl]-1-ethyl winter [(4. ketocyclohexyl)amino]-1H-pyrazolo[3,4_b]pyridine-5- formazan Amine 261 Ν_[(3,4·dimethylphenyl)methyl]sodiumethyl-4-[(4-ketocyclohexyl)amino]-lH-p-pyrazolo[3,4-b] Pyridine_5_formamidine 262 N-[(3,4-dichlorophenyl)methyl]-1-ethyl_4-[(4-ketocyclohexyl)amino]-1H-pyrazole [3,4-b]pyridine-5-formamide 263 1_ethyl-N-{[4-(methoxy)phenyl]methyl b 4_[(4-ketocyclohexyl)amino] -1H-pyrazolo[3,4-b]pyridine_5-formamide 264 1-ethyl-N-({4-[(methylsulfonyl)amino]phenyl}fluorenyl)-4_ [(4-Ketylcyclohexyl)amine HH_p is more than spit[3,4-b]externate-5-formamide 265 N-{[4-(dimethylamino)phenyl]methyl b Μethyl_4-[(4-ketocyclohexyl)amino]-lH-p is more than [3,4-b]p than _5_carbamamine 266 N-({4-[( Difluoromethyl)oxy]phenyl}methylethyl winter [(4-ketocyclohexyl)amino]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide 267 1 -ethyl-4-[(4-ketocyclohexyl)amino]]ν·{[4-(trifluoromethyl)phenyl]methylHH-pyrazolo[3,4-blpyridine- 5. Myramine 87841-960303-中. Doc-165- 1283678 268 1-Ethyl-N-{[4-(methylsulfonyl)phenyl]methyl}·4-[(4-ketocyclohexyl)amino]-1Η-pyrazole [3,4-b]pyridine-5-formamide 269 1-ethyl-N-(4-fluorophenyl)·4-[(4-fluorenylcyclohexyl)amino]-1H_p ;3,4-b]pyridine-5-carbamimid 270 1-ethylidene [(4-ketocyclohexyl)amino]-N-(2-pyridylmethyl)-1Η-pyrazolo[ 3,4_b]pyridine-5-carbamidamine trifluoroacetate 271 N-(2,3-dihydro-1H-indole-2-yl)ethylethyl-4-[(4-ketocyclohexyl)amine -1H-pyrazolo[3,4-b]pyridine-5.carbamamine 272 N-(l-ethinyl-4-hexahydropyridinyl)-1-ethyl-4-[(4 -ketocyclohexyl)amino]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide 273 1-ethyl-N_[(l-methyl-1H-pyrazole-4- Methyl]-4-[(4-ketocyclohexyl)amino]·1Η-pyrazolo[3,4-b]pyridine-5·carboxamide 274 N,l-diethyl_4 -[(4-ketocyclohexyl)amino]-1H-pyrazolo[3,4-b]pyrodo-5-cartoamine 275 1-ethyl-4-[(4-ketocyclohexyl) Amino]-N-(l,3-oxazol-2-ylmethyl)-1Η-p is more than [3,4-7] than dian-5-carbamide 276 1-ethyl-N_ (phenylmethyl)-4-(tetrahydro-2H_per pipe喃-3-ylamino)·1Η-pyrazolo[3,4-b]pyridine-5-formamide 277 N-({4-[(difluoromethyl)oxy]phenyl}methyl -1_ethyl_4_(tetrahydro-2H-pyranyl-3-ylamino)-1Η_ρ ratio also [3,4-b> butyl-5-nonylamine 278 1-ethyl-4 -(tetrahydro-2H-piperidin-3-ylamino)_N-{[4-(trifluoromethyl)phenyl]methyl}-1Η_external b spit [3,4-b> ratio -5-5-Metaguanamine 279 1-ethyl-N-{[4-(methylsulfonyl)phenyl]methyl}-4-(tetrahydro-2H-indol-3-ylamino)_1H -pyrazolo[3,4-b]pyridine-5-formamide 280 1-ethyl-N_{4·[(methylsulfonyl)methyl]phenyl b 4-(tetrahydro-2H-indole喃-3-ylamino)-1Η-pyrazolo[3,4_b]pyridine_5-formamide 281 1-ethyl-N-(4-fluorophenyl)-4-(tetrahydro-2H- Piperidin-3-ylamino)-1Η-pyrazolo[3,4-b>pyramid-5-formamide 282 1-ethyl-N-(2-pyridylmethyl)-4-( Tetrahydro-2H-piperidin-3-ylamino)·1Η-pyrazolo[3,4-b]pyridine-5-formamide trifluoroacetate 283 Ν·(2,3·dihydro-1H -mercapto)-1_ethyl_4_(tetrahydro-2H-bromo-3-ylamino)-1Η-pyrazolo[3,4-b]pyridine_5-formamide 87841-960303- in. Doc -166 - 1283678 284 N-(l-Ethyl-4-ylτ nitrogen p-precipitate)-1-ethyl-4-(tetrachloro-2Η-ϊ派喃_3_ylamino)_1H- Pyrazolo[3,4-b]pyridine-5.carbamamine 285 1-ethyl-N-[(1-methyl-1H-pyrazol-4-yl)methyl]-4-(tetrahydrogen) _2H_ shouting _3_ arylamino)_1H-pyrazolo[3,4-b]pyridine-5-carboxamide 286 N,l-diethyl-4-(tetrahydro-2H- britant- 3-aminoamino)_1Η-ρ ratio ol[3,4-b] 1 (7 than bite-5-cartoamine 287 1-ethyl-4_(tetrahydro-2H-nican-3-ylamine) -N-(l,3-psec-2-ylindenyl)_ 1H-pyrazolo[3,4-b]pyridine-5-carboxamide 288 4_[(4,4-difluoro Cyclohexyl)amino]·1-ethyl-N-(phenylmethyl)-lH-pyrazolo[3,4-b]pyridine-5-carboxamide 289 1-ethyl-4-[(4 ·Fluoro-3-cyclohexan-1-yl)amino]-N-(phenylmethyl)_1H_pyrazolo[3,4-b]pyridine-5-carboxamide 290 4_[(1- Acetyl-4-hexahydropyridyl)amino]·Ν-(2,3-dihydro-1H·indol-2-yl)-1-ethyl-1Η-Ρ比哇和[3,4- b]p-precipitate-5-formic acid amine 291 4-[(1-ethylindolyl-4_hexahydropyridinyl)amino]-indole-[(3,4·dichlorophenyl)methyl] Base-1Η-pyrazolo[3,4-b]pyridine_5_methamine 292 4-[(1-acetamidine) 4-tetrahydropyridyl)amino]-1-ethyl-N-[(3-fluorophenyl)methyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide 293 4-[(1·Ethyl-4-pyropyridyl)amino]-N-[(3,4-difluorophenyl)indolyl]-1_ethyl-1H-pyrazolo[ 3,4-b]pyridine-5-methanamine 294 4-[(1-ethylindolyl-4-hexahydropyridinyl)amino]-N-[(2,5-difluorophenyl)methyl ]-1-ethyl-1H·pyrazolo[3,4-b]pyridine_5-formamide 295 4-[(1-ethylindolyl-4·hexahydropyridinyl)amino]ethyl -N_{[3-(trifluorofyl)phenyl]methyl}-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 296 4-[(1-ethenyl-4 -hexahydropyridyl)amino]]iethyl-indole-{[4-(trifluoromethyl)phenyl]methyl}-1 oxime-pyrazolo[3,4_b]pyridine_5-carbamimid 297 4-[(1-Ethyl _4·hexafluoridyl)amino]-N-[(2,6-difluorophenyl)methyl]-1-ethyl-1H-pyrazolo[3 ,4-b]pyridine-5-formamide 298 4-[(1-ethylindolyl-4·hexahydropyridinyl)amino]-N-[(3-phenylphenyl)methyl]-1- Ethyl-1H-pyrido[3,4-b]external b-position-5-formamide 299 4-[(1·ethinyl-4-hexahydropyridinyl)amino]-1-ethyl -N-{[4-(methoxy)phenyl]methylHH-pyrazolo[3,4-b]pyridyl Pyridin-5-carbamamine 87841·96〇3〇3·中. Doc-167- 1283678 300 4_[〇乙醯-4-Pyridine)amino]-1-ethyl-N-[4-(methoxy)phenyl]-1Η_ρ than spit [3, 4-b&gt;Bisodium-5-carbamamine 301 4-[(1-Ethyl-4-pyridinyl)amino]-N-({4-[(dimethylamino))sulfonyl) ]phenyl}methyl)-1-ethyl-lH-p is more than [3,4-b]p than pent-5-cartoamine 302 4-[(1_ethenyl-4-hexahydro) Pyridyl)amino]-1 -ethyl-N-(l,2,3,4-tetrahydro-1-naphthalenyl)_1H-pyrazolo[3,4_b]pyridine-5-carbamimidyl 303 4 -[(1-ethylindolyl-4-hexahydropyridinyl)amino]-N-{[2-(dimethylamino)phenyl]methyl}sodiumethyl-1H-pyrazolo[3,4 -b]pyridine-5-carbamide 304 4-[(1-ethenyl-4-hexahydropyridinyl)amino]-N-[(2,4-dichlorophenyl)methyl]-1 -ethyl to benzo[3,4-b]p ratio-5-y-amine 305 4-[(1-ethylindol-4-hexahydropyridinyl)amino]ethyl-N-[ (2-fluorophenyl)methyl]-1H-pyrazolo[3,4-b]pyridine-5-formamide 306 4-[(1-acetoxy-4-hexahydrop-decyl)amine ]]-N-[(2-Chloro-6-fluorophenyl)methyl]sodiumethyl·1Η·pyrazolo[3,4-b]pyridine-5-carboxamide 307 4·[(1 _ Ethyl 4·hexahydropyridyl)amino]-N-({4- [(Difluoromethyl)oxy]phenyl}methyl)sodiumethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide 308 4-[(1·Ethyl)- 4-hexahydropyridyl)amino]-N-{[3-carbyl·4-(methoxy)phenyl]methyl}-1-ethyl-ΙΗ-ρ is more than [3,4- b]p bis-5-cartoamine 309 4-[(1-ethyl-bromo-4-hexanitro-p-aryl)amino]-N-[(5-alkyl-2·^ ratio decyl group) Methyl]sodiumethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide 310 4-[(1.Acetyl-4-pyridinium p-butyl)amino]- N-(5-Chloro-2,3-dihydro-1H-indol-2-yl)-1-ethyl-1H·pyrazolo[3,4-b]pyridine-5-decylamine 311 4- [(1-Ethyl-4-pyridinyl)amino]ethyl-N-(l,3-oxazol-2-ylmethyl)_1H-pyrazolo[3,4-b] Pyridine-5-formamide 312 4-[(1-ethyl-bromo-4-hexahydrop-decyl)amino]-1·ethyl-N-{[4-(methyl aryl)phenyl ]methyl b 1H·pyrazolo[3,4-b]pyridine-5-formamide 313 4-[indolyl-4-hexahydropyridyl)amino]-N-(2,2- Diphenylethyl)+ethyl-1H-pyrazolo[3,4-b]pyridine_5-formamide 314 4-[(1-Ethyl-4,hexahydro-p-pyryl)amine ]]-1-ethyl_N-({4-[(methyl aryl))]yl}methyl}methyl )-1Η-pyrazolo[3,4-b]pyridine-5-formamide 315 4-[(1-ethyl-bromo-4-hexahydrop-pyryl)amino]-1_ethyl- N_({4-[(Mercurinyl)carbonyl]phenyl}methyl)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 87841_96〇3〇3·中. Doc -168 - 1283678 316 4-[(l-Ethyl-4-pyropyridinyl)amino]-N-{[4-(aminosulfonyl)phenyl]methyl}methylethyl- 1H·pyrazolo[3,4-b]pyridine-5-carbamimid 317 4-[(1-ethylhydrazine) hexahydropyridyl)amino]N-ethyl-N-({3-[( Methylamino)carbonyl]phenyl}methyl)-1Η-pyrazolo[3,4-b]pyridine-5-formamide 318 4-[(1-ethylindolyl-4-hexahydropyridinyl) Amino]-N-{[4-(aminocarbonyl)phenyl]methyl}-1_ethyl-1H-pyrazolo[3,4-b]pyridine_5-formamide 319 4-[ (1-Ethyl-4-pyridyl p-pyrifosyl)amino]-1·ethyl-indole-{[6·(methoxy)·3-pyridyl]methyl}-1Η-pyrazole And [3,4-b]pyridine-5-formamide 320 1-ethyl-N-4-hexahydropyridyl-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η- Pyrazolo[3,4-b]pyridine-5-formamide 321 1-ethyl-N-(4-hexahydropyridylmethyl)-(tetrahydro-2H-piperidinylamino)- 1Η-pyrazolo[3,4-b]pyridine-5-carbamimid 322 1-ethyl-indole-[1-(ethyl distillyl)-4-ττ chloride p ratio benzyl]-4- (tetrazol-2H-methylene-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carbamimid 323 1-ethyl-N-{1_[(1-A Base ethyl) continuation base]_4-hole nitrogen p ratio }}-4-(tetrahydro-2H-piperazin-4-ylamino)-1Η-pyrazolo[3,4_b]pyridine-5·carbamimid 324 succinyl acid)-4-ττ Chlorine p ratio benzyl]-1-ethyl-4-(tetraqi-2H-piperidinylamino)-1 Η-pyrazolo[3,4-b]pyridine-5-carbamimid 325 ethyl -Ν_[1·(())-4-ττ nitrogen ρ ratio decyl]-4-(tetrachloro-2H-p-endan-4-ylamino)-1Η-pyrazolo[3,4 -b]pyridine-5-carbamamine 326 1-ethyl-N-{1-[(phenylmethyl)sulfonyl]-4-hexahydropyridinyl}-4-(tetrahydro-2H-piperidin Cyclopropylamino)_1H-pyrazolo[3,4-b]pyridine-5-carboxamide 327 1-ethyl-indole-[1·(benzoic)-4-ττ nitrogen outer b-precipitate 4-(4-gas-2H-pyran-4-ylamino)·1Η-pyrazolo[3,4-b]pyridine-5-carbamimid 328 1_ethyl-N-[l -(propyl continuation)-4-ττ chlorop ratio butyl]-4-(tetrazine-2H-cyclopentanylamino)-1Η-pyrazolo[3,4-b]pyridine_ 5_Mercaptoamine 329 N-[l-(Lactinyl)-4-hexanitro-b-butyl]-1-ethyl-4-(tetrazine-2H-P guolate-4-ylamine ))-Η-pyrazolo[3,4-b]pyridine_5·carbamamine 330 1-ethyl-indole-[1·(3-咬基基基基)-4-azepine yttrium -4-(tetrazol-2Η-^ -4--4-ylamino)_1 ·ρ ratio vomit [3,4-b]external b-precipitate-5-cartoamine 331 N-[l-(3,3-dimethylbutylidene)-4-hexahydropyridyl]-1-ethyl -4-(tetrahydro-2H-piperidinylamino)-1Η-pyrazolo[3,4_b]pyridine-5-carbamamine 87841·96〇3〇3_ Doc -169- 1283678 332 1-Ethyl-N-[l-(2-ethylbutylidene)-4-hexanitrogen p-butyl]-4·(tetrachloro-2H-^-an-4-ylamine比比吐和[3,4-b]p比淀_5_甲甲胺333 N-[l-(cyclopentylacetate chloride p than decyl) small ethyl _4-(tetrahydro-2H_ brig喃-4-ylamino group than oleno[3,4-b]p than yt-5-ylamine 334 1-ethyl-N-[l-(2-methylpropionate)-4-hexa Chlorophyllin b benzyl]-4-(tetrachloro-2H-fluorenyl-4'ylamino)-1Η_ρ比峻[3,4-b]p ratio -5-5_甲甲胺335 1-ethyl -4·(Four gas-2H_ shout-4-ylamino)-indole-[1_(tetrachloro-2H-P-pyranyl-4-ylcarbonyl)-4·hexahydropyridyl]_1H-pyrazole [3,4-b]pyridine-5-formamide 336 1-ethyl·Ν·(1-propanyl-4-TT nitrogen external b-position) 4-(tetrachloro-2H-p-butyl- 4-aminoamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 337 N-[1-(N-acetoxyglycine)·4-hexachloropyp 1-ethyl 4-(tetrahydro-2-pyrano-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-formamide 338 1-ethyl -N-[l-(4-?-fu-p- phenylacetate)-4-hexachloro-p-butyl]-4-(tetrahydro-211-0-decano-4-ylamino) than spit[3 ,4-b]p, butyl-5-formic acid amine 339 1-ethyl-indole-{1-[(4-keto) Hexyl)carbonyl]-4-hexafluoropyridinyl}-4-(tetrazine-2H-bucky-4-ylamino group is more than [3,4-b]p than lake-5-formate 340 1- Ethyl-N-[l-(l-hexahydropyridinyl)-4-hexahydropyridinyl]-4-(tetrazo 2 Η 略 喃 -4-ylamino) is more than [3, 4-b]p butyl-5-cartoamine 341 1-ethyl-N-{1_[(1-methyl-5. keto-3-tetrahydropyrrolyl)carbonyl] }}-4-(tetrachloro-2H-fluoren-4-ylamino)-1Η-ρ is more than [3,4-b]p than pyridine-5-carbamid 342 1-ethyl-fluorene {1-[(3-Methyl-3-epoxypropenyl)carbonyl]-4-hexahydropyridinyl 7-yl}-4-(tetrahydro-2-indole-piperidin-4-ylamino)-1Η_ Pyrazolo-; 3,4-b]pyridine j-carbamamine 343 1-ethyl-indole-{1-[(4-(phenyl)ethenyl]-4-hexahydro outside b-bityl}- 4-(tetraoxane 2H·piperidin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carbamimid 344 Ν-{[1-(3,3-di Methylbutylidene)-4-hexahydrop-pyrifosyl]methyl}-1_ethyl 7 (tetrahydro-2H-fluoren-4-ylamino)-1H-p is more than [3,4- b]p butyl-5-cartoamine 345 Ν-{[1-(cyclopentylethyl fluorenyl)-4-hexahydropyridyl]methyl}-1-ethyl-4-(^ hydride-2H&gt ; Chenan-4-ylamine ratio also [3,4-b> butyl--5-carbamamine 346 Ν-{[1-(Cyclopropylcarbonyl)-4-hexahydropyridyl]methyl}sodiumethyl-4-(tetra$2H_pyran-4-ylamino)_1H-pyrazolo[ 3,4-b]pyridine-5-methamine amine 87841-960303•中. Doc -170- 1283678 347 1-ethyl·Ν-({1-[(4-ketocyclohexyl)carbonyl]-4-hexahydropyridinyl}methyl)-4·(tetrachloro·2Η-jum -4-ylamino-aminopyrazine[3,4-b]p is more than _5•cartoamine 348 1-ethyl-indole-({1-[(4-fluorophenyl)ethenyl]- 4-Hexidopyridinyl}methyl)-4-(tetrahydro-2H-pyran-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 349 1 -ethyl·Ν-({1-[(1-methyliso)_3_tetrazine p-l-yl)-based group]_4·ττ-rat pyridyl}methyl)-4-(tetrahydro-2Η- Piperazin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 350 methyl 3_[(1_ethyl-5-{[(phenylmethyl)) Amino]carbonyl}_1Η·pyrazolo[3,4-b]pyridin-4-yl)amino]cyclohexanecarboxylate 351 3-[(1-ethyl-5-{[(phenyl) Amino]carbonyl]_1H_pyrazolo[3,4-b]pyridinyl)amino]cyclohexanecarboxylic acid 352 1-ethyl-N-(phenylmethyl)-4-(4 - hexahydropyridylamino)-1 Η-pyrazolo[3,4-b]external b--5-cartoamine 353 1_ethyl-4-({l-[(methoxy)ethetidine) Ethyl]-4-hexahydrop-pyrifosyl}amino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxylate ethyl ester 354 1-(1-methylethyl)-4_( Tetrahydro- 2Η_^--4-yl Base)-1Ηπ 唆[3,4-b]pyridine-5-carboxylic acid ethyl ester 355 4-(cyclohexylamino)ethylidene-N-methyl-1H-pyrazolo[3,4- b] Pyridin-5-formamide 356 1-ethyl-N-(4-fluorophenyl)-6-methyl-4-(tetrahydro-2H-piperidin-4-ylamino)· 1H_p ratio并[3,4-b]p than yt-5-carbamide 357 1-ethyl-6-methyl_N-{[4-(methylsulfonyl)phenyl]methyl}-4- (tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-formamide 358 N-(2,3-dihydro-1H- though 2_yl)_1_ethyl-6-methyl-4-(tetrahydro-2H·jol-4-ylamino)-1Η-峨峻和[3,4_b] 外乙淀-5_甲醯Amine 360 1-ethyl-N-[3-(l-hexahydrop-decylcarbonyl)phenyl]-4-(tetrahydro-2H-p-guanosyl-4-ylamino)-1Η-pyrazolo[3 ,4-b]pyridine-5-carbamimid 361 1-ethyl·indole-[4-(1methylethyl)phenyl]_4·(tetrahydro-2-indol-4-ylamino)-1Η -External b and [3,4-b]external b-precipitate-5-cartoamine 362 1-ethyl-indole (2-fluorophenyl)-4-(tetrahydro-2H- shouting-4_ The amino group)·ιη_ρ ratio is also [3,4-b]p than the lake-5-cartoamine 87841-960303-中. Doc -171- 1283678 363 N-{3-[(Dimethylamino)carbonyl]phenyl}-l-ethyl-4_(tetrahydro-2Η· 喃 -4--4-ylamino)-1Η-ρ ratio Spit and [3,4-b> butyl-5-carbamamine 364 Ν-{4-[(difluoromethyl)oxy]phenyl}-1_ethyl ice (tetrahydro-2 Η- brim 4--4-aminoamino)_1Η·pyrazolo[3,4-b]pyridine-5-carboxamide 365 N-{4-[ethylidene(methyl)amino]phenyl}-1_B 4-(tetrahydro-2H-pyran-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 366 1-ethyl-N-(4- Phenyl)-4-(tetrahydro-2H-pyran-4-ylamino)-1Η-ρ than ton[3,4-b]pyridine-5-carboxamide 367 1-ethyl_N -[4_(4-moffinyl)-2_(trifluoromethyl)phenyl]_φ·(tetrahydro-2H_p-decyl-4-ylamino)_1H-p is more than [3,4- b]p than yt-5-cartoamine 368 1-ethyl-N-4-p than decyl-4-(tetrahydro-2H-pyran-4-ylamino)-1Η-external b [3,4-b]pyridine-5-formamide 369 1-ethyl_N_{4-[(4-methyl-1-hexahydro-exo bp) carbonyl]phenyl}-4-(four Hydrogen-2H-Bucer-4-ylamino)-1Η-峨君[3,4-b]p than yt-5-carbamide 370 1-ethyl-N-[2_(2-keto -1-tetrahydro? ratio p) phenyl]_4-(tetrahydro-2H_bromo-4-ylamine )-1Η-^ ratio is also [3,4-b]p than dian-5-anthracene amine 371 1-ethyl-N_[3-(methyl-branched)phenyl]_4-(tetrahydro-2H - 喃 -4- 基 基 ) ) -1 -1 -1 -1 [ [ 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 淀 { { { { { { { { { { { }}-1_ethyl_4-(tetrahydro-2Η·ϊ派喃-4-ylamino group is more than [3,4-bp than yt-5-carbamide 373 1-ethyl-N- {3-[(methyl acid)amino]phenyl}_4·(tetrahydro-2H-pyran-4-ylamino group than spit[3,4_b]p than lake-5-formamide 374 1 -ethyl-Ν·(4-fluoro-2-# is phenyl)-4-(tetrahydro-2H-fluoren-4-ylamino)-1Η·β than tons of [3,4-b Exo b-precipitate-5-methylamine 375 N-(4-chlorophenyl)_1·ethyl-4-(tetrahydro-2H- sher-4-ylamino group than ton[3,4-b Pyridine-5-formamide 376 N-(3-chloro-2-cyanophenyl)succinyl-4-(tetrahydro-2H_^anyl-4-ylamino)-1Η-ρ ratio spit And [3,4_b&gt;Bisho-5-formic acid amine 377 1·ethyl-Ν-[3-(1·hexahydro outside b) phenyl] 4-(tetrahydro-2H-brum喃-4-ylamino)-1Η-ρ than oleno[3,4-b]p ratio ··5·甲含胺379 1-ethyl-Ν_[2·(methyl acid) phenyl] -4-(tetrahydro-2Η- sher-4-ylamino)_ | IH-p ratio bite [3, 4_b]p than the lake -5 - brewing amine 8784l-960303-zhong. Doc -172- 380 N-{2-[Ethyl(methyl)amino]phenyl}sodiumethyl-4-(tetrahydro-211-piperidin-4-ylamino)_1H-pyrazole [3,4-b]pyridine-5-formamide 381 1-ethyl_N-[3-(4-?-fusinyl)-phenyl]_4-(tetrazine-2H4-c-butyl-4 -ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carbamimid 382 N_(4-chloro-3-chlorophenyl)-1_ethyl-4-(four Nitrogen-2H-pyran-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 383 1-ethyl-N-(3-hydroxyphenyl)-4- (tetrahydro-2H-piperazin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 384 N-(3-chlorophenyl)succinyl-4 -(tetrahydro-2H-piperazin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 386 Ν-[3·[(acetamido) A 4-(methoxy)phenyl]-1-ethyl winter (tetrahydro-2H-piperidinylamino)_1Η·pyrazolo[3,4-b]pyridine-5-formamidine Amine 387 1_ethyl-N-[4-(l-hexahydropyridylsulfonyl)phenyl]-4·(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazole [3,4-b]pyridine-5-carbamimid 388 N-(3-{[cyclohexyl(methyl)amino]carbonyl}phenyl)succinyl 4-(tetrahydro-2H- britant- 4-aminoamino)-1Η-pyrazolo[3,4-b]pyridin Acridine_5_formamide 389 1·ethyl-N-[2-(4•morpholinyl)phenyl]-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η- Pyrazolo[3,4-b]pyridine-5-formamide 390 N_{3-[(acetamido)sulfonyl]phenyl}-1·ethyl-4-(tetrahydro-2Η- Piperazin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carbamimid 391 N-(3-chloro- 4-phenyl)-1-ethyl_ 4-(four gas-2H· shouting-4_ylamino)-1H-pyrazolo[3,4_b]pyridine-5-carbamimid 392 1-ethyl-Ν·{4-[(methane) Mercapto)amino]phenyl}ice (tetrahydro-2H-piperidin-4-ylamine)[3,4-b]externate-5-cartoamine 393 1-ethyl-N- {3-[(Methylamino)carbonyl]phenyl}-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η_pyva[3,4-b]pyridine-5-A Indoleamine 394 1-ethyl-4-(tetrahydro-2H-bran-4-ylamino)-N-[3-(trifluoromethyl)phenyl]-1H-pyrazolo[3,4 VII] Pyridin-5-formamide 395 1-ethyl-Ν·3-ρ ratio decyl-4-(tetrazol-2H-pyran-4-ylamino group than spit[3,4-b] Pyridine-5-formamide 396 N-(3,4-diphenyl)-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1Η-pyrazolo[ 3,4-b]pyridine-5-decylamine 87841-9603〇3_. Doc -173- 1283678 397 Ν·[3-(Aminothiol)-4-chlorophenyl]-1_ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1Η -pyridinium[3,4-b>pyramid-5-carbamamine 398 1-ethyl-N-[3-(4-?-fusyl)phenyl]_4-(tetrahydro-2H- shout喃冰基胺基比峻和[3,4七&gt; 比淀_5_Mercaptoamine 399 1-ethyl-N_[4_(4_?), 驴 基 ) )) phenyl]_4- (four Hydrogen 2H_t-Pan-4-ylamino group is more than [3,4_b]p than yt-5-carbamamine 400 1-ethyl-anthracene {2-[(4-methyl hexahydropyridinolate) ))carbonyl]phenyl bromide 4_(tetrahydro-2Η-Ϊ派喃-4-ylamino)·1Η·ρ than spit[3,4-b]p than _5_甲醯 401 [( Dimethylamino)carbonyl]phenyl}sodiumethyl-4-(tetrahydro-2H-isan-4-ylamino)-1Η«^ than ton[3,4-b]p than pent-5- Methionine 402 N-[2-chloro-4-(trifluoromethyl)phenyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1Η-ρ比峻和[3,4-b&gt; 比丁-5-Metformamide 403 N-{2-[(ethylamino)methyl]phenyl} small ethyl bucket (tetrahydro-2 Amino group)-1Η-ρ ratio 唆[3,4-b]external b bit-5-carbamamine 404 N-(2-phenylphenyl)-1-ethyl-4-(tetrahydro-2H -Pantan-4-ylamino)-1Η·ρ ratio And [3,4-b]pyridine-5-formamide 405 N-(3-chloro-2-fluorophenyl)-1-ethyl-4-(tetrahydro-2H-pyran-4-yl Amino)-1Η-pyrazolo[3,4-b]pyridine-5-formamide 406 1-ethyl-N-(3_phenylene)-4-(tetrahydro-2H- shouting 4_ylamino)-ιη·external b and [3,4-b]pyridine-5-formamide 407 N-(2-cyano-3-fluorophenyl)-1-ethyl-4- (tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridine-5-formamide 408 1-ethyl-N_[4_(propyl fluorenyl) Phenyl] ice (tetrahydroanthracene-throm-4-ylamino group 唆[3,4-b]externate ti 5·carbamamine 409 Ν-{4-[(dimethylamino) Carbonyl]phenyl}_1_ethyl ice (tetrahydro-2fj_pyranylamino)_1Η-pyrazolo[3,4-b]pyridine-5-methalamine 411 1_ethyl-N -[4·(甲 continued 醢)phenyl]_4_(tetrahydro-2Η_ι派喃_4_ylamino)_ 1H-pyrazolo[3,4_b]pyridine-5-formamide 413 N-{ 4-[(Ethylamino)methyl]yl}}1-ethyl_4_(tetrazepin-4-ylamino)-1Η-ρ ratio+[3,4-b]p ratio -5-Artemisamine 414 1-ethyl-4-(tetrahydro-2H-bungan-3-ylamino) than succinyl [3,4-b]p than yt-5-carbamamine 87841-96 〇3〇3·中. Doc -174- 1283678 415 N-[2-(Aminosulfonyl)ethyl]_4_(cyclohexylamino)-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5- Methionamine 416 N-(2-Amino-2-ketoethyl)-4·(cyclohexylamino)ethylidene-1H-pyrazolo[3,4-b]pyridine-5-formamidine Amine (non-preferred name) 417 4-(cyclohexylamino)-1-ethyl-N-{2-[(methylsulfonyl)amino]ethyl}-1Η-pyrazolo[3,4 -b]pyridine-5-methanamine 418 4-(cyclohexylamino)-1-ethyl(tetrahydro-2H-pyran-4-yl)_1H-pyrazolo[;3,4-b]峨丁-5-Metamine 419 4_(cyclohexylamino)_1_ethyl-N-[(l-methyl-1H-pyrazol-4-yl)methyl]-1H-leaf sputum and [ 3,4-b]indole-5-formamide 420 4-(cyclohexylamino)_1_ethyl-N-{[3-(methylsulfonyl)phenyl]methyl}-1Η_pyridyl Also [3,4-b]exo b far-5-carbamide 421 N-{[3-(aminocarbonyl)phenyl]methyl b 4_(cyclohexylamino)-1-ethyl-1H -pyrido[3,4-b> than bite-5-formamide 422 4-(cyclohexylamino)_1-ethyl-N-(tetrahydro-2-furanylmethyl)-1Η-pyridyl Azolo[3,4-b]p ratio ·5-cartoamine 423 4-(cyclohexylamino)-indole-({4-[(dimethylamino)sulfonyl]phenyl}methyl )-1-ethyl-1H-pyrazolo[3,4 -b]pyridine-5-methanamine 424 N-[(5-chloro-2-pyridyl)methyl]-4·(cyclohexylamino)-1-ethyl-1H-pyrazolo[3 ,4-b]pyridine-5-formamide 425 4-(cyclohexylamino)-1-ethyl-N-{[4-(methylsulfonyl)phenyl]methyl}·1Η-pyridyl And [3,4-b]external b-position-5-formamide 426 4-(cyclohexylamino)-1-ethyl-N_{[6-(methoxy)_3_pyridyl]methyl} -1Η-外匕 匕和[3,4-b&gt; 比淀-5-Methylamine 427 4-(cyclohexylamino)ethylidene·Ν-{4-[(methylamino)carbonyl]phenyl }-1Η-pyrazolo[3,4-b]pyridine-5-formamide 428 4_(cyclohexylamino)-1-ethyl·indole-({3-[(methylamino)carbonyl)benzene }}methyl)-1Η-pyrazolo[3,4-b]pyridine-5-carbamimid 429 Ν-{[4-(aminocarbonyl)phenyl]methyl}-4-(cyclohexylamine 1-ethyl-1-indole-pyrazolo[3,4-b]pyridine-5-methamine 430 4-(cyclohexylamino)-1-ethyl-N-[(4-hydroxybenzene) Methyl]-1H-pyrazolo[3,4-7]pyridine-5-carboxamide 87841-9603〇3_ Doc -175- 1283678 431 4-(cyclohexylamino)-1-ethyl-N-{[4-(methoxy)phenyl]methyl b ih_pyrazolo[3,4-b]pyridine -5-Protonamine 432 4-(cyclohexylamino)-N-[(3,4-difluorophenyl)methyl H-ethyl-1H-pyrazolo[3,4-b]pyridine- 5-Proline 433 4-(cyclohexylamino)ethylidene-N-{[4-(trifluoromethyl)phenyl]methyl b 1H_pyrido[3,4-b]p ratio -5-5-formic acid amine 434 4-(cyclohexylamino)ethylidene-N-({3-[(methylsulfonyl)amino]phenyl}methyl)_ 1H·pyrazolo[3, 4_b]pyridine-5-methanamine 435 4-(cyclohexylamino)-N-[(2,5-difluorophenyl)methyl]-1-ethyl-1H-external b s[3, 4-b]pyridine-5-formamide 436 4-(cyclohexylamino)-1·ethyl-N_[(4-methylphenyl)methyl]-iH_external b[3,4 -b] pyridin-5-formamide 438 4-(cyclohexylamino)ethylidene-N-(2_{4-[(methylsulfonyl)amino]phenyl}ethyl)-1Η- Pyrazolo[3,4-b]pyridine-5-formamide 439 4-(cyclohexylamino)·1·ethyl-N-[(2-stupyl)methyl]-iH-p ratio并[3,4-b] 匕 匕-5-formic acid amine 440 4-(lorylhexylamino)-N_[(3,4-monolacyl)methyl]-1-ethyl-1H- P ratio also [3,4-b] bamboo 1: lake-5-carbamide 4 41 4-(Cyclohexylamino)-N-[(3,5-dichlorophenyl)methyl]-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-formamidine Amine 442 4-(cyclohexylamino)-1-ethyl-N-(2-phenylethyl than benzo[3,4-b]external oxime-5-formamide 443 4-(cyclohexane Amino)-1·ethyl_N_(1,2,3,4-tetrahydrofuranylpyrazine[3,4-b]p ratio read;-5-formamide 444 4-(cyclohexyl) Amino) small ethyl-N-{[2-(methyl sulfenyl)phenyl]methyl bromide-external!: succinyl[3,4-b]external b-precipitate-5-carboxamide 445 4-(cyclohexylamino)ethylidene-N-[2_(4-phenylphenyl)ethyl] is more than [3,4_b], and t is -5-carbamamine 446 N]2- [4-(Aminosulfonyl)phenyl]ethyl}_4-(cyclohexylamino)-1-ethyl" 1H-pyrazolo[3,4-b]pyridine-5-carboxamide 447 4-(cyclohexylamino)ethylidene-N-({2-[(methylamino)carbonyl)phenyl}methyl)_1H_ ρ than spit[3,4-b]p than pent-5-A Amine amine 87841-960303-zhong. Doc •176- 1283678 448 4-(cyclohexylamino)-1-ethyl-N-{[2_(methylsulfonyl)phenyl]methylid iH-exocarbazolo[3,4-b] Pyridine-5-formamide 449 2-[({[4-(cyclohexylamino)-1ethyl_1H_p is more than [3,4-b]p than _5_yl]) Methyl]methyl]benzoate 450 4-(cyclohexylamino)-1·ethyl-oxime {2-[4-(methyl-decyl)phenyl]ethylpyrazolo[3,4 -b]pyridine-5-methanamine 451 N-[4,5-bis(methoxy)-2,3-dihydro-1H·indol-2-yl]_4-(cyclohexylamino) small B -1-1H-P is more than [3,4-b], and it is 452 4-(cyclohexylamino)ethylidene-N_{[2_fluoro-3-(trifluoromethyl) Phenyl]methyl is more than [3,4-b>pyramid-5-formic acid amine 453 4-(cyclohexylamino)·Ν-[(3,4-dimethylphenyl)methyl] Ethyl-1H-pyrazolo[3,4-b]external b-bend-5_cartoamine 454 4-(cyclohexylamino)-1-ethyl-indole-[2·(4-fluorophenyl) Ethyl]-1H-pyrazolo[3,4-b]pyridine-5-formamide 455 4-(cyclohexylamino)-1-ethyl-N-[2-(4-methylbenzene Ethyl)ethyl]_1H-pyrazolo[3,4-b]p than yt-5-anthracene amine 456 4·(cyclohexylamino)-1-ethyl-N-{2-[4-( Methoxy)phenyl]ethyl}-1Η-pyrazolo[3,4-b]pyridyl Pyridin-5-formamide 457 4-(cyclohexylamino)ethylidene-N-(2-pyridylmethyl)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide III Fluoroacetate 458 4-(cyclohexylamino)-N-[(3,5-difluorophenyl)methyl]sodiumethyl-1H-pyrazolo[3,4-b]pyridine-5- Indoleamine 459 4-(cyclohexylamino)-N-(2,3-dihydro-1H-indol-1-yl)sodiumethyl-1H-pyrazolo[3,4-b]pyridine-5- Indoleamine 460 4-(cyclohexylamino)_N-{[4-(didecylamino)phenyl]methyl}sodiumethyl-1H-pyrazolo[3,4-b]pyridine_5_ Methionine trifluoroacetate 461 4-(cyclohexylamino)-1-ethyl-N-[(2-fluorophenyl)methyl]-1Η·pyrazolo[3,4-b] :Bite-5-carbamide 462 N-{[2,4-bis(methoxy)phenyl]methyl b 4-(cyclohexylamino)-1-ethyl-1H-pyrazolo[3 , 4-b]pyridine_5_formamide 463 N-[(6-chloro-2-pyridyl)methyl]_4-(cyclohexylamino)-1-ethyl-1H-pyrazolo[ 3,4-b&gt;bipyridin-5-carbamide trifluoroacetate 87481-960303·中. Doc -177- 1283678 464 [Ethyl (meth)amino]phenyl}methyl)-4-(cyclohexylaminoethyl-1H·leafb[3,4-b]p -5-formic acid amine trifluoroacetic acid 465 4-(cyclohexylamino)-1-ethyl_Ν_{[4·fluoro-3-(trifluoromethyl)phenyl]methyl}-1Η_ρ ratio spit And [3,4-b]峨丁-5-methamine 466 4-(cyclohexylamino)-N-[(lR)-2,3-dihydro-1H_茚-1_yl H•B Base_1H-pyrazolo[3,4-b]pyridine-5-formamide 467 4_(cyclohexylamino)-N-[(2,6-dichlorophenyl)methyl]-1-B Base _ih_p bilis[3,4-b]pyridine-5-methanamine 468 3_[({[4-(cyclohexylamino)-1-ethyl-1H-P ratio vomit [3,4_b ] p 淀 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _1_ethyl-iH-p ratio 峻[[3,4-b&gt; pyridine-5-carbamide 470 4·[({[4_(cyclohexylamino)-1-ethyl-1H-P)峻 并 [3,4-b]p than yt-5-yl]-Wenyl}amino)methyl]benzoic acid methyl ester 471 4-(J succinylamino)-1·ethyl-N-( 1H-tetrakis-5-ylmethyl)-1Η-ρ ratio 并[[3,4-b&gt; butyl--5-carbamide 472 4-(cyclohexylamino)-N-({4- [(Difluoromethyl)oxy]phenyl}methyl) small keto-1H-pyrido[3,4-b]pyridine-5-formamide 473 4-(diacylamino)_1_ethyl-N-[(2-methyl·1,3·ρ plug Also -4·yl)methyl]-1H_pyrazolo[3,4-b]pyridine-5-formamide 474 N-[(2-chloro-6-fluorophenyl)methyl]-4- (cyclohexylamino)-1•ethyl-1H-pyrazolo[3,4-b]pyridine-5-formamide 475 N-{[2-(aminocarbonyl)phenyl]methyl}· 4-(cyclohexylamino)ethylidene-1H-pyrazolo[3,4-b]pyridine-5-carboxamide 477 4-(cyclohexylamino)-N-{[2-(dimethyl Amino)phenyl]methyl}-1-ethyl_1H-pyrido[3,4-b]p than lake-5-cartoamine 478 4-(cyclohexylamino)-1-ethyl -N-[(4-fluorophenyl)methyl]-1Η-pyrazolo[3,4-7]pyridine-5-carboxamide 479 4-(anilinoyl)-1-ethyl-N- {[3-(Trimethyl)yl]methyl is more than [3,4-b&gt; than 矣-5-carbamide 480 4-(cyclohexylamino)-N-[(2,6) -Difluorophenyl)methyl H-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide 87841-960303-中. Doc -178- 1283678 481 4-(cyclohexylamino)ethylidene-N-[(3-fluorophenyl)methyl]-1 oxime-pyrazolo[3,4-b]pyridin-5-carboxamidine Amine 482 4-(cyclohexylamino)ethylidene-N-{[2-(trifluoromethyl)phenyl]methyl}-1 fluorene-r-oxazolo[3,4-b]pyridine-5-- Indoleamine 483 N-(5-Chloro-2,3-dihydro-1H-indol-2-yl)-4-(cyclohexylamino)ethylidene·1Η-ρ ratio Jun [3,4- b]p-precipitate-5-formamide 484 4-(cyclohexylamino)ethylidene-N-({4_[(methylamino)carbonyl]phenyl}methyl)-1Η- [3,4-b]external b-position-5-formamide 485 4-(cyclohexylamino)ethylidene-N-[4-(methoxy)phenyl]-1Η-pyrazolo[3 ,4-b]pyridine-5-methanamine 486 4-(cyclohexylamino)-1-ethyl-N-[(6-indolyl-1,6-dichloro-3-p ratio decyl) )methyl]-1H-pyrazolo[3,4_b]pyridine-5-formamide 487 4-(cyclohexylamino)-1·ethyl-oxime·(3_pyridylmethyl)·1Η_ Pyrazolo[3,4-b]pyridin-5-formamide 488 4-[({[4-(cyclohexylamino)-1·ethyl-1H-pyrazolo[3,4-b] Pyridyl-5-yl]carbonyl}amino)methyl]benzoic acid 489 3_[({[4-(cyclohexylamino))ethyl)1Η_pyrazolo[3,4-b]pyridine-5- Carbonyl}amino)methyl]benzoic acid 49 0 4-(lorylhexylamino)_N-(2,3_diaza_1H-indol-2-yl)-1-ethyl-1Η_ρ ratio '^ and [3,4-b]p than the lake-5 -formic acid amine hydrochloride 491 4-(cyclohexylamino)-N-(2,3-dihydro-1H-indol-2-yl)sodiumethyl-1H-pyrazolo[3,4-b] Pyridine-5-formamide methanesulfonate 492 Ν-({2-[(1,1·dimethylethyl)oxy]-3-pyridyl}methyl)small ethyl_4_ (tetrahydro) -2Η-piperidinylamino)-1Η-pyrazolo[3,4_b]pyridine-5-carbamidamine trifluoroacetate 493 N-[(3-carbyl-4-methylphenyl)- A small ethyl benzene (tetrahydro-2H·pyran-4 ylamino)-1 Η-pyrazolo[3,4-b]pyridine-5-carboxamide 494 N_[(4-carbyl- 2-methylphenyl)methyl]-1-ethyl-4·(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5- Methionine 495 N-({2-[(difluoromethyl)oxy)phenyl}methyl)methylethyl 4-(tetrahydro-2H-piperidin-4-ylamino)-1Η- Pyrazolo[3,4_b]pyridine-5-carboxamide 87841·96〇3〇3·中. Doc -179- 1283678 496 1-Ethyl-indole_({2·[(1-methylethyl)oxy)phenyl}methyl)_4_(tetrahydro·2Η_ 喃尔-4_ylamino)· 1Η-External b is also [3,4-7] butylate-5-formic acid amine 497 1-ethyl_N_({3-[(1-methylethyl)oxy)phenyl}methyl)_4_ (tetrahydro-2h_ bhak-4-ylamino group is more than 唆[3,4_b]p than _5_carbamamine 498 N-({3_[(di-methyl)oxy)phenyl} Base) small ethyl _4·(tetrahydro-2H-T-pyran-4-ylamino group than spit[3,4_b]p than _5_cartoamine 499 1_ethyl-N_{[4 ·#Pretyl-3-(methoxy)phenyl]methyl}_4_(tetrahydro-2H-bran-4-ylamino group is more than [3,4-b]p than _5_carboxylic acid Amine 500 N-[(5-Ethyl-2-hydroxyphenyl)methyl]sodiumethyl-4·(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3 ,4-b]pyridine-5-formamide 501 1-ethyl-4-(tetrahydro-2H-bran-4-ylamino)_Ν·{2·[3_(trifluoromethyl)phenyl Ethyl thiophene [3,4-b]p is more than 5-aminoamine 502 N-{[4_(ethinyl)phenyl]methyl}_1_ethyl_4-(tetrachloro -2H- brim-4-ylamino)_1H_pyrazolo[3,4-b]pyridine-5-carboxamide 503 1_ethyl-N-[2-(3- phenyl)ethyl ]-4-(tetrahydro-2H-^exan-4-yl) Amino)_1H-pyrazolo[3,4-b]pyridine-5-carboxamide 504 N-[2-(3-chlorophenyl)ethyl]-1-ethyl-4-(tetrahydrogen) -2H-misan-4-ylamino)_1H-pyrazolo[3,4-b]pyridine·5-formamide 505 1-ethyl-4-(tetrahydro-2Η-17-decane- 4-ylamino)-indole-(2-{4-[(trifluoromethyl)oxy]phenyl}ethyl)-1Η-pyrazolo[3,4-b]pyridine-5-formamidine Amine 506 1-ethyl-N-{2-[3-(methoxy)phenyl]ethyl}-4-(tetrahydro-2H·piperidin-4-ylamino)-1Η-pyrazole [3,4-b]pyridine-5-formamide 507 N-[2-(4-ethylhydrazinophenyl)ethyl]-1-ethyl-4-(tetrahydro-2H- shouting-4 -ylamino)_1H_pyrazolo[3,4_b]pyridine-5.carbamamine 508 N-[2-(3,4-dichlorophenyl)ethyl]sodiumethyl-4-(tetrahydro) -2H_pipelanylamino)-1Η-pyrazolo[3,4-b]pyridine-5-formamide 509 N-{2-[3-(aminosulfonyl)phenyl]B Keb 1-ethyl-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-formamide 510 N-{2- [3,4-bis(methoxy)phenyl]ethyl}ethylethyl-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b Pyridine-5·carbamamine 512 N-[2-(2,3-dichlorophenyl)ethyl]sodiumethyl-4-(tetrahydrogen) -2H-piperazin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine_5-formamide 87841-96〇3〇3-中. Doc -180 - 1283678 513 N-{2-[3,5-bis(methoxy)phenyl]ethyl}_1-ethyl·4_(tetrahydro-2-indole-piperidin-4-ylamino)- 1Η-ρ比峻和[3,4-b]p 比淀-5-甲甲胺514 514 1-ethyl-N-{2-[3-methyl-ice (methoxy)phenyl]ethyl} Ice (tetrahydro-2H-piperazin-4-ylamino)_1H-pyrazolo[3,4-b]pyridine-5-carboxamide 515 N· [2-(2,6-. Esteryl)ethyl]·1_ethyl-4-(tetrazine-2H-bran-4-ylamino)-1Η_ρ than bite [3,4-b]p than pent-5-formamidine Amine 516 N-{2_p,6-bis(methoxy)phenyl]ethyl}-1_ethyl_4_(tetrahydro-2H-pyran-4-ylamino)-1Η·pyrazolo[ 3,4-b]pyridine-5-formamide 517 1-ethyl-N-[2_(2-methylphenyl)ethyl]-4-(tetrahydroendan-4-ylamino)- 1H-p is more than 唆[3,4-7&gt; bis--5-carbamide 518 Ν-[(3,4-dimethylphenyl)methyl]sodiumethyl-4-(tetrahydro-2-indole) - 喃 -4--4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carbamimid 519 N-[4,5-bis(methyllacyl)_2,3_two mice -1H-indol-2-yl]·1_ethyl-4-(tetrachloro-2H_pyran-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 521 N-{2-[4-(Aminothiol)phenyl]ethyl}·1_ethyl-4-(tetrahydro-2H-bran-4-ylamino)·1Η_ρ ratio [3,4-b]p ratio -5-5-formamide 522 1_ethyl_N-{[2-(methylsulfinyl)phenyl]methyl}_4-(tetrahydro-2H_ Piperid-4-ylamino)·1Η-pyrazolo[3,4-b]pyridine-5-carbamimid 523 1-ethyl-N-(2-phenylethyl)-4-(four Hydrogen-2H- shouting-4_ylaminobispyrazolo[3,4-b]pyridine-5-formamidine 524 N-{[4-(Dimethylamino)phenyl]methyl}methylethyl (tetrahydro-2H-pyran-4-ylamino) than spit[3,4-b> butyl- 5-Mercaptoamine 525 1_ethyl-N-[2_(4-fluorophenyl)ethyl]-4-(tetrahydro-2Η4-an-4-ylamino)-1Η·pyrazolo[3, 4-b]pyridine-5-carbamimid 526 1-ethyl-indole-[2·(4-methylphenyl)ethyl]-4-(tetrahydro-2H-pyranyl-4-ylamino )·1Η_外1: spit[3,4-b]externate b--5-carbamamine 527 N-{[3-(amino sulfhydryl)phenyl]methyl}methylene-4 -(tetrahydro-2-indole-scarred-4-ylamino)-1Η-ρ is more than [3,4-b]p than ammonium 5-carboxylate 528 1·ethyl-N-[(4 -methylphenyl)methyl]-4-(tetrahydro-2H-chloropyran-4-ylamino)-1H_p is more than [3,4-b]p than 嗓·5-formamide 530 1 ·ethyl_Ν-{[4·glycol_3_(trifluoromethyl)phenyl]methyl b 4-(tetrahydro-2Η-jol-4-ylamino group than spit[3,4- b&gt;Bidian-5·carbamamine 87841-96〇3〇3_ in. Doc •181 - 1283678 531 2-[({[l-ethyl-4-(tetrahydro-2H-bromo-4-ylamino)-indeno[3,4-b]pyridin-5-yl]carbonyl }amino)methyl]benzoic acid methyl ester 532 N-[(6-chloro-2-ylidene)methyl]-1-ethyl-4-(tetrahydro-2H- shouting-4- Amino)pyr-pyrazolo[3,4-b]pyridine-5-carboxamide trifluoroacetate 533 N-(2,3-dichloro-1Η-indol-1-yl) small ethyl -4-(tetraqi_2H-pyran-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-formamide 534 N-({2-[ethyl fluorenyl) Methyl)amino]phenyl}methyl)-ethylethyl-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-7]pyridine-5-formamidine Amine 535 N-[(1S)_2,3-dihydro-1H-indol-1-yl]-1-ethyl_4·(tetrahydro-2H-misan-4-ylamino)-1Η-pyridyl Oxazo[3,4-b]pyridine_5-formamide 536 N-[(lR)-2,3-dichloro-1H-indol-1-yl]-1-ethyl_4_(tetrachloro_ 2H-Suppressed 4-ylamino)1Η·pyrazolo[3,4-b]pyridine-5·carboxamide 537 1-ethyl-N-({3-[(methylsulfonyl))amine Phenyl]phenyl}methyl)-4-(tetrahydro-2H-piperidin-4-ylamino)-1H-p than spit[3,4-b>pyramid-5-carbamide 538 1 -ethyl-N-(phenylmethyl)_N-propyl-4-(tetrachloro-2H-l-butan-4-yl -1H-pyrazolo[3,4-b]pyridine-5-carboxamide 540 N-[2-(dimethylamino)ethyl]-1_ethyl-N-(phenylmethyl) _4-(tetrahydro-2H-piperazin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carbamimid 541 N-butyl·1·ethyl-N- (phenylmethyl)-4-(tetrahydro-2H-pyran-4-ylamino)-lH-ρ than ton[3,4-b]lead b--5-carbamimid 542 N, l-Diethyl-N-(phenylmethyl)·4-(tetrahydro-2H-pyran-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-A Indoleamine 544 1-ethyl-N-(l-phenyl-4-p-p-decyl)-4-(tetraxan-4-ylamino)_1H-pyrazolo[3,4-b Pyridine-5_formamide 545 1-ethyl-N-{1-[(ethylamino)carbonyl]-4-hexahydropyridinyl}-4-(tetrahydro-2H- shout-4) Amino)-1Η-ρ ratio spit[3,4-b]p ratio _5-cartoamine 546 formic acid-1·ethyl-N-[l-methyl-2-(4-methyl- 1-hexachloro-exo- b-yl)ethyl]·4·(tetrahydro-2Η-piperidin-4-ylamino)-1Η-pyrazolo-P,4-b]pyridine-5-carboxamide 1:1) 547 [4-({[1·Ethyl-4-(tetrachloro-2H_^)-4-ylamino)_1Η_ρ比比[3,4-b]pyridin-5-yl]carbonyl }Amino)-1-hexahydropyridinyl]succinate methyl ester 87481-9603〇3_ Medium. Doc -182- 1283678 548 1·Ethyl-N-{[4-(4•hufolinylmethyl)phenyl]methyl}-4·(tetrahydro-2Hh-pyridylamino)_1Η- Pyrazolo[3,4-b]pyrrol-5-carbamidamine trifluoroacetate 549 1-ethyl-N-({3-[(4-methyl-1-hexahydropyrryl)) Phenyl]phenyl}methyl)-4-(tetrahydro-2H-piperazin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-formamide trifluoroacetate 550 N-{[5-(Amino-based)-3_p ratio benzyl]methyl}·1·ethyl-4·(tetrahydro-2H-pyran-4-ylamino)_1H-pyrazole [3,4-b]pyridine-5-carbamidamine trifluoroacetate 551 1-ethyl-indole-{[4-(1-methylethyl)phenyl]methyl b 4-(tetrahydro- 2H-piperazin-4-ylamino)-1Η-pyrazolo[3,4hepta]pyridin-5-formamide 552 N_{[3-(cyclopentyloxy)-4-(methoxy) Phenyl]methyl}_1_ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1Η-ρ than wow [3,4-b]p than pent-5- Amine 553 1-ethyl-N-({4-[(4-methyl-1-hexahydropyrrolidinyl)methyl]phenyl}methyl) ice (tetrahydro-2H-pyran-4-yl) Amino)-1Η-pyrazolo[3,4-b]pyridine-5-formamide trifluoroacetate 554 Ν·[(2,4·diphenyl)methyl]-1-ethyl- 4-(tetrahydro-2H-pyran-4-ylamine -1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 555 N-[(2,4-difluorophenyl)methyl]-1-ethyl winter (tetrahydro-2H -piperidinylamino)_1Η·pyrazolo[3,4_b]pyridine-5-carbamimid 556 N-[(2-nitro-4-fluorophenyl)methyl]-1-ethyl- 4·(tetrahydro-2H_ britium·4_ylamino-p-[3,4-b]p than pent-5-cartoamine 557 N-{2_[2_chloro-3-(A Oxy)phenyl]ethyl}·1·ethyl-4-(tetrazine-2H-mouth oxime-4-ylamino)·1Η·external b-[3,4-b]p -5_Artemisamine 558 3-[({[1-ethyl4-(tetrahydro-2H- brityl-4-ylamino)-[3,4_b]pyridin-5-yl]carbonyl}amine Methyl]methyl]benzoate 559 1-ethyl-N_{[3-(1-tetrahydropyrrolylmethyl)phenyl]methyl}yl (tetrahydro-2H-pyran-4-ylamine) -1Η-pyrazolo[3,4-b]pyridine-5-carbamidamine trifluoroacetate 560 1-ethyl N-(2-{4-[(methylsulfonyl)amino]benzene }}ethyl)-4-(tetrahydro^: bromo-4-ylamino)-1 Η-pyrazolo[3,4-b]pyridine-5-formamide 561 N-{[2,5 - bis(methoxy)phenyl]methyl}sodiumethyl (tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine_5_A Indoleamine 87841·96〇303·中. Doc -183- 1283678 562 N-{[2,6-Bis(methoxy)phenyl]methyl bromide ethyl ice (tetrahydro-2H-piperidin-4-ylamino)-1Η-峨峻And [3,4-b> butyl _5_methalamine 563 1-ethyl-N-[(2- phenyl)methyl]-4-(tetrachloro-2H--pyran-4-yl Amino)_1Η·ρ ratio spit[3,4-b]p than pyridine-5-carbamimid 564 N-[(3,5-a-epoxy)methyl]_1_ethyl_4-( Tetrachloro-211-0 decyl-4-ylamino)-1 Η-pyrazolo[3,4-b]pyridine_5-carbamimid 565 N-[(4-乱冬基)methyl]- 1-ethyl_4-(tetrachloro-211-0-endan-4-ylamino)_ 1H-pyrazolo[3,4-b]pyridine-5-carboxamide 567 N_cyclohexyl small B Base_4·(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 568 1-ethyl-N-{2- [4-(Methanesulfonyl)phenyl]ethyl}-4-(tetrahydro-2H-pyran-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine_5· Methionamine 569 1-ethyl-Ν·{[2·glycol-3·(trifluoromethyl)phenyl]methyl}-4-(tetrahydro-2-indole-hamo-4-ylamino) -1Η^比吐和[3,4-b&gt; 比淀-5-甲含胺570 N_({4-[(cyclopropylamino)carbonyl]phenyl}methyl)-1_ethyl-4·( Tetrahydro-2H-piperidin-4-ylamino)-1H_p than spit[3,4-b]p Precipitate-5-carbamamine 571 1·ethyl-Ν-{[4·(4_methyl-1-hexahydro-b-phenyl)phenyl]methyl}-4-(tetrahydro-2H- shout -4-4_ylamino)-1Η-external b s[3,4-b]p than yt-5-carbamamine 572 1-ethyl-N-{[4-(l_w hydrogen u than 洛基Methyl)phenyl]methyl b 4-(tetrahydro-2H-pyran-4-ylaminobipyrano[3,4-b]p than lake-5-formamide 573 1-ethyl- N-[6-(Methoxy)succinyl 2,3-dihydro·1Η- although-2-yl]-4-(tetrahydro-2H-piperidin-4-ylamino)_1H-pyridyl Zoxa[3,4-b]pyridine_5-formamide 574 N-[(2,5-dichlorophenyl)methyl]-1-ethyl-4-(tetrahydro-2H- shouting- 4-ylamino)·1Η_pyrazolo[3,4-b]pyridine_5-formamide 575 N-[(3,5-diethylphenyl)methyl]-1·ethyl· 4·(tetrahydro-2Η_»派喃-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 576 N-[(2,3-difluorophenyl) )methyl]_1_ethyl-4-(tetrahydro-2H-indol-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 577 1-B --N_{[2-(Metholyl)phenyl]methyl}_4-(tetrahydro-2H-pyran-4-ylamino)-1Η·pyrazolo[3,4-b]pyridine -5-Protonamine 578 1-ethyl-indole-[(3·light phenyl)methyl]-4-(tetraindole-2H- brim-4) Amino) lH-pyrazolo [3,4-b] pyridine-5-Amides of 87841-960303-. Doc -184 - 1283678 579 N-{[3,5-bis(methoxy)phenyl]methyldoxime-ethyl-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η -pyrido[3,4-b&gt;pyridin-5-formamide 580 1-ethyl-N-[2-(4-hydroxyphenyl)ethyl]-4-(tetrahydro-2H-piperidin喃-4-ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide 581 N-[(3,5-disorganophenyl)methyl]-1-ethyl -4-(tetrachloro-211-0 decyl-4-ylamino)-1 Η-pyrazolo[3,4-b]pyridine_5-carbamimid 582 N-{[2,4-double ( Methoxy)phenyl]methyl b; [_ethyl·4·(tetrahydro-2H-piperidin-4-ylamino)-1Η·pyrano[3,4-b]p ratio- 5-Proline 583 1-ethyl·Ν-{[2-(Methyl)-fundyl]methyl b 4-(tetrachloro-2H·*7-endan-4-ylamino)_11]&gt ;比峻和[3,4-b&gt; 比淀-5-carbamide 584 N-[(2,4-dimethylphenyl)methyl]sodiumethyl ice (tetrahydro-2H-pyran) 4-aminoamino)-1Η&gt; ton[3,4-b]p than ammonium-5-formic acid amine 585 1-ethyl-N-({2-[(methylamino)carbonyl)phenyl} Methyl) Winter (tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4_b]pyridine-5-formamide 586 1-ethyl-N_{2_[4-( Methoxy)phenyl]ethyl}-4-(tetrahydro-2H-bran-4-ylamine ))·1Η-pyrazolo[3,4-b]pyridine-5-formamide 587 N-[(2-chlorophenyl)methyl]sodiumethyl-4-(tetrahydro-2H-pyran 4-ylamino)-1H-pyrazolo[3,4_b]pyridine-5-carbamimid 588 1-ethyl_N_[(2_phenyl)methyl]-4-(tetrahydro- 2H-Bucer-4-ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carbamimid 589 N-(l,3-benzodioxan-5-yl Methyl)·1_ethyl·4-(tetrahydro-2H-peak-2-ylamino)-1Η-ρ is 唆[3,4_b]p than ·5-methylamine 590 1- Ethyl-Ν-[3-(methoxy)phenyl]-4-(tetrahydro-2Η-jol-4-ylamino)-1H-P is more than [3,4_冲比淀- 5-Protonamine 591 N-(cyclohexylmethyl)sodiumethyl-4-(tetrahydro-2H-piperidin-4-ylaminobispyrazolo[3,4-b]pyridine-5-formamidine Amine 592 1-ethyl-N-(l,2,3,4-tetrahydrosapinyl)-4_(tetrahydro-2H-pyran-4-ylamino)-1Η·^ spit and [3, 4_b]p Bishen-5-cartoamine 593 4-[({[1-ethyl_4-(tetrahydro-2H-piperidin-4-ylamino)·1Η-pyrazolo[3,4 -b] 匕 匕 -5 - 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基Tetrahydro-2H_^-an-4-ylamine-based ratio also [3,4-b]p is more than 5--5 87841-960303- in. Doc -185- 1283678 595 {·{[4-(Aminocarbonyl)phenyl]methyl}_1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1Η-pyrazole [3,4-b]pyridine-5-methanamine 596 N-[(2,6-. A 'exhaust base' methyl]-1_ethyl-4-(tetrachloro-2H-^an-4-ylamine group than ton[3,4-b]p ratio _5_甲甲胺597 N-{[3_(Amino-Williyl)phenyl]methyl}_1_ethyl·4_(tetrahydro-2H.pyrano-4-ylamino)-1Η-pyrazolo[3,4-b Pyridine-5-formamide 598 1-ethyl-indole-[(4·monophenyl)methyl]-4-(tetrahydro-2H-fluoren-4-ylamino)_ 1Η·ρ ratio唆和|;3,4 Shuai Ding-5-carbamamine 599 1-ethyl-N-{[6-(methoxy)_3_? than decyl]methyl}-4·(tetrahydro-2H -p bottom _ 4-ylamino)-1Η-ρ than spit [3,4-b]external b--5-methine 600 1-ethyl than decylmethyl)-4-(four Hydrogen-2H-p-endo-4-ylamino)_1H_pyrazolo[3,4-b]pyridine-5-carboxamide 601 1-ethyl-4-(tetrahydro-2Η-scarred- 4-ylamino)·Ν-{[3_(trifluoromethyl)phenyl]methyl}-1Η-pyrido[3,4-b>ratio·5-carbamamine 602 Ν-[ 4-(2•Amino-2-ketoethyl)phenyl]_1-ethyl·4-(tetrahydro-2-indole-scarred ylamino group is more than sir[3,4-b] Precipitate-5-cartosamine 603 1-ethyl-N-({4-[(methylamino)carbonyl]phenyl}methyl)-4-(tetrahydro-2H-pyran-4-ylamino) )-1Η·ρ比峻和[3,4-b]p 比淀-5-甲甲胺604 1 -ethyl-N-{4-[2-(methylamino)-2-ketoethyl]phenyl}_4-(tetrahydro-2H-pyran-4-ylamino)-1Η_ρ is 唆[3,4-1 Xiaobiyan-5-formic acid amine 605 1-ethyl-N-[(3-fluorophenyl)methyl]-4-(tetrahydro-2H-pyran-4-ylamino) -1H-pyrazolo[3,4-b]pyridine-5-carbamimid 606 1-ethyl-N-({4_[(methyl aryl)amino]phenyl}methyl)_4_( Tetrahydro-2H_bromo-4-ylamino group 唆[3,4-b]p ratio -5-5_甲甲胺607 N-{[4-(aminosulfonyl)phenyl]- Base)-1·ethyl-4-(tetrahydro-2Ημ trace-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-formamide 608 N-{[2 -(Aminocarbonyl)phenyl]methyl-i-ethyl_4_(tetrahydro-2Η-piperidinylamino)-1Η_ρ is 唆[3,4-b]p than -5-5_甲Amine amine 609 N-({4_[(difluoromethyl)oxy)phenyl}methyl)-1-ethyl_4-(tetrahydro-2H-bran-4-ylamino) 3,4-b]p than yt-5-cartoamine 610 N-({3-[(dimethylamino)methyl]phenyl}methyl) succinyl-4-(tetrahydro-2H- Piperazin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-decylamine 87841-960303-中. Doc -186- 611 N_{[3-Chloro-4-(methoxy)phenyl]methyl}-l-ethyl-4-(tetramethylene-2H-cyclopentan-4-ylaminol ratio Salivation [3,4-b]p is more than pent-5-cartoamine 612 N-(l_ethyl-branched-4_ττ gas ρ than decyl)-1 ethyl-4-(tetrachloro-2H· shout -4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carbamimid 613 1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino) -N_{[2_(trifluoromethyl)phenyl]methylHH-pyrazolo[3,4_b]pyridine-5-carbamimid 615 N_(5-chloro-2,3-dichloro-1H- Hetero-2_yl)small ethyl_4·(tetrachloro-2H-pyran-4)ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 616 N- ({3-[(Acetylamino)methyl)phenyl}methyl)-1_ethyl_4-(tetrahydro-2H-hydropyran-4-ylamino)-1Η-ρ ratio 并[ 3,4-b]p"b-precipitate-5-cartoamine 617 1-ethyl-N-[(4-fluorophenyl)methyl]-4.(tetrahydro-2H. britylene-4-yl Amino)-1H-P is more than [3,4-b]p than bite-5-formamide 618 1-ethyl-N-{[4-fluoroyl·2·(trifluoromethyl)benzene Methyl}·4_(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 619 1-ethyl-N_[ (2-ethylphenyl)methyl]-4-(tetrahydro-2H-piperidin-4-ylamino)-1H-pyrazole [3,4-b]pyridine-5-formamide 620 1-ethyl-N-{[2-fluoro-5-(trifluoromethyl)phenyl]methyl}-4-(tetrazine_ 2H_piperazin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 621 1-ethyl-4-(tetrahydro-2H-pyran-4) Amino)_N-[(2,3,4-trifluorophenyl)methyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide 622 N-[(4-muryl) _2_gasphenyl)methyl]-1-ethyl-4·(tetrachloro-2H-P-Chen-2-ylamino)_1Η·pyrazolo[3,4-b]pyridine-5- Methionamine 623 N-[(4-bromo-2-fluorophenyl)methyl]sodiumethyl-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[ 3,4-b]pyridine-5-carbamimid 624 Ν-[(3,5-dimethylphenyl)methyl]sodiumethyl-4-(tetrahydro-2H-pyran-4-ylamine Base)-1Η-pyrazolo[3,4-7]pyridine-5-carbamimid 625 N-[(2,3-dimethylphenyl)methyl]-1-ethylindole (tetrahydro-2H -piperidin-4-ylamino)-1Η-pyrazolo[3,4-7]pyridine_5_formamide 626 N-[(2,3-diphenyl)methyl]-1-ethyl Base (tetrahydro-2H.piperazin-4-ylamino)-1Η-pyrazolo[3,4_b]pyridine-5-carbamimid 627 N-[(4-ylyl-methylene)methyl] ·1_Ethyl-4_(Έ5-chloro-2H-bran-4-ylamino)_ 1Η-pyrazolo[3 , 4-b]pyridine-5-formamide 87841-960303-中. Doc -187- 1283678 628 Ν·[(4-bromophenyl)methyl]_i_ethyl-4-(tetrahydro-2H-pyran-4-ylamino)_ 1H-pyrazolo[3, 4-b]pyridine-5-carbamimid 629 1-ethyl-N-{[5-fluoro-2-(trifluoromethyl)phenyl]methyl}-4-(tetrahydro-2H-pyran -4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-methamine 630 1-ethyl-N-[(4-iodophenyl)methyl]-4_(four Hydrogen-2H-piperazin-4-ylamino)-1H-pyrazolo[3,4-b]pyridine-5-formamide 631 Ν-{[4-(1,1-dimethylethyl) Phenyl]methyl}_1_ethyl·4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carbamimid 632 N-[(3-cyanophenyl)methyl]-1-ethyl-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η·ρ ratios [3,4-b&gt碧丁-5-甲甲胺 633 N-[(2,6-Dichlorophenyl)methyl]-1-ethyl winter (tetrahydro-2H-piperidinyl)-111_pyrazole And [3,4-b]pyridine-5-formamide 634 N-[(5-chloro-2-methylphenyl)methyl]-1-ethyl·4·(tetrachloro-2H- shout -4-4·ylamino)-1Η-pyrazolo and i3,4-b]pyridine-5-carbamimid 635 Ν-[(3,5·二溪phenyl)methyl]-1_ethyl· 4-(tetrachloro-2H-pyran-4-ylamino)-1Η-pyrazolo[3,4_b]pyridine -5-Protonamine 636 1-ethyl-N-[(4-ethylphenyl)methyl]-4-(tetrahydro-2H-piperidin-4-ylamino)-lH-ρ ratio And [3,4-b] outside I: lake-5-cartosamine 637 1-ethyl-hydrazine·{[3-fluoro-4-(trifluoromethyl)phenyl]methyl}-4- (tetrahydro-2H.piperazin-4-ylamino)-1Η-pyrazolo[3,4_b]pyridine-5-decylamine 638 1-ethyl-N-[(2_mothyl)) -4-(tetrachloro-2H-fluorenyl-4-ylamino)_ 1H-pyrazolo[3,4-b]pyridine-5-carboxamide 639 N-[(2-bromophenyl) )methyl]-1_ethyl-4_(tetrahydro-2H-furan-4-ylamino)_ 1H-pyrazolo[3,4-b]pyridine-5-carboxamide 640 1-B -N-{[4-(demethyl)phenyl]methyl}-4-(tetrahydro-2H_ sher-4-ylamino)-1Η-pyrazolo[3,4-b] Pyridine-5-formamide 641 1-ethyl-N-{[3-(methyl)phenyl]methyl}-4-(tetrahydro-2H-pyran-4-ylamino)-111 _pyrazolo[3,4-b]pyridine-5-formamide 642 1_ethyl-N-{[3-(hydroxymethyl)_2-methylphenyl]methyl} ice (tetrahydro _ 2H-piperidin-4-ylamino)-111-0 is more than [3,4-b]p than pent-5-ylamine 643 Ν·{[2,3-dichloro-6-( Methyl)phenyl]methyl}sodiumethyl-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-ρ is more than [3,4_b&Gt; butyl--5-carbamamine 8784l-960303-zhong. Doc -188- 1283678 644 N-[(2,4-dichloro-6-methylphenyl)methyl]sodiumethyl pentyl (tetrahydroamino)-1Η-pyrazolo[3,4- b]pyridine-5-formamide 65 1_ethyl_N-{[4_(2-methylpropyl)phenyl]methyl}_4_(tetrahydro-2H-furan-4-ylamino)-1Η -pyrazolo[3,4-b]pyridine-5-formamide 646 N-[(2,5-monomethyl)methyl]-1-ethyl-4-(tetrachloro-2H -P-carbylamino)-1H-P than succinyl [3,4_b]p than 5·7-bristamine 647 1-ethyl-4-(tetrahydro-2-indole-pyran-4-ylamine Base)-Ν_[(2,4,5-trifluorophenyl)methyl]-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 648 1-ethyl-N-{[ 2_Fluoro- 4_(trifluoromethyl)phenyl]methyl}·4_(tetrahydro-2H_ 喃 -4-ylamino)-1Η^比峻[3,4-b&gt; 5-cartoamine 649 N-[(2-chloro-6-methylphenyl)methyl]_1_ethyl ice (tetrahydro-2H-pyranyl-4) base: base)·1Η-ρ ratio Also [3,4-b]p than yt-5-formic acid amine 650 4_[({[1_ethyl-4-(tetrahydro-2H- sulphonyl) 4-H-p ratio) Indolo[3,4-b]pyridin-5-yl]carbonyl}amino)methyl]benzoic acid sodium salt 651 3-[({[1-ethyl-4·(tetrahydro-2H_ shouting-4) _ylamino)-1Η-external b gorge[3,4-b]pyridin-5-yl] 】}amino)methyl]benzoic acid 652 1-ethyl-4·{[4_(imido)cyclohexyl]amino}_1H-pyrazolo[3,4-b]pyridine-5-carboxylate Ethyl acetate 653 1_ethyl_4-{[4-(hydroxyimino)cyclohexyl]amino}-N-{[4-(methoxy)phenyl]methyl}-1Η-ρ ratio Salivation [3,4-b]pyrazine-5-formamide 654 N-{[4-(dimethylamino)phenyl]methyl}-1_ethyl·4-{[4-(hydroxy Imino)cyclohexyl]amino}-1Η-pyrazolo[3,4-b]pyridine-5-formamide 655 1-ethyl-4_({4-[(ethoxy))imido) Cyclohexyl}amino)-N-{[4-(methoxy)phenyl]methyl}-1Η·pyrido[3,4-b>pyridyl-5-carbamide 656 1_B 4-({4-[(methoxy)imino]cyclohexyl)amino)-N-{[4-(methoxy)phenyl]methyl b 1H-pyrazolo[3, 4-b]pyridine-5-formamide 657 4-[(4-{[(1,1·dimethylethyl)oxy]imino]cyclohexyl)amino]·1·ethyl- Ν-{[4-(Methoxy)phenyl]methyl b 1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 658 1_ethyl-N-{[4_(methoxy Phenyl]methyl}-4-[(7-ketohexahydro_1H-qi-7-yl-4-yl)amino]pyrazine[3,4-b]p than lake-5- A brewing amine 8784l-960303-zhong. Doc -189- 1283678 659 1_Ethyl_4-[(7-ketohexahydro-1H-azadecen-4-yl)amino]_1Η·pyrazolo[3,4-b]pyridine -5-Carboxylic acid ethyl ester 660 4-{[cis-4.(butylamino)cyclohexyl]aminophenyl n_(2,3-dihydro-1H-indol-2-yl)_1_ethyl -1Η·ρ比峻和[3,4-b]峨盐-5-Proline 661 4_[(trans-4-AminoJ-hexyl)amino]-i-ethyl (phenylmethyl) Bisazo[3,4-b]pyridine-5-carbamimid 662 4_[(trans-2-aminocyclohexyl)amino]xiaoethyl·Ν_(phenylindenyl)_1]9[_ Pyrazolo[3,4-b]pyridine-5-formamide 663 4-[(cis-2-aminocyclohexyl)amino]_1_ethyl_N_(phenylmethyloxazolidine [3] ,4-b]pyridine-5-methanamine 664 4-[(3·Amino- hexyl)amino]-1-ethyl(phenylmethyl)_1Η-ρ than 唆[3,4-b ]p-precipitate-5-formic acid amine free example 1: 4_(cyclopentylamino)-1-ethyl-111_pyrido[3,4-b]pyridine-5-oleic acid ethyl ester

Intermediate 1 (0.051 g) and cyclopentylamine (0.019 g) were suspended in ethanol (2 mL) and triethylamine (0.14 mL). The mixture was stirred under nitrogen and heated at 80 ° C for 16 hours. After cooling to room temperature, the ethanol was removed by evaporation under a stream of nitrogen, and the residue was partitioned between di-methane (DCM) and water. The liquid layer was separated, and the organic layer was directly loaded on a solid phase extraction (SPE) cartridge (silicone, 5 g), which was successively used; (i) DCM, (9) DCM: Et2 (2: 1), (iii) DCM : Et 2 Ο (1 : 1), (iv) Et 2 0, (v) EtOAc, (vi) MeOH. The fractions containing the desired material of 87841-960303···doc -190-1283678 were combined and concentrated in vacuo to give an example 丨(〇 〇 74 g). LCMS shows MH+ = 303; Tret = 3.45 min. 0 The following materials were prepared in a similar manner: NHR3

NHR3 amine reagent ΜΗ+ion TRET (minutes) Example 2 hn-cyclohexylamine 317 3.65 Example 3 ηνΌ 4-aminotetrahydropyran 319 2.93 Example 4 ΗΝ 乂)ι an intermediate 7 332 2.17 Example 5 Intermediate 6 360 3.20 Rehabilitation "1 (= intermediate 32): 1-ethyl winter (tetrazol-2 Η·ι 喃 _4_ ylamino)-iH_pyrazolo[3,4_b] 峨 ___ Ethyl carboxylate

Instead of the method shown above (referred to as Method A), the compound of Example 3 can also be prepared using the following procedure: Example 3, Method B: Intermediate 1 (25 g) was dissolved in acetonitrile (15 mL) . 4-Aminotetrahydropyran hydrochloride (11 g) and N,N-diisopropylethylamine (9 4 mL) were added and the mixture was stirred under nitrogen and EtOAc for 16 hr. A trace amount of the starting material was left. Thus, another portion of the amidotetrahydropyran hydrochloride (〇 11 g) was added, and stirring was continued at 85 C for further 16 hours. The mixture was then concentrated in vacuo. The residue was partitioned between DCM and water. The layers were separated, and the organic layer was washed with water (2.times.20 mL), then dried (Na2S04) and concentrated in vacuo. The residue was further chromatographed, purified using EtOAc (EtOAc) (EtOAc) LCMS showed MH+ = 319; Tret = 2.90 min. Example 6: Ethyl 4-(cyclopentylamino)_1-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate X)

Intermediate 3 (0.045 g) was placed in ReactivialTM and treated with cyclopentylamine (〇_〇 7 mL). The mixture was heated at 90 °C for 2 hours, then cooled to room temperature and partitioned between chloroform (2 mL) and water (1 mL). The layers were separated and the organic phase was evaporated to a white solid. LCMS showed MH+ = 289; Tret = 3.22 min. f Example 7: 1-methyl_4_(tetrahydro-2H4py-4-ylamino)-1Η-pyrazolo[3,4-b]pyridin-5-carboxylic acid ethyl ester

Intermediate 3 (0.035 g) was placed in ReactivialTM and treated with the present amine tetrahydropyran (0.06 mL). The mixture was heated at 9 (rc for 2 hours, then allowed to cool to room temperature and separated between chloroform (2 ml) and water (4) liters) 87041_96〇3〇3·中.doc -192-1283678 Reason. The liquid layer was separated and the organic phase was concentrated, then applied to a preparative TLC plate (tank, 20 cm x 20 cm x 1 mm), which was dissolved in ethyl acetate. The absorbent tape required for the removal of the plate was washed with ethyl acetate (2 χ 15 ml). The ethyl acetate solution was concentrated in vacuo to afford crystals as a white solid (0.008 g). LCMS showed MH+==:305 and Tret = 2.67 min. Actually shoulder: 1-ethyl-4-[(3S)-four atmospheres of 17-propanylamino group] than 丨 丨 3,4_b]p ratio pyridine-5-carboxylic acid ethyl ester

中间 Suspend Intermediate 1 (0.05 g) and (S)_(+3-aminotetrahydrofurfuryl 4-toluene hydrochloride (0·052 g) in ethanol (丨 ml) and add triethylamine (〇 14 ml). The mixture was stirred under nitrogen and heated at 80 ° C for 24 hours. After cooling to / after - the ethanol was removed by evaporation under a stream of nitrogen, and the residue was taken in dCM (2 liters) Separate the mixture with water (1.5 ml). The layers were separated and the organic layer was concentrated to dryness. Purified with EtOAc (EtOAc: EtOAc) 16, then i: 8, i: 4, i: 2, i: 1 and work: 〇) Dissolution. The dissolved fractions containing the desired substances are combined and concentrated in vacuo to give Example 8 (0·〇52 g LCMS shows Gu += 3〇5; Ding New = 2·7〇 minutes. The following materials were prepared in a similar manner: 87841-960303-ψ.άοο -193- 1283678

NHR3 Amine Reagent MH+ Ion Tret (minutes) Example 9 (R)-(+)-3_Aminotetrahydrofurfuryl 4-toluenesulfonate 305 2.73 Example 10 Intermediate 11 335 3.21 Example 11 Mixture) Intermediate 12 321 3.10 Example 12 ΝΗ Cyclopropylamine 275 2.98 Child-Example: Our team 1-dihydropyrimidinylamino) hydrazine-ethyl-1H-pyrazolo[3,4_b] Pyridine-5-carboxylic acid ethyl ester

Intermediate 1 (0.05 g) and intermediate 13 (0.027 g) were suspended in ethanol (1 mL) and triethylamine (0.14 mL). The mixture was stirred under nitrogen and heated at 80 ° C for 24 hours. After cooling to room temperature, the ethanol was removed by evaporation under a nitrogen stream, and the residue was partitioned between DCM (2 mL) and water (1.5 mL). The layers were separated and the organic layer was concentrated to dryness. Purification was carried out using a SPE cartridge (silica gel, 5 g) eluting with a gradient of EtOAc: hexanes; (1:8, then 1:4, 1:2,1··1 and 1··0). The fractions containing the desired material were combined and concentrated in vacuo to give EtOAc (EtOAc: EtOAc) LCMS showed MH+ = 353; Tret = 2.60 min. The following materials were prepared in a similar manner: NHR3

C〇2Et NHR3 Amine reagent MH+ ion TRET (minutes) Example 14 hnXDsC Intermediate 14 367 2.64 Free Example I9 (Refer to J case, as intermediate): 4-(cyclopentylamino)-1Η-pyrazolo[3 , 4-b]p than the lake -5 - acid

Example 19 NHR3 = hn-〇 Intermediate 2 (0.035 g) was placed in ReactivialTM and treated with cyclopentylamine (〇·〇 5 mL). The mixture was heated at 90 ° C for 1.5 hours, then allowed to cool to room temperature and was partitioned between chloroform (2 mL) and water (1 mL). The liquid layer was separated&apos; and the organic phase was concentrated. The residual solid was triturated with Et, and an insoluble off-white solid was collected and dried to give Example 19 (0.016 g). LCMS showed MH+ = 275; Tret = 2.58 min. t Example 2〇 (Refer to L.· as an intermediate)································ Ethyl carboxylate 87841-960303-φ.άοο -195- 1283678

Intermediate 2 (0.035 g) was placed in ReactiviaiTM and treated with i-amine meglumine (0. 05 mL). The mixture was heated under 9 Torr for 15 hours, then cooled to room temperature and partitioned between chloroform (2 mL) and water (1 mL). The layers were separated and the organic phase was concentrated. The crude product was purified by preparative HPLC eluting with EtOAc EtOAc (EtOAc) LCMS showed MH+ == 291; Tret = 2.08 min. Alternative Synthetic Method for Example 20: Intermediate 2 (2 g) was suspended in 4-aminotetrahydropyran (2 g) and the mixture was heated at 90 °C for 6 hours. The residual mixture was cooled to room temperature and partitioned between chloroform (50 ml) and water (50 ml). The liquid phase is separated and the organic phase is evaporated to dryness. The residue was triturated with EtOAc (3 mL). LCMS showed MH+ = 291; Tret = 2.19 min. m 21· : N-benzyl small ethyl winter (tetrahydro-tornyl amyl) · 1Η-Ρ than spit [3,4-b]pyridine-5-carbamide 196· 87841_96〇3 〇3·中d〇c 1283678

nrV material _5=^0 NHR3= m^y Three alternative methods A, B and C have been used to make Example 21, as follows: Example 21, Method A: 4-Chloro intermediate 17 (0.031 g, 〇 · 1 millimolar) solution in ethanol (L9 ml) 'with triethylamine (0.07 ml, 0.5 mmol), followed by 4-aminotetrahydropyrene oxime · 1 Μ methanol solution (intermediate 8, U ml, 01M with ethanol solution = 〇 · 11 millimoles). The mixture was heated under reflux (8 (rc) for 18 hours. Then another portion of 4-amino-tetrahydrofuran (〇·〇ι ml undiluted amine, not a solution) was added and heating was continued for another 24 hours. The volatiles were removed in vacuo and the residue was dissolved in dichloromethane (DCM) then applied to a solid phase extraction (SPE) cartridge (aminopropyl, 1 gram) which was firstly taken in DCM Then, it was dissolved in methanol, and the fractions containing the desired substance were concentrated in vacuo to give Example 21 (0.004 g). 1^:]\48 showed _+=380;1^== 2.92 min. Example 21, Method B : Intermediate 17 (0.031 g, 0.1 mmol) was dissolved in acetonitrile (1 mL). 4-Aminotetrahydropyran hydrochloride (Intermediate 8A, 15 g, 〇11 mmol) And N,N-diisopropylethylamine (8 ml, 〇·5 mmol), and the mixture was stirred under nitrogen and 85 C for 16 hr then concentrated in vacuo. 87841-96〇3〇3·中.doc -197- 1283678 Dichloromethane (DCM) was partitioned between water and water. The liquid layer was separated and the organic layer was concentrated in vacuo to give Example 21 (0) .027 g) LCMS showed MH+ = 380; TRET = 2.92 min. Example 21, Method C: This alternative route c of Example 21 relates to Example 3 Ester = Intermediate 32

Formation of 'Using the above method' - using the method described above for Intermediate 33, the ester/intermediate 32 of Example 3 was converted to the carboxylic acid (Intermediate 33), and then the following Examples 81-84 were used. Method, a guanamine bond formation was made to form Example 21. The following compounds can be prepared in a similar manner using one or more of the above methods A, B or c, preferably Process A or B:

NR4R5 NHR3 Starting material Amine reagent ΜΗ+-ion 384 Tret (minutes) 3.09 Example 22 ηνΌ Intermediate 19 4_Amino tetrahydro sulphonate Example 23 ονη ΗΝΌ Intermediate 20 Cyclopentylamine 342 3.29 Example 24 crNH ηνΌ Intermediate 20 Cyclohexylamine 356 3.47 87841-960303-^.doc -198- 1283678 Example 25 CrHH~ ην-〇 intermediate 20 ------- 4·Amino tetrahydrogen 358 2.79 Example 27 CrNH Μ Intermediate 20 Intermediate 6 400 2.64 Example 28 Ο ην^ο Intermediate 21 Cyclopentylamine 328 2.69 Example 29 RT ηνΌ Intermediate 21 Cyclohexylamine 342 2.87 Example 30 ό ΗΝ-^ ) 〇 Intermediate 21 4-Aminotetrahydropyran 344 2.33 Example 31 ην^ο Intermediate 22 Cyclopentylamine 365 2.38 Example 32 ην~0 Intermediate 22 Cyclohexyl 379 2.54 Example 33 ΗΝ々γ^ι ηνΌ Intermediate 22 4-Aminotetrahydropyran 381 2.09 Example 34 Ηη2 ΗΝ^ Intermediate 24 Cyclopentylamine 274 2.59 Example 35 νη2 ην-〇 Intermediate 24 Cyclohexylamine 288 2.79 Example 36 νη2 ΗΝ—^ ^0 Intermediate 24 4-Aminotetrahydropyran 290 2.22 Rabbit Example.39 : N-benzyl bucket (cyclopentylamino) small ethyl-1H-pyrazole [3,4-7] Pyridine-5-formamide 87841-96〇3〇3_中.doc -199- 1283678

Nr4r5 where NR4R5=: NHR3= a solution of intermediate 17 (0.031 g, 〇 吝 seedling 1+, 、, 莫莫) in ethanol (1 ml) with diethylamine (0.07 liters, 〇_5 The ear of the tomb, and the second!, the pen Moer) is connected with a 0.1M ethanol solution of cyclopentylamine (1.1 ml, (^ said ethanol containing π / combined / from uu pen Moer). Heating under reflux (_) for 1 Torr, then adding another portion of cyclopentylamine _9 ml of undiluted amine, not a solution thereof, and heating was continued for an additional hour. The volatiles were removed in vacuo and the residue was taken up in Dcm then applied to &lt;RTI ID=0.0&gt;&gt;&gt; The DCM fractions were concentrated in vacuo, then applied to a spE cartridge (yield: &lt;RTI ID=0.0&gt;&gt; The fractions containing the desired material were combined to give Example 39 (0·0〇7 g). LCMS showed ΜΗ+=364; Tret=3.38 min. The following materials were prepared in a similar manner:

87841-960303-中.doc -200- 1283678 nr4r5 NHR3 Starting material Amine reagent MH+ Ion Tret (minutes) Example 40 HNT) Intermediate 17 Cyclohexylamine 378 3.43 Example 41 HNT) hn-〇^° Intermediate 17 Intermediate 6 42 1 2.75 Example 42 HN. HN~O Intermediate 18 Cyclopentylamine 358 3.63 Example 43 HN. &quot;Ο Intermediate 18 Cyclohexylamine 372 3.79 Example 44 HN. hn~0 Intermediate 18 4-Amino Tetrachloride L. 374 3.13 Example 45 HN. HN—^ yj—Intermediate 18 Intermediate 7 387 2.37 Example 46 HN. HN—^ Intermediate 18 Intermediate 6 415 2.92 Example 47 F hn^O Intermediate 19 Cyclopentylamine 368 3.61 Example 48 HN-F hn-〇 intermediate 19 cyclohexylamine 382 3.76 Example 49 F hn-CZ/*~ Intermediate 19 Intermediate 7 397 2.29 Example 50 F --0-Λ0 Intermediate 19 Intermediate 6 425 2.88 Example 51 HN,^HN-〇 intermediate 23 cyclopentylamine 316 3.05 Example 52 hn&lt;3 intermediate 23 cyclohexylamine 330 3.26 Example 53 HN 八'^ HN-^ \) Intermediate 23 4_Amino tetrachloro 332 2.58 Example 55 hn{M〇Intermediate 23 Intermediate 6 373 2.46 87841-960303-中.doc -201 - 1283678 Realization · N•Yuji+Ethyl Yl -piperidin-4-yl) amino] _1H- pyrazolo [3,4_b] pyridine-5-Amides

A solution of the intermediate 17 (0.031 g, ι·ι mmol) in ethanol (1 mL) was taken as diethylamine ( 〇 〇 〇 〇 〇 5 5 5 5 5 5 5 5 5 5 .1M [containing ethanol drop (1.1 ml solution = 0. U millimoles). The mixture was heated under reflux (80 C) for 18 hours. Then another intermediate 7 (〇.〇1 ml) of undiluted amine was added and heating was continued for another 24 hours. The volatile material was removed in vacuo and the residue was dissolved in DCM then applied to a SPE cartridge (aminopropyl, 1 gram) which was first eluted with DCM then methanol. The DCM fractions were concentrated in vacuo and then applied to a EtOAc EtOAc (EtOAc) (EtOAc) The methanol fractions were concentrated and further purified by SPE (silica gel, 0.5 g) in steps of (i) DCM, (ii) EtOAc and (iii) EMI:MeOH (from 99:1 up to 4:1) Gradient dissolution. The fractions containing the desired material were combined to give Example 56 (0.004 g). 1^]^8 shows]^+=393; 1^^=2.26 minutes. Example 57: 4-[(1_Ethyl hexafluoropyridinyl-4-yl)amino]]ethylethyl-hydrazine-(ρ 咬-4-ylmethyl)_1Η-pyrene[3,4 -b]pyridine_5_formamamine 87841·96〇3〇3_中.doc -202- 1283678 Λ

Et

NR4r5 where NR4R5 =

NHR3 = HN 〇 The intermediate 22_g 'about w millimoles' in ethanol (four) liters, to triethylamine (_ml, 0.5 millimolar), followed by the towel ^ o.im Treatment with B solution (u ml solution = 〇 11 mmol). The mixture was heated at reflux for 1 M. It is difficult to add another intermediate 6-ml 'undiluted' and continue heating for 24 hours. The volatiles are removed in vacuo and the residue is dissolved in DCM, then applied to the spE cartridge (aminopropyl) , 1 g), which was first dissolved in DCM and then methanol. The DCM fractions were decanted in vacuo and applied to a spE cartridge (矽, 5 g) to (i) DCM, (ii) EtOAc and (out) chloroform:methanol (from 99:1 up to 4: 1) Step gradient elution. The fractions containing the desired material were combined to give Example 57 (0.003 g). LCMS showed MH+ = 422; TRET = 2.1 min. Free of Example 61 ·········································

87841-960303-nfJ.doc -203 - 1283678 A solution of intermediate 28 (0.03 g, (U millimolar) in ethanol (1 ml) with a solution of cyclopentylamine in 0.1 M ethanol (u ml solution = 〇 Then, add triethylamine _ml, 〇.5 mM), and the mixture is heated under reflux (85 〇 and under nitrogen), then add another portion of cyclopentylamine (9 ml) 'Undiluted' and heating for an additional 36 hours. Concentrate the mixture in vacuo and treat the residue with chloroform. Collect a small amount of insoluble material by hydrazine' and then apply the filtrate to the SPE cartridge (aminopropyl, 1 g ), which is first viewed in a view, followed by elution with the f alcohol. The dissolved fractions containing the desired material are combined to give an example Μ (〇.〇 39 g). LCMS shows hall += MO; Tret = 2 minutes. In a similar manner Prepare the following substances··

NR4R5 NHR3 Starting material Amine reagent ΜΗ+ Ion Tret (minutes) Example 62 HN^〇ηνΟ Intermediate 28 Cyclohexylamine 364 3.05 Example 63 HNXi ηνΓ&quot; ΗΝ·~^ ) 〇Intermediate 28 4·Amino tetrahydron 366 2.52 Example 64 ΗΝ. -——— Intermediate 30 Cyclopentylamine 344 3.06 Example 65 ηνΙ~ '- ηνΌ Intermediate 30 Cyclohexylamine 358 3.23 Example 66 ην~Ό Intermediate 30 1----- 4_amine Base tetrahydrogenethane 360 2.69 87841-96〇3〇3·中.doc -204 - 1283678 Example 67 F HNO Intermediate 29 cyclopentylamine 354 3.17 Example 68 ΗΝ—^^κ-F hnhO Intermediate 29 Cyclohexylamine 368 3.33 Example 69 HN-F hnO Intermediate 29 4-Aminotetrahydro brigade 370 2.72 Example 70 nh2 Intermediate 31 Cyclopentylamine 260 2.10 Example 71 nh2 Intermediate 31 Cyclohexylamine 274 2.29 Example 72 nh2 hnO Intermediate 31 4-Aminotetrahydropyrene 276 1.86 Example 74: 4-[(1_Ethyl hexahydropyridyl) yl]benzyl small methyl-1H-pyrazolo[3,4-b]pyridine -5_Metamine

Where I NR4R5 = NHR3 =

A solution of Intermediate 28 (0.03 g, 0.1 mmol) in ethanol (1 mL) was taken and taken from &lt;RTI ID=0.0&gt;&gt; Then triethylamine (0.07 ml, 〇. 5 mmol) was added, and the mixture was heated under reflux (85 ° C) and nitrogen for 12 hr. An additional intermediate 6 (0.1 mmol) was then added and heating was continued for an additional 36 hours. The mixture was concentrated in a vacuum of 87841-96 〇 3 〇 3 _ doc - 205 - 1283 678 and the residue was treated with chloroform. A small amount of insoluble material was collected by filtration, and then the filtrate was applied to a SI&gt;E cartridge (aminopropyl, gram) which was first dissolved in DCM followed by methanol. The fractions containing the desired material were combined and concentrated in vacuo. The residue was further purified by step-wise gradient elution of (1) DCM, (9) milk, (iii) EtOAc and (iv) chloroform:methanol (from 99:1 to the same 4·1). . The fractions containing the desired material were combined to give Example 74 (0.029 g). LCMS showed mh+^ surgery; Tret = 2 57 minutes. The following materials were prepared in a similar manner:

Nr4r5 hn, NHR3 starting material amine reagent MH+ ion Tret (minutes) Example 76 HN—^ Intermediate 30 Intermediate 6 401 2.74 Example 78 hn^C3~~f Intermediate 29 Intermediate 6 411 2.69 Really Shame·1-B Methyl methyl winter (tetrahydro-2H-chloropyran-4-ylamino)-1Η-pyrido[3,4-b]pyridine-5-carbamide

Example 81 NR4R5 = NHMe 87841-960303-中.doc • 206· 1283678 in the intermediate 33 (0·025 g, approx. (4) to _mole) in chloroform (2 mAh in the stirred suspension, $plus Thionine ruthenium chloride (5 ml), and the mixture was stirred at room temperature for a few hours. The mixture was cooled to hydrazine: and methylamine (2M solution in THF, EtOAc &lt;RTI ID=0.0&gt; After returning to room temperature, the mixture was stirred for an additional hour, then the reaction was quenched by the addition of water (4 mL) and the layers were separated. The organic layer was concentrated and then applied to a spE cartridge (silicone, 1 g), which was (i) DCM, (9) Et2 (2: 1}, (iv) Et〇Ac, (d)

MeOH : EtOAc (1:9) was dissolved. The fractions containing the desired material were combined and Example 81 (0.019 g) was obtained. 1^^18 shows 1^111+=304; 1^£;1^=2.19 minutes. The following materials were prepared in a similar manner:

Nr4r5 amine reagent MH+ ion Tret (minutes) Example 82 NMe2 dimethylamine (2M in THF) 318 2.06 Example 83 NHEt ethylamine (2M in THF) 318 2.31 Example 84 NHiPr isopropylamine (2M in THF) 332 2.44 f Example 83: N,l-diethyl-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine_5_ formazan Amine; also known as 1-ethyl-N-ethyl-4-(tetrahydro-2H.piperidin-4-ylamino)-1Η-pyrazolo[3,4_b]pyridine-5-carboxamide 87841-960303-ψ.άοο -207- 1283678

In an alternative embodiment to the above examples 81-84, Example 83 can be made according to the following method: intermediate 33 (3 gram, 1 〇 33 millimoles), EDC (2.25 gram, A mixture of 11.7 millimoles) and hydrazine (1. 68 grams, 12.4 millimoles) was stirred at room temperature for 1 hour. Ethylamine (6.2 ml, 12_4 mmol, 2 Μ in THF) was added and stirring was continued at room temperature for 22 hours. The solvent was removed in vacuo and the residual solid was dissolved in chloroform (250 mL). After dehydration and drying with anhydrous sodium sulfate, the organic solution was evaporated in vacuo to give a pale orange solid (4·15 g). This solid was dissolved in a mixture of dichloromethane (15 mL) and EtOAc (5 mL). ) and finally dissolved in pure EtOAc. The product-containing fractions were combined and evaporated to give a crystallite. LCMS showed MH+ = 318; Tret = 2.33 min. ^NMR (400 MHz in d6-DMSO, 27 °C, (5 ppm) 9.76 (d,1H) 8.35 (s,1H) 7.94 (s, 1H) 5.99 (br m,1H) 4.47 (q,2H) 4.16-4.01 (m, s, 3H) 3.62 (m, 2H) 3.48 (m, 2H) 2.13 (m, 2H) 1.77 (m, 2H) 1·49 (t, 3H) 1.28 (t, 3H)· Example 85 : N-benzyl-1-ethyl-4-[(3S)-tetrahydrofuran-3-ylamino]_1H-pyrazolo[3,4_b]pyridine-5-carboxamide 87841-960303-中. Doc -208 - 1283678

Intermediate 41 (0.017 g, 0.062 mmol) was dissolved in DMF (2 mL) then EtOAc (EtOAc: EtOAc) 10 minutes. Then benzylamine (0.007 ml) was added and stirring was continued for a further 64 hours. The mixture was concentrated in vacuo and EtOAc EtOAc m. The mixture was stirred for 30 minutes, then the layers were separated and the organic layer was applied to a SPE cartridge (tank, 1 g), which was successively taken in ethyl acetate: cyclohexane gradient (1 ··4, then 1: 2, 1 : 1, 2 : 1 and 1: 0) Dissolution. The fractions containing the desired material were concentrated in vacuo to give Example 85 (0.017 g). LCMS showed MH+ = 366; Tret = 2.80 min. The following materials were prepared in a similar manner:

87841-960303-中.doc -209 - 1283678 NHR3 Starting material Tre τ (minutes) Example 86 Intermediate 42 366 2.80 Example 87 中间 Intermediate 44 382 3.11 Example 88 ^ΝΗ LJM —----- Intermediate 45 336 3.00 Example 89 ΠΙΝ^ XX 0 Intermediate 46 414 2.69 Example 90 hM0&lt; Intermediate 47 428 2.75 i·Example 91 : N-Benzylethyl_4_(tetrahydro-2Η_thiopipene_4_yl Amino)_1H-pyrazolo[3,4_b]pyridine_5-formamide

Intermediate 43 (0.019 g) was dissolved in DMF (2 mL) thenEtOAc (EtOAc) Then benzylamine (7 ml) was added and stirring was continued for another 64 hours. The mixture was concentrated in EtOAc (EtOAc m. This mixture was stirred for 30 minutes, then the layers were separated, and the organic layer was applied to a SpE cartridge (m.m., 1 g), which was successively taken in ethyl acetate: cyclohexane gradient (1:4, then 1: 2, 1 : 1 and 1 ·· 〇) Dissolution. The fractions containing the desired material were concentrated in vacuo to give Example 91 (0·23 g). LCMS showed MH+ = 396; Tret = 3.26 min. Rabbit Example 92: [Ethylfluorophenyl]-4_[(3S)-tetrahydrofuran-3-ylamino]-1H-pyridyl-210- 87841-960303-cjn, doc 1283678 oxazo[3,4-7]pyridine _5_Metamine

Intermediate 41 (0.017 g) was dissolved in DMF (2 mL) thenEtOAc (EtOAc:EtOAc) Then, 4-fluoroaniline (〇6 ml) was added, and stirring was continued for another 64 hours. The mixture was concentrated in vacuo and EtOAc EtOAc m. The mixture was stirred for 3 minutes, then the layers were separated and the organic layer was concentrated in vacuo. The crude mixture was purified by preparative HPLC by mass guidance to give Example 92 (0.013 g). LCMS showed ΜΗ+=370; Tret=2.91 min. The following materials were prepared in a similar manner:

87841-96〇3〇3·中.doc -211 · 1283678 NHR3 Starting material ΜΗ+ion Tret (minutes) Example 93 Example 94 Example 9S Example 96 Example 97 ---^ NH Intermediate 42 370 2.91 ηνΌ Intermediate 43 400 ----- 3.37 Intermediate 44 386 3.27 Λ. \ΝΗ Intermediate 45 340 3.21 ΗΝ, η Intermediate 46 418 2.80 Example 98 -- ηνΚ^Χ Intermediate 47 432 &quot;----- 2.84 Example 99 In all of Examples 22 to 98, in the case where the 4-amino-5-carbamyl-------1 amine of the following formula I has been synthesized from a 4-chloro derivative, The final step of synthesis is as follows:

The intermediate of formula IV above (Q1 millimolar) was dissolved in acetonitrile (Q mL). Add R^NH2 amine (0.U penmoule, u molar equivalent) and slightly diisodecylethylamine (pen Moer '5 molar equivalent), and mix the mixture under nitrogen and hunger After the reduction in the true two, the residue was treated with dichloromethane (DCM) and water (intermediate with a knife solution. The liquid layer was separated and the organic layer was concentrated in vacuo to give an example of formula I. Example 100 -212- 87841-96〇3〇3_ Medium.doc 1283678

Intermediate 33 (0.048 mmol) was dissolved in DMF (0.5 mL) then treated with HATU (0.048 mmol) followed by diisopropylethylamine (0.096 m) and mixture was stirred 10 minute. Next, 4-methanesulfonylbenzylamine (0.052 mmol, available from Acros organic) was added and stirring was continued for an additional 16 hours. The mixture was concentrated in vacuo. The crude mixture was purified by preparative HPLC eluting with mass to give Example 100 (0.013 g). LCMS showed MH+ = 458; TRET = 2.22 min. The following compounds were prepared in a similar manner except that the other amine, R4R5NH, of the same or similar molar number was substituted for 4-methanesulfonylguanamine:

87841·96〇3〇3·中.doc -213 - 1283678 NR4R5 (N atomic system linked to R4 and R5 to -CO-pyrazolo-pyridine partial base is drawn to the bottom line) Source of starting material MH+ ion of r4r5nh Tret (minutes) Example 101 CX/N °VCH3 Th36 CH3 AstaTech Corporation 8301 Torresdale Ave. 19C, Philadelphia, PA, 19136, USA Intermediate 33 487 2.29 Example 102 /, 〇J. Chem. Soc.} 1945, 633 Middle Object 33 458 2.2 Example 103 C〇^F ch3 WO 98/52943 Intermediate 33 490 2.66 Example 104 J· Org·Chem” \9Ί9, 44(3), 396 Intermediate 33 415 2.28 Example 105 Seriya Khimicheskaya^ 1989, (7) , 1694 Intermediate 33 456 2.65 Example 106 H〇/^cl SALOR (Aldrich) Intermediate 33 458 2.32 Example 107 H3C, Maybridge Chemical Company Trevillett Tintagel Cornwall PL34 0HW United Kingdom Intermediate 33 461 2.5 Example 108 MicroChemistry-RadaPharma Shosse Entusiastov 56 Moscow, 111123 Russia Intermediate 33 390 2.28 Example 109 MicroChemistry-RadaPharma Shosse Entusiastov 56 Moscow, 111123 Russia Intermediate 33 387 2.13 -214- 87841-960303-中.doc 1283678 Examples 110 Bulletin des Societes Chimiques Beiges, (1982), 91(2), 153 Intermediate 33 382 1.98 Example 111 ΗΝ/Χ^Ν, &quot;XVch3 \s MicroChemistry-RadaPharma Shosse Entusiastov 56 Moscow, 111123 Russia Intermediate 33 401 2.14 Example 112 HNn^O^〇XCH3 h3c ch3 Intermediate 33 466 2.67 Example 113 V CH3 ch3 Ultrafine (UFC), see above address intermediate 33 425 2 Example 114 Austin Chemical Company 1565 Barclay Blvd. Buffalo Grove, IL, 60089 USA Intermediate 33 382 2 Example 115 03⁄4 WO 02/83624 Intermediate 33 464 1.97 Example 116 cr Fluka Chemie AG Intermediate 33 432 2.52 Example 117 H MicroChemistry-RadaPharma Shosse Entusiastov 56 Moscow, 111123 Russia Intermediate 33 397 1.96 Example 118 0 WO 02/85860 Intermediate 33 423 2.09 Example 119 0 Butt Park Braysdown Works Peasedown St. John Bath, BA2 8LL, United Kingdom Intermediate 33 423 2.19 Example 120 N^/ Sigma Intermediate 33 398 1.77 Example 121 y~N\ . b US 4562184 Intermediate 33 452 2.21 Example 122 n, n// Dynamit Nobel GmbH, Germany; or Saville Whittle Ltd (UK agents of Dynamit Nobel), Vickers Street, Manchester M40 8EF, United Kingdom Intermediate 33 372 1.93 87841-960303 - 中.doc -215-1283678 Example 123 N^/WO 02/66470 Intermediate 33 385 1.93 Example 124 Η υΜ3 J. Med. Chem., 1990, 33(1), 97 Intermediate 33 447 2.17 Example 125 Aldrich Intermediate Object 33 434 2.84 Example 126 ^χν:; AstaTech, Inc. 8301 Torresdale Ave. 19C5 Philadelphia, PA, 19136, USA Intermediate 33 473 2.5 Example 127 hn^^ns^ch3 Intermediate 33 425 1.99 Example 128 H3C/N, CH3 J. Org. Chem., 2001, 66(6), 1999 Intermediate 33 423 1.97 Example 129 ΗΝ. (|}Ν,Η3 Acros Organic Intermediate 33 401 1.82 Example 130 〆Aldrich Intermediate 33 374 2.08 Example 131 idN. n Combi-Blocks, Inc. 7949 Silverton Av. 5 Suite 915, San Diego, CA 92126, USA (see also Intermediate 8A) Intermediate 33 374 2.04 Example 132 〇◊, 〇 J. Org·Chem,, 1955, 20, 1657 Intermediate 33 487 2.39 Example 133 HN. 〇1, ch3 0 J. M Ed. Chem., 1999, 42(14), 2504; or variant: Lis et al., /. Med. Chem., 1990, 33(10), 2883, see Figure III Reference 24 Intermediate 33 473 2.24 Example 134 0 Tetrahedron, 1992, 48(29), 6161 Intermediate 33 401 1.97 Example 135 Aldrich Intermediate 33 396 2.42

87841-960303-中.doc-216- 1283678 Example 136 HN. &quot;V Aldrich Intermediate 33 415 2.03 Example 137 ch3 Aldrich Intermediate 33 401 1.78 Example 138 Aldrich Intermediate 33 381 1.81 Example 139 MicroChemistry-RadaPharma Shosse Entusiastov 56 Moscow , 111123 Russia Intermediate 33 387 1.74 Example 140 CH. \ch3 Aldrich Intermediate 33 360 2.16 Example 141 Aldrich Intermediate 33 401 1.81 Example 142 HNv^ 0 Aldrich Intermediate 33 417 1.75 Example 143 ldik^^〇vCH3 Aldrich Intermediate 33 376 2.16 Example 144 Aldrich; or Baruah et al., 1999, 4, 409 Intermediate 33 386 2.59 Example 145 ch3 View ^^n, ch3 Aldrich Intermediate 33 375 1.73 Example 146 H3C\/CH3 M^&lt;CH3 Fluorochem Wesley Street Old Glossop Derbyshire SK13 7RY United Kingdom Intermediate 33 360 2.16 87841-960303-中.doc 217- 1283678 Example 147 —% Aldrich; or Acros; or Jung et al, Tetrahedron Lett., 2002, 43(48), 8735; Or Meindl et al, J. Med. Chem., 1984, 27(9), 1111; or Organic Lett,, 2002, 4(12), 2055 Intermediate 33 410 2.4 Example 148 Η Ό Berk Univar pic Ber k House POBox 56 Basing View Basingstoke Hants RG21 2E6, United Kingdom Intermediate 33 473 2.26 Example 149 Human CH3 Η 3 Aldrich Intermediate 33 375 1.9 Example 150 MicroChemistry-RadaPharma Shosse Entusiastov 56 Moscow, 111123 Russia Intermediate 33 411 1.95 Example 151 H3c Array Biopharma Inc. 1885 33rd Street Boulder, CO 80301 USA Intermediate 33 395 1.73 Example 152 If^ If Nippon Kagaku Zasshi.^ I960, 81 p.962. Intermediate 33 453 1.96 Example 153 Aldrich Intermediate 33 408 2.35 Example 154 F Aldrich Intermediate 33 416 2.5 Example 155 mJ〇^ Aldrich; or Meindl et al, J. Med. Chem., 1984, 27(9), 11Λ1; or Organic Letters, 2002, 4(12), 2055 Intermediate 33 448 2.68 218- 87841-960303-中.doc 1283678 Example 156 Guang 3 N, ^ch3 AlfaAesar, A Johnson Matthey Company 30 Bond Street Ward ΗιΙΙ, ΜΑ 01835-8099 USA Intermediate 33 360 2.16 Example 157 V Aldrich Intermediate 33 330 2.04 Example 158 〇-\^nh2 Aldrich Intermediate 33 347 1.83 Example 159 〇, ch3 Aldrich Intermediate 33 396 2.49 Example 160 HN\ F Aldrich Intermediate 33 4 16 2.53 Example 161 Aldrich Intermediate 33 390 2.18 Example 162 Aldrich Intermediate 33 463 1.96 Example 163 〇^ch3 US 4987132 Intermediate 33 458 2.13 Example 164 Aldrich Intermediate 33 374 2.22 Example 165 Aldrich; or TCI-America; or Maybridge- Int. Intermediate 33 406 2.53 Example 166 Maybridge Chemical Company Trevillett Tintagel Cornwall PL34 0HW United Kingdom Intermediate 33 402 1.93

87841-960303-中.doc -219-1283678 Example 167 HN^ φι. (iv) h3c/0 Aldrich; or Barnah et al., “/Price, 1999, 4, 409 Intermediate 33 440 2.3 Example 168 idN^ Aldrich; or Meindl et al., J. Med. Chem., 1984, 27(9) , 1111; or Organic Letters, 2002, 4(12), 2055 Intermediate 33 414 2.58 Example 169 〇Aldrich Intermediate 33 373 1.64 Example 170 -^-ΟΗ Aldrich Intermediate 33 334 1.85 Example 171 % h3c Aldrich Intermediate 33 465 2.29 Example 172 CH3 EP 666258 Intermediate 33 458 2.25 Example 173 ?η3 -^YN-ch3 J. Chem. Soc., 1954, 1171 Intermediate 33 389 1.98 Example 174 ΗΝ-^\ /CH3 Peakdale Corporation, Peakdale Science Park , Sheffield Road, Chapel-en-le-Frith, High Peak SK23 OPQ United Kingdom Intermediate 33 384 1.76 Example 175 Χλλ〇η3 οΛ〇Fluorochem Wesley Street Old Glossop Derbyshire SK13 7RY United Kingdom Intermediate 33 459 2.36 Example 176 Lancaster Synthesis Company, Newgate, White Lund, Morecambe, Lancashire LA3 3DY, United Kingdom Intermediate 33 343 2.01 Example 177 h3C\Ά〇η3 ChemBridge Europe, 4 Clark's Hill Rise, Hampton Wood, Evesham, Worcestershire WR11 6FW5 United 1 Kingdom Intermediate 33 400 1.92 87841-960303-中.doc -220- 1283678 Example 178 Λ Ν-Ν Nch3 TimTec PO Box 8941 Newark, DE, 19714-8941 USA Intermediate 33 384 2.03 Example 179 ch3 1CH NW^CH3 ChemBridge Europe, 4 Clark's Hill Rise, Hampton Wood, Evesham, Worcestershire WR11 6FW, United Kingdom Intermediate 33 398 1.70 Example 180 Aldrich Intermediate 33 400 2.41 Example 181 &quot;^aCI Aldrich Intermediate 33 428 2.61 Example 182 ^^6 Aldrich Intermediate 33 424 2.49 Example 167: Ν·{[3,4·Bis(methoxy)phenyl]methyl}ethylethyl-4-(tetrahydro-2H-pyran-4-yl) Amino)-1Η-pyrazolo[3,4_b]pyridine-5-formamide

In an alternative embodiment to the above examples 100-182, Example 167 can be made according to the following procedure: Intermediate 33 (0.498 g, 1.72 mmol), EDC (0.46 g, 2.41 mmol) A mixture of hydrazine (0. 278 g, 1.68 mmol) was stirred at room temperature for 0.25 hours. Add cucurbitamine (3,4-dimethoxybenzylamine, 0.31 ml, 2.05 mmol, available from Aldrich or 5^/hr, 1999, 4, 409) and continue stirring at room temperature 22 hour. The reaction mixture was partitioned between Et20 and water. To 87841-9603〇3·中.doc -221 - 1283678

Et: 2 water phase was taken in the next year' and the combined organic phases were washed with brine, dehydrated (MgS〇4), and evaporated in vacuo. The residue was purified by EtOAc (EtOAc) eluting eluting The material was further purified by SPE (SCX-2, 10 g) with methanol, then with ammonia (? 5 Μ) &gt; The gas, if, and the mixture were combined and evaporated in vacuo to give a white foam (0.633 g). LCMS showed MH+ = 440; Tret = 2.65 min. iH NMR (400MHz, in CDC13, 27°C, 5 ppm) 9·78 (d,1H) 8_37 (s,1H) 7.94 (s,1H) 6.94-6.82 (m,3H) 6.29 (br m,1H 4.56 (d,2H) 4.46 (q,2H) 4.15-4.01 (m,3H) 3.89 (s,6H) 3.63 (m,2H) 2.15 (m, 2H) 1.78 (m,2H) 1.49 (t,3H Example: 183: 4_(cyclohexylamino)-l-(3_ethoxy-3- ketopropyl-p-[3,4-b]pyridine-5-carboxylic acid ethyl ester

C〇2Et C〇2Et The mixture of intermediate 48 (40 mg), anhydrous potassium carbonate (57 mg) and ethyl bromopropionate (0.027 ml) in anhydrous DMF (1 mL) Heat at C overnight. The reaction mixture was concentrated, and the residue was partitioned between methylene chloride (5 liters) and water (5 ml). The liquid phase was separated and the organic phase was evaporated to a residual oil which was purified by preparative purification to give 183 (5 mg). LCMS showed mh+ = 389; T = 3 87841-960303 - medium .doc - 222 - 1283678 min. Example: 1-n-propyl-4-(tetrahydroendan-4-ylamino)-1Η_峨君[3,4-b]pyridine-5-carboxylic acid ethyl ester

Sodium hydride (0.067 g, 6% dispersion in oil) was added to a stirred solution of Example 20 (0.47 g) in DMF (19 mL), followed by i-propyl iodide: Μ〇·17 Pen rise). The mixture was shaken off for 1 hour, then concentrated, diluted with air (3 mL) and washed with a 1:1 water: brine solution (30 mL); The residue was purified on an arc cartridge (Ji, H), hexanes, m. The combined hydrazines: diethyl ether: cyclohexane and diethyl ether were separated from the mixture, and 4 was used in Example 185 as a clear gum (0.23 g). LCMS showed MH+ = 333; TRET = 3.14 min. ^ ^ lg6 · 1-(2_Ethyl)·4_(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine_5_carboxylic acid B Ester 87841·96〇3〇3·中.doc -223 - 1283678

2-Bromoethanol (0. 008 ml) and 2-tris-butylimido-2-diethylamino-1,3-monomethyl-β-hydrogen-1,3,2-diazo The phosphane (polymerized, 2.3 mmol/g loading &lt; 0 045 g) was added together to a solution of Example 20 (0.03 g) in dry DMF (15 mL). The mixture was shaken at 23 ° C for 16 hours, then the solution was allowed to dry from the resin, and the resin was washed with DMF. The combined organics were concentrated and the residue was purified on EtOAc EtOAc (EtOAc) The combined fractions were concentrated to give mp mp (m. LCMS showed]^+=335; Tret = 2.47 min. 3L Example 187_ : N_[4-(4-) Alkyl]_1_-n-propyl_4_(tetrahydro-2-indole·t-but-4-ylamino)-1Η_峨吐和[3,4- b]pyridine carbenamide

Intermediate 50 (0.03 g) was stirred in DMF (1 mL) with DIPEA (0.035 mL) &lt;RTI ID=0.0&gt;&gt;&gt; 4_(Methanesulfonyl)benzylamine hydrochloride (0.024 g) was added to the mixture, and the solution was stirred at 23 ° C for 8 hours. The solution was concentrated, and the residue was evaporated mjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjj The organic layer was concentrated to give 187 (m. LCMS showed MH+ = 472; Tret = 2.67 min. 188: N-(4-Fluorophenyl)-1-n-propyl (tetrahydro-2H-(pyridin-4-ylamino)- lH-Ptb s[3,4-b]p -S·Artemisamine

The synthesis was carried out as described in Example 187 except that 4-(methylsulfonyl)myramine hydrochloride was added and 4-fluoroaniline (0.01 mL) was added to the mixture. The product formed required further purification by mass-directed preparative HPLC to give Example 1S8 as a clear gum (0. 〇 3 g). LCMS showed MH+ = 398; Tret = 3.13 min. EXAMPLE 189: 1-Ethyl_6-methyl-4-(tetrahydro-2H-piperidin-4-ylamino)-iH-pyrazolo[3,4-b]pyridine-5.carboxylic acid Ethyl ester 87841-960303-中.doc -225-1283678 α

Add 4-aminotetrahydropyran hydrochloride (intermediate 8 Α, 0.413 g, 3.0 mmol) to intermediate 51 ((). 268 g, (d) Mo) and n, n-diisopropyl Ethylethylamine (0.87 ml 5.0 mmol) in a mixture of acetonitrile (3 mL). The &amp; formed material was heated at 85 C for 24 hours. The volatiles were removed in vacuo and the residue dissolved in chloroform (1. 5 mL) and applied to spE cartridge (5 g). The cartridge was continuously dissolved in % 〇, Et 〇 Ac and (9). The fractions containing the desired product are combined and concentrated in vacuo to give the desired material which is eluted from starting material (intermediate 51). Further purification was carried out using an SPE cartridge (yellow gel, 5 g), eluting with ethyl acetate-cyclohexane (1/3) to give the Example 189 (0.248 g). LCMS showed MH+ = 333; Tret = 2.75 min. Rabbit Example 190: 4-(cyclohexylamino)-1_ethyl-6-methyl-1H-pyrazolo[3,4-7]pyridine winter carboxylic acid ethyl ester

Add cyclohexylamine (O.H9 g '1.5 mmol) to Intermediate 51 (0.201 g, 87841_96〇3〇3·中.doc -226-1283678 〇·75 mmol) and N,N-II Isopropylethylamine (〇·65 ml, 3.73 mmol) in a mixture of acetonitrile (3 mL). The resulting mixture was heated at 8 yc for 40 hours. The volatiles were removed in vacuo and the residue was taken up in EtOAc (1 mL) and applied to a SpE cartridge (5 g of EtOAc, EtOAc and MeOH). The solute fractions were combined and concentrated in vacuo to give EtOAc (EtOAc: EtOAc). _Ν-[4-(Methanesulfonyl) aryl] Η Η-ρ than wow [3,4-b] outside 1; _____

A mixture of intermediate 52 (0.014 g, 0.046 mmol), HATU (0.018 g, 0.048 mmol) and DIPEA (0.022 mL, 0.125 mmol) in DMF (1 mL). 1 minute. Then (methanesulfonyl)phenyl]methylamine (0.009 g, 0.046 mmol) was added and the mixture was shaken for a few minutes to obtain a solution. This solution was stored at room temperature for 16 hours. The solution was concentrated in vacuo and the residue was taken in EtOAc (EtOAc)EtOAc. The cartridge was continuously dissolved in chloroform (1.5 mL), EtOAc (1.5 mL) and Et. The fractions containing the desired product were concentrated in vacuo to give Example 191 (5 g). 87841-960303-中.doc -227- 1283678 LCMS shows MH+=470; Tret=2.54 min. Example 192: N-benzyl-4-(cyclohexylamino)-1-ethyl-6-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide

Example 192 was prepared from Intermediate 52 using a procedure analogous to Example 191. LCMS showed MH+ = 392: Tret = 2.43. Example 193: 4-(cyclohexylamino)-1 ethyl hydrazide (4-fluorophenyl)·6-methyl-1H-pyrazolo[3,4_b Pyridine-5-carboxamide

Example 193 was prepared from Intermediate 52 using a procedure analogous to Example 191. LCMS showed MH+ = 396; Tret = 2.6 min. Example 194: 4-(cyclohexylamino)_1-ethyl-6-methyl-indole-[4.(trifluoromethyl)-yl-1H-pyrazolo[3,4-b]pyridine- 5-carbamamine 87841-960303-中.doc -228- 1283678

Example 194 was prepared from Intermediate 52 using a procedure analogous to Example 191. LCMS showed MH+ = 460; Tret = 2.74 min. Example 195: 4-(Cyclohexylamino)-N-(2,3-dihydro-1H-indol-2-yl)succinylethyl-6-fluorenyl-1H-pyrazolo[3,4-b] Pyridine _5·guanamine

Example 195 was prepared from Intermediate 52 using a procedure analogous to Example 191. LCMS showed MH+ = 418; Tret = 2.55 min. Example 196: N-Benzyl_1-ethyl-6-methyl-4-(tetrahydro-2H-piperidin-4-ylamino)_1H-pyrazolo[3,4-b]pyridine-5 -Procarbamide

Example 196 was prepared from Intermediate 53 using a procedure analogous to Example 191. 87841-96〇3〇3_中.doc -229- 1283678 LCMS shows MH+=394; Tret = 2.02 min. Example 197: N-benzylic small ethyl-4-[(2-keto-nitros-7-indole-3-yl)amino]-Twisted-pyrazolo[3,4-b]pyridine-5- Formamide

3-Amino-adenositane-2-one (0.043 g, 0.335 mmol, commercially available from Sigma-Aldrich) was added to Intermediate 17 (0.021 g, 〇·067 mmol) and DIPEA (0.058 mL, 0.335 mmol) in acetonitrile (0.5 mL). The resulting mixture was heated at 85 ° C for 48 hours. The volatiles were removed in vacuo and the residue was dissolved in chloroform (5 mL) and applied to &lt;&lt;&gt;&gt; 5 ml), ethyl acetate (1.5 ml) and ethyl acetate-methanol (9/1, 15 ml) were dissolved. The fractions containing the desired material were concentrated in vacuo to give Example 197_9:). LCMS showed MH+ = 407; Tret = 2.81 min. The following compounds were prepared in a similar manner. The oxime 1 replaced the 3-amino-naphthyl sulphonate with another amine, R3NH2, which is equivalent to a molar number:

87841-96〇3〇3-中·doc -230- 1283678 Example No. NHR3 Source of R3NH2 Starting material MH+ Ion Tret (minutes) Example 198 OH hn{5 J. Chem. Soc" Perkin Trans· 1, 1994, 537 Intermediate 17 394 2.75 Example 199 HN-/V-OH Aldrich; or TCI-America Intermediate 17 394 2.82 Example 200, ~cr0H US 4219660 Intermediate 17 380 2.70 Example 201: N-Benzyl-1_ethyl-4 -[(4-ketocyclohexyl)amino]-1H-pyrazolo[3,4·b]pyridine_5-formamide

Intermediate 54 (0.048 g, 0.32 mmol) was added to a mixture of intermediate 17 (0.050 g, 0.16 mmol) and DIPEA (0·17 mL, 0.98 mmol) in acetonitrile (3 mL) . The resulting mixture was heated under reflux. After 12 hours, another quantity of intermediate 54 (0.044 g, 0·29 mmol), DIPEA (0.17 mL 0.98 mmol) and acetonitrile (1 mL) were added to the reaction mixture and kept at reflux. under. After 36 hours, the reaction mixture was evaporated EtOAcjjjjjjjjj The organic solution was evaporated to give a viscous oil, which was taken in dichloromethane (2 mL) and applied to a SPE cartridge (5 g). The cartridge was continuously treated with ethyl acetate-cyclohexane gradient (1: 16, then 1:8, 1:87841-960303-medium.doc-231-1283678 4, 1 : 2, 1 : 1 and 1: 0 ) Dissolution. Example 201 (0.018 g) was obtained by concentrating the fractions containing the desired material in vacuo. LCMS showed MH+=392;

Tret = 2.95 minutes. Example 202: 1-ethyl(2-hydroxysodiummethylethyl)-4-(tetrahydro-211-pyran-4-ylamino)_1Η-pyrazolo[3,4-b]pyridine-5 _mercaptoamine

Intermediate 33 (0.1 g, 0.34 mmol), EDC (0.066 g, 0.34 mmol) and hydrazine (0.05 g, 0.37 mmol) were suspended in DMF (2 mL) at room temperature Stir under nitrogen for 15 minutes. 2-Aminopropanol (0.026 g, 〇·34 mmol) and triethylamine (0.036 g, 0.36 mmol) were added, and the mixture was stirred for 6 hours under warm nitrogen. The solvent was removed in vacuo and the residue was partitioned between DCM and water. The organic layer was concentrated and applied to a SPE cartridge (amine propyl, 5 g) which was eluted with methanol. Concentrate in vacuo to give Example 202 (0.095 g). LCMS showed] VlH+ = 348, TRET = 2.15 min. ^ 203 : (2S)-2-({[l-ethyl_4-(tetrahydro-2H_pyran-4-ylamino)-1Η-pyrazolo[3,4-b]v -5-基】谈基}Amino)_3·趣基丙酸甲酿-232- 87841_96〇3〇3·中 doc 1283678

X OH C02Me reaction pattern:

Co2h intermediate 33 H2N and C02Me hydrochloride

EDC, HOBT, Et3N, DMF

Intermediate 33 (0_1 g, 0.34 mmol), edc (0.066 g, 〇·34 mmol) and HOBT (0.05 g, 0·37 mmol) were suspended in DMF (2 mL) and A &amp; and nitrogen under the disturbance for 15 minutes. L-Amino acid methyl ester hydrochloride (0.054 g, 0.34 mmol) and triethylamine (36 g, 0.36 mmol) were added, and the mixture was stirred at room temperature under nitrogen for 18 hours. . The solvent was removed in vacuo and the residue was partitioned between DCM and water. The organic layer was concentrated in vacuo and applied to a sep. Concentration in vacuo gave an impure residue which was purified further eluted with EtOAc EtOAc (EtOAc) The desired fraction was concentrated in vacuo to give EtOAc (EtOAc: EtOAc). 1^^8 shows 丽+=393;!^ = 2.22 minutes. Example 204: Ethyl 1-ethyl-4-[(4-hydroxycyclohexyl)amino]-1Η-pyrazolo[3,4-b] 87841-960303-中 .doc -233 - 1283678 Pyridine-5 -carboxylic acid ethyl ester

Intermediate 1 (1.5 g, 5.9 mmol) was dissolved in acetonitrile (8 mL). Add trans-alurylcyclohexanol (〇817 g, 71 mmol, commercially available from America; or, for example, Ηα salt) from Aidrich) and diisopropylethylamine (6.18 liters) , 35.5 耄 Mo ear), and the mixture at 85. Stir under the arm for 16 hours. The mixture was concentrated in vacuo and the residue was crystallised between DCM (12 mL) and water (3 mL). The liquid phase was separated, and the organic phase was dried (Na.sub.2SO.sub.4) and evaporated to give a pale yellow solid. The solid was dissolved in a mixture of dcm (1 mL) and chloroform (3 mL) and applied in aliquots to two spE cartridges (tank, 20 g) successively in Et. Liquid (1: %, then 1 ·· 8, 1 · 4, 1 · 2, 1 · 1 and 1 : 〇) Dissolution. The dissolved fractions containing the desired material were combined and evaporated in vacuo to afford Example 2 4 (1 893 g) as a white solid. LCMS showed MH+ = 333; Tret = 2.79 min. Example 205: Ethyl [ethyl_4_[(4-ketocyclohexyl)amino]-1H-pyrazolo[3,4_b]pyridine_5·carboxylate

Example 204 (1.893 g, 5.7 mmol) was suspended in acetone (12 mL), and 87481_96〇3〇3·中.doc-234-1283678 at 〇C, with jones reagent (1·81 liters) The stirred suspension is treated. 3 minutes. Thereafter, another amount of J〇nes reagent (1.81 ml) was added to the reaction mixture to keep it at 0 C. After a further 2 hours, the last J〇nes test J (1.44 liters) was added to the reaction mixture and stirring was continued for an hour. Isopropanol (3.8 mL) was added to the reaction mixture followed by water (15 mL). The resulting mixture was extracted with ethyl oleate (2 x 40 mL). The combined organic extracts were washed with water (8 mL), dried and evaporated. The solid was dissolved in DCM (10 mL) and applied in aliquots to two SPE cartridges (a mixture of 20 g). : 8, 1 : 4, 1 : 2 and 1: 1) Dissolution. The fractions containing the desired material were combined and evaporated in vacuo to give EtOAc (m. LCMS showed MH+ = 331; T rt = 2.84 min. _Example 2〇7 : 4_[(1_Ethyl-4-pyridinyl)amino]_1_ethyl-1H-pyrazolo[3,4_b]p ratio bite-5-rebel B wine

Intermediate 1 (2.58 g), intermediate 6 (2.0 g) and N,N-diisopropylethylamine (8.9 ml) were dissolved in acetonitrile (98 ml). The reaction mixture was heated at 85 ° C for 24 hours, then another portion of intermediate 6 ((8 g) was added and heating was continued for a further 10 hours. The reaction was concentrated in vacuo and the residue was taken between DCM and water. The liquid phase was separated, and the liquid phase was separated, and the organic phase was evaporated in vacuo. The residue of 87841-960303-M.doc-235 - 1283678 was purified by chromatography using Biotage (90 g), DCM: Me〇 H (5%) was dissolved, and Example 207 (1.55 g) was obtained as a white solid. LCMS showed MH+ 360, Tret = 2.71 min. 1 209: 4-[(4-aminocyclohexyl)amino] Ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate

Example 209 was prepared from the intermediate 1 and (4-aminocyclohexyl)amine using a procedure analogous to that used for the preparation of Example 207. LCMS showed MH+ = 332; Tret = 2.18 min. Example 210: 1-ethyl-Ν·[(1_oxidation_3-pyridyl)methyl]·4_(tetrahydro-2H-pyran-4-ylamino)-1Η-pyrazolo[3, 4_b]pyridine_5_formamide

A solution of m-benzoic acid (45 mg, 〇·26 mmol) in chloroform (1 mL) was added dropwise to Example 138 (0.1 g, 〇·26 mmol) Ear) in a stirred solution in chloroform (1.5 ml). After 5 hours at 〇 °c, another amount of chloroperoxybenzoic acid (45 mg, 0.26 mmol) was added between chloroform (1 ml) and stirring was continued for 1.5 hours at 〇 ° C. . Residual trace 87841-960303-中.doc -236- !283678 Starting material, so add another amount in chloroform (0.6 ml) -chloroperoxybenzoic acid (22 mg, 0.13 mmol). After 3 hours at 0 ° C, 2 Μ of carbonic acid (1 ml) was added to the reaction mixture. The liquid phase was separated by passing through a hydrophobic glass and the aqueous phase was extracted with more chloroform (2 mL). The combined organic extracts were evaporated to a residual foam which was purified by preparative HPLC eluting with EtOAc. LCMS showed MH+ = 397; Tret = 2.13 min. Exception 211 : 1 ethyl-N-[(l_oxy-2-pyridyl)methyl]-4-(tetrahydro-2-indolyl-4-ylamino)-1Η-pyrazolo[3, 4-b]pyridine-5-carboxamide

Example 211 was prepared from Example 600 using a procedure similar to that used to prepare Example 210. LCMS showed MH+ = 397; Tret = 2.20 min. Example 212: 1-ethyl-N-[(l-oxidation_4·ρ ratio) methyl]-4-(tetrahydro-2H-succinylamine-based ratio [3,4_b]pyr ratio 5--5-armamamine

Example 212 was prepared from Example 33 using a procedure similar to that used to prepare Example 210. LCMS showed MH+ = 397; Tret = 2.13 min. 87841-960303-中.doc -237- 1283678 Examples 214 to 230

The general procedure is to use intermediate 17 (0.15 mmol) as one of the stock solutions from acetonitrile (〇.2M) and N,N-diisopropylethylamine (0.24 mmol). 95 ml, equivalent to 0.19 mmoles). The mixture was heated under reflux for 2 hrs and then quenched in a vacuum. The residue is purified by SPE (crushed) to obtain the desired product.

-238 - 87841-960303-中.doc 1283678 Example No. NHR3 R3 Source of NH2 Starting material MH Ten ion LC-MC Retention time 214 J. Med·Chem" 1994, 37(17), 2360 Intermediate 17 393 2.16 221 Force Mi Aldrich Intermediate 17 350 3.18 222 Aldrich Intermediate 17 392 3.62 223 H, exx Aldrich Intermediate 17 392 3.63, 3.68 224 Pfaltz-Bauer Intermediate 17 392 3.61, 3.66 225 J. Org. Chem., 1985, 50 ( 11), 1859 Intermediate 17 392 3.54 226 h6k Η, industry Aldrich Intermediate 17 390 3.56 227 h Aldrich Intermediate 17 390 3.52 228 0 WO 99/12933 Intermediate 17 379 2.66 229 0 EP 1188744 Intermediate 17 393 2.58 230 mhQJ Aldrich Intermediate 17 405 2.19 Example 225: 1-Ethyl-4-[(l-methylcyclohexyl)amine]·Ν·(phenylmethyl)-1Η-pyrazolo[3,4-b Pyridine-5_guanamine

-239 87841-96〇3〇3-中.doc 1283678 A preferred method for the preparation of Example 225 and involving 1-methylcyclohexylamine with a longer reaction time is as follows: stirring intermediate 17 (46 mg), A solution of μmethylcyclohexylamine (26 mg) and diisopropylethylamine (94 mg) in acetonitrile (m. More 丨-methylcyclohexylamine (1 〇 2 mg), diisopropylethylamine (93 mg) and acetonitrile (m) were added, and the reaction mixture was heated under reflux for a further 68 hours. The solution was allowed to cool and concentrated in vacuo. The residue was triturated in acetic acid and filtered. The filtrate was purified by preparative HPLC by mass guidance to give Example 225 (19 mg). LCMS showed MH+ = 392; Tret = 3.46 min. Examples 231, 247 and 257, which are not hereinafter and also involve 1-methylcyclohexylamine, may also preferably be made in a similar manner. Example 231_239

The general procedure is to use the intermediate 55 (0.15 mmol) as one of the stock solutions from acetonitrile (〇·2Μ) and N,N-diisopropylethylamine (0.24 mmol). 95 ml, equivalent to 0. 19 millimoles). The mixture was heated under reflux for 2 () hours and then concentrated in vacuo. The residue was purified by SPE (Silver) to obtain the desired 嶋-960303-中.doc-Qin 1283678 Example No. NHRJ R3 ΝΗ2 Source of starting material MH Ten ion LC-MC Retention time 231 J. Org, Chem" 1985, 50(11), 1859 Intermediate 55 422 3.43 233 Aldrich Intermediate 55 380 3.20 234 Aldrich Intermediate 55 422 3.58 235 | Η This Aldrich Intermediate 55 420 3.52 236 Aldrich Intermediate 55 422 3.57, 3.64 ΊΠ Pfaltz-Bauer Intermediate 55 422 3.56, 3.62 238 Η~ Aldrich Intermediate 55 420 3.48 239 J. Med. Chem.y 1994, 37(17), 2360 Intermediate 55 423 2.16 Example 240-249

NHS02Me General procedure Intermediates 56 (0.15 mmol) are obtained as a liquid amine from one of the stock solutions of acetonitrile (0.2 M) and N,N-diisopropylethylamine (0.24 mmol). 0.95 ml, equivalent to 0.19 millimoles). The mixture was heated under reflux for 20 hours and then concentrated in vacuo. The residue is purified by SPE (crushed) to obtain the desired product. -241 - 87841-960303-中.doc 1283678 Example number NHR' R3 ΝΗ2 Source Starting material MH + ion LC-MC Retention time 240 乂) Aldrich Intermediate 56 485 3.26 241 X7 m Aldrich Intermediate 56 443 2.94 242 Η Aldrich Intermediate 56 483 3.20 243 H Aldrich Intermediate 56 483 3.14 244 Ά Aldrich Intermediate 56 485 3.25,3,33 245 Pfatlz-Bauer Intermediate 56 485 3.24,3.31 247 J. Org. Chem,, 1985, 50(11), 1859 Intermediate 56 483 3.10 248 J. Med, Chem.y 1994, 37(17), 2360 Intermediate 56 486 2.05 249 cx Aldrich t-space 56 471 .3.21 Example 250-258

The general procedure is to use intermediate 57 (0.15 mmol) as one of the stock solutions from acetonitrile (0.2 M) and N,N-diisopropylethylamine (〇·24 mmol). (0.95 ml, equivalent -242- 87841-960303-medium.doc 1283678 at 0.19 mmol). The mixture was heated under reflux for 20 hours and then concentrated in vacuo. The residue is purified by SPE (gelatin) to obtain the desired product. Example No. NHR3 R3 NH2 Source Starting material MH ion LC-MC Retention time 250 Aldrich Intermediate 57 418 3.78 251 Aldrich Intermediate 57 376 3.42 253 Pfaltz-Bauer Intermediate 57 418 3.78, 3.84 254 Aldrich Intermediate 57 418 3.82, 3.86 255 Η Aldrich Intermediate 57 416 3.66 256 H &quot;tJtl Aldrich Intermediate 57 416 3.77 257 J, Org, Chem,, 1985, 50(11), 1859 Intermediate 57 418 3.74 258 H, Nv^ i J. Med. Chem.y 1994, 37(17), 2360 Intermediate 57 419 2.38 Examples 259-275

General Procedure A mixture of intermediate 58 (0.1 mmol), HATU (0.1 mmol) and DIPEA (0.4 mmol) in DMF (0.4 mL) was shaken for 10 min. Then -243 - 87841-960303-中.doc 1283678 A solution of the amine (0.1 mole) in DMF (0.2 mL) was added and the mixture was stirred for a few minutes to give a solution. The solution was stored at room temperature for 16 hours and then concentrated in vacuo. The residue was dissolved in chloroform (0.5 mL) and applied to a &lt;&gt;&gt;&gt;E cartridge (aminopropyl, 0.5 g). The cartridge was lysed in chloroform (1.5 mL), EtOAc (1.5 mL) and EtOAc:EtOAc (EtOAc (EtOAc) The fractions containing the desired product were concentrated in vacuo and the residue was purified by preparative HPLC with mass. Example No. NR4^ r3nh2 Source Starting material MH + ion LC-MC Retention time 201 Aldrich Intermediate 58 392 2.60 259 EP 666258 Intermediate 58 470 2.44 260 Salor; or ICN Biopharmaceutical Company; or Synthesis f 1982, 12, 1036 Intermediate 58 420 3.09 261 CHMSRV-AS; or Matrix Science; or Chem. Ber., 1969, 102, 2770 Intermediate 58 420 3.09 244- 87841_96〇3〇3·中.doc 1283678 262 Aldrich; or Meindl et al, /· Med, Chem·, 1984, 27(9), 1111. Intermediate 58 454 3.20 263 CH, Acros; or Aldrich; Tetrahedron Lett., 2002, 43(48), 8735; or J. Med. Chem., 1984, 27(9), 1111; or Org. Lett., 2002, 4(12), 2055 Intermediate 58 422 2.86 264 Lis ¥ Person, J. Med. Chem., 1990, 33(10), 900a. See h formula 111 and reference 24 Intermediate 58 485 2.64 265 1 Aldrich Intermediate 58 435 2.54 266 Fluorochem; or WO 98/45268 Intermediate 58 458 2.81 267 Aldrich; or Meindl et al, / Med, Chem" 1984, 27 (9), 1111; or Org. Lett, 2002, 4(12), 2055 Intermediate 58 460 2,96 268 &quot;-of Peakdale Intermediate 58 470 2.39 269 Aldrich Medium Interstitial 58 396 2.80 270 (for cf3 co2h salt) Aldrich Intermediate 58 393 1.89 271 TCI-America; or Aldrich; or Maybridge-Int Intermediate 58 418 2.77 272 WO 99/38877 Intermediate 58 427 2.13 87841-960303· .doc 245 - 1283678 273 \^N ND Zelinsky Society Intermediate 58 396 2.15 274 Aldrich Intermediate 58 330 2.10 275 Matrix Scientific Intermediate 58 399 2.29 Example 276-287

General Procedure A mixture of intermediate 59 (0.1 mmol), HATU (0.1 mmol) and DIPEA (0.4 mmol) in DMF (0.4 mL) was shaken at room temperature for 10 min. A solution of the amine (0.1 mmol) in DMF (0.2 mL) was then added and the mixture was stirred for a few minutes to give a solution. The solution was stored at room temperature for 16 hours and then concentrated in vacuo. The residue was dissolved in chloroform (0.5 mL) and applied to EtOAc (EtOAc: The cartridge was continuously dissolved in chloroform (1.5 mL), EtOAc (1.5 mL) and EtOAc······· The fractions containing the desired product were concentrated in vacuo and the residue was purified by preparative HPLC with mass. 87841-960303·中.doc -246-1283678 Example Number NR4R' hnr4r5 Source Starting Material MH+ Ion LC-MC Retention Time 276 Aldrich Intermediate 59 392 2.60 277 F Fluorochem; or WO 98/45268 Intermediate 59 446 2.84 278 Aldrich; or Meindl et al, J. Med. Chem., 1984, 27(9), 1111; or Og. Lett,, 2002, 4(12), 2055 Intermediate 59 448 3.0 279 Acros Intermediate 59 458 2.40 * 280 EP 382570 Intermediate 59 458 2.47 1 ii 281 Aldrich Intermediate 59 384 2.85 282 (for cf3 co2h salt) Aldrich Intermediate 59 381 1.89 jii 1 283 TCI-America; or Aldrich; or Maybridge-Int Intermediate 59 406 2.80 1 1 284 WO 99/38877 Intermediate 59 415 2.14 285 \s^N ND Zelinsky Society Intermediate 59 384 2.16 286 Aldrich Intermediate 59 318 2.11 287 %:] Matrix Science · Intermediate 59 399 2.29 Case 288 : 4-[ (4,4-Difluorocyclohexyl)amino] _1 </ RTI> ethyl-indole (phenylphenyl)-1 hydrazinopyrazolo[3,4-b]pyridine-5-carboxamide and Example 289: 1-ethyl-4-[(4-fluoro-3-cyclohexan-1-yl)amino]-indole-(phenylmethyl)-1Η-pyrazolo[3,4-b]pyridine -5-carbamamine-247- 8784 1-960303-中.doc 1283678

Example 289 Add isopropylethylamine (〇·113 ml, 〇·65 mmol) to Intermediate 7 (40 gram, 〇j3 mp) and intermediate illusion (4) mM, 〇·26 毫Mohr) is stirred in a mixture of B (2 pens). At 85. The mixture was stirred under the arm. After 18 hours, add another intermediate 63 (22.5 mg, 0·13 mmol) to diisopropylethylamine (0.113 mL, 〇·65 mmol) to the reaction mixture and at 90 C Stirring was continued for 24 hours. The mixture was then concentrated in vacuo and the residue was crystallised eluted eluted eluted The liquid phase was separated and the aqueous phase was extracted with additional DCM (10 mL). The combined organic extracts were dried (Na2SO4) and evaporated in vacuo to afford a brown oil (65 mg) which was partially purified on a SPE cartridge (yel. Petroleum ether (1:8; 1 ·· 4 ; 1 : 2 ; 1 : 1 and 1: 0) is dissolved. Example 288 (19 mg) was obtained as a white foam (LCMS: MH+ = 414; TRET = 3.24 min) and Example 2 δ 9 by mass separation of two portions of pale brown oil (34 mg). (9 mg) as a white solid (LCMS: MH+= 394; Example 290-319 87841-960303-中.doc -248 - 1283678

Nr4r5 General Procedure A mixture of intermediate 60 (0.1 mmol), HATU (0.1 mmol) and DIPEA (0.4 mmol) in DMF (0.4 mL) was shaken at room temperature for 10 min. Then a solution of the amine (0.1 mmol) in DMF (0.2 mL) was added and the mixture was stirred for a few minutes to give a solution. The solution was stored at room temperature for 16 hours and then concentrated in vacuo. The residue was dissolved in chloroform (0.5 mL) and applied to EtOAc (EtOAc: The cartridge was lysed in chloroform (1.5 mL), EtOAc (1.5 mL) andEtOAcEtOAcEtOAc The fractions containing the desired product were concentrated in vacuo and the residue was purified by preparative HPLC with mass. Example number nr4r&quot; hnr4r5 source starting material MH+ ion LC-MC retention time 290 Aldrich; or TCI-America; or Maybridge-Int intermediate 60 447 2.96 291 Aldrich; or Meindl et al, / Med. Chem. 9 1984, 27(9), 1111. Intermediate 60 488/490 3.16 292 Aldrich; or Meindl et al, / Med, Chem.y 1984, 27(9), 1111; or Org· Lett, 2002, 4(12), 2055 Intermediate 60 439 2.84 -249- 87841-960303-中.doc 1283678 293 Aldrich Intermediate 60 457 2.92 294 F Aldrich Intermediate 60 457 2.87 295 Aldrich; or Meindl et al., 乂 Med. Chem., 1984, 27 (9 ), 1111. Intermediate 60 489 3.06 296 Aldrich; or Meindl et al., 乂 Med. Chem., 1984, 27(9), 1111; or inhibit. Lett., 2002, 4(12), 2055 Intermediate 60 489 3.08 297 / Aldrich Intermediate 60 457 2.82 298 Aldrich; or Meindl et al, */· Med. Chem.t 1984, 27(9), 1111; or Lett., 2002, 4(12), 2055 Intermediate 60 455 2.98 299 Aldrich; or Acros; or Jung et al., Tetrahedron Lett., 2002, 43(48), 8735; or Meindl et al, / Med, Chem., 1984, 27(9), 1111; or Org· Lett, , 20 02, 4(12), 2055 Intermediate 60 451 2.79 300 m^Qr' Aldrich Intermediate 60 437 2,82 301 Peakdale Molecular Company Intermediate 60 528 2.76 302 NH C0 Aldrich Intermediate 60 461 3.00 303 Peakdale Molecular Company Intermediate 60 464 2.31 -250- 87841-960303-中.doc 1283678 •304 Cl Aldrich; or Meindl et al, J. Med. Chem., 1984, 27(9), 1111. Intermediate 60 489 3.16 305 F Aldrich; or Og. Lett., 2002, 4(12), 2055 Intermediate 60 439 2.84 306 F Fluka Intermediate 60 473 2,92 307 Fluorochem Company; or WO 98/45268 Intermediate 60 487 2.95 308 W. , Apin Intermediate 60 485 2,94 309 Key There is a k company intermediate 60 456 2.65 310 -or J, Med. Chern., 2001,44(26), 4628 Intermediate 60 481 3.16 311 Manchester Organic Company "Intermediate 60 428 2.28 312 &quot;-OF Acres Chimica. Intermediate 60 499 2.37 313 Aldrich Intermediate 60 511 3.18 314 Lis. et al., «/· Med. Chem.y 1990, 33(10), 9〇Q*3 See 'Form III and Reference 24 Intermediate 60 514 2.60 315 WO 94/17035 Intermediate 60 478 2.47 316 ^ζ: 0 Sigma Intermediate 60 500 2.50 317 Peakdale Molecular Company Intermediate 60 478 2.49 -251- 87841- 960303-中.doc 1283678 318 WO 02/85860 Intermediate 60 464 2.42 319 1 Syngene Intermediate 60 452 2.45 Rabbit Example 320 1_Ethyl_N-4_hexahydropyridyl Winter (tetrahydro-2H-pyranose _ 4_ylamino)-iH_pyrazolo[3,4-b]pyridine_5-formamide

A solution of hydrogen chloride in dioxane (30 mL, 4 M, 0.12 mol) was added to a suspension of Example 126 (1.3 g, 2.75 mmol) in dioxane (10 mL) and The mixture was stirred at room temperature for 6 hours. The reaction mixture was allowed to stand for 14 hours, then the solution was evaporated and then azeotroped with DCm to afford a white solid. The solid was suspended in ethyl acetate (5 mL) and washed with sodium hydroxide (2N, 50 mL). The organic layer was dried with EtOAc (EtOAc m. LCMS showed MH+ = 373; Tret = 1.89 min. f Example 3211_ethyl with (4-hexahydropyridylmethyl)-4-(tetrahydro-2Εμ trace 4-ylamino)_1Η-ρ ratio and [3,4-b]峨- 5_甲甲胺

87841_96〇303_中.doc •252- 1283678 A solution of hydrogen chloride in dioxane (30 ml, 4M, 012 mol) was added to intermediate 72 (1.2, 2.5 mol) in dioxane (10 ml) The suspension was placed in the mixture and the mixture was stirred at room temperature for 6 hours. The reaction mixture was allowed to stand for 14 hours, then the solution was evaporated and evaporated to dryness with DCM to give a white solid (1·24 g). A portion of the solid (68 mg) was suspended in ethyl acetate and washed with a 2? sodium hydroxide solution. The organic layer was dried with EtOAc EtOAc (EtOAc) [CMS shows MH+=387; Tret=1.92 minutes. jT Example 322 1-Ethyl-N-[l_(ethyl continuation)_4_hexahydrou-pyrylate] _4_(tetrahydro-2jj&lt; __4_ylamino)-1Η-pyridin[ 3,4-b]pyramidine-5-formamide

Triethylamine (0.023 mL, 0.16 mmol) was added to a solution of Example 320 (0.043 g, EtOAc) The mixture was allowed to cool (ice/water bath over 10 min) and chlorobenzene (0.014 mL, 0138 m. The resulting solution was stirred at room temperature for 18 hours and then the solvent was removed with nitrogen vapor. The residue was dissolved in dichloromethane (1. 5 mL) and EtOAc (EtOAc) The organic layer was separated and sparged with nitrogen and applied to a SPE cartridge (2 g), eluting with 60% to 100% ethyl acetate in cyclohexane. The desired fractions were concentrated in vacuo to afford EtOAc EtOAc (EtOAc: LCMS showed MH+ = 465; T rt = 2.52 min. The following are made in a similar manner. 87841-960303-中.doc -253 - 1283678

Example No. NR'R' Source of sulfonated sulfonated sulfonium MH+ ion LC-MC Retention time 323 々, 々α A Aldrich 479 2.58 324 J. Org. Chem.y 1952,17, 1529 505 2.75 325 H3C, // rcx H3C //° 〇々,α Aldrich 451 2.41 •326 〇o ,cx 9 Aldrich 527 2.90 327 0. y0 σ&lt;α Aldrich 513 2.66 328 Η,Ο-Χ Aldrich 479 2.42

Example 329 N-丨1-(cyclopropylcarbonyl)_4_hexahydroindenyl] small ethyl winter (tetrahydroanthracene-pyro- 4-ylamino)-1Η-pyrazolo[3,4 -b]pyridine-5-carbamamine

Cyclopropanecarboxylic acid (0.011 ml, 0.138 mmol), EDC (0.031 g, 0.161 mmol) and HOBT (0.019 g, 0.138 mmol) were suspended in DMF (2 mM -254 - 87841-960303- Medium .doc 1283678 liters) and stirred at room temperature for 1 hour. Example 320 (0 043 g, 0.115 mmol) was added and the mixture was stirred at room temperature for 16 h. Most of the solvent was removed using a stream of nitrogen and the residue was partitioned between DCM (3 mL) and water (3 mL). The organic layer was blown down with nitrogen and applied to an SPE cartridge (aminopropyl, 1 g) which was dissolved in methanol. Concentration by nitrogen downwards to give an impure residue which was further purified by a SPE cartridge (cluster, 1 g) eluting with 50-100% EtOAc in cyclohexane followed by 5% MeOH in EtOAc. . The desired fractions were concentrated in vacuo to give a crystallite. LCMS showed MH+ = 441; Tret = 2.23 min. In a similar manner, the same or similar molar number of reagents and solvent volumes were used, and Example 320 was used as the starting material to make Examples 330 to 343, but using Example 321 (similar to the molar number) instead of Example 320 as the starting material. To carry out Examples 344 to 349, the following materials were prepared: 87841-96〇3〇3·中.doc 255- 1283678

Example No. NR4R&quot; Source of Carboxylic Acid MH+ Ion LC-MC Retention Time 330 Cr^〇H Aldrich 467 2.50 331 Aldrich 471 2.73 332, ch3 Aldrich 471 2.72 333 oa^ ολ0Η Aldrich 483 2.81 334 Ία HjCY^oh CH, Aldrich 443 2.27 335 οΛχ cA Combi-Blocks 485 2.17 336 Aldrich 429 2.38 337 Η·ναα 丫 丫. « Aldrich 472 2.20 338 °Λχ Oa. Synchem OHG 500 1.91 339 #cx Xt^ J. Med. Chem., 1998,41(5), 760 497 2.17 87841-960303-中.doc -256- 1283678 340 0 people Chemical structural units 498 1.94 341 H^C Interchim Intermediate 498 2.07 342 〇0^°« DE 3618135 471 2.33 343 Aldrich 509 2.75 344 Pull IH, c4^〇H Aldrich 485 2.78 345 m 〇a0H Aldrich 497 2.85 346 /CUm Λ Aldrich 455 2.50 347 〇x/w J. Med. Chem.y 1998,41(5), 760 511 2.42 348 mi X)UL Aldrich 523 2.78 349 Vcu H,CH,C Interchim Intermediate 512 2.29

Example 350 3-丨(1•Ethyl_5-{[(phenylmethyl)amino]carbonyl}_1H-pyrazolo[3,4-b]pyridin-4-yl)amino]cyclohexane Methyl carboxylate

Example 350 was prepared from Intermediate 17, and a method similar to that used in Preparation Example 207 -257- 87841-960303-.doc 1283678 was used. LCMS showed MH+=436; Tret=3.20. Recombination 1^1&gt;[(1-ethyl-5-{[(phenylmethyl)amino]carbonyl}-1Η-pyrazolo[3,4-b Pyridine-4-yl)amino]cyclohexanecarboxylic acid

A 2M solution of sodium hydroxide (0.5 mL) was added to a stirred mixture of EtOAc (EtOAc &lt;RTI ID=0.0&gt;&gt; After stirring at room temperature overnight, the reaction solution was concentrated, diluted with water (3 ml) and acidified with 2? The precipitate formed was collected by filtration, washed with water and dried to give s. LCMS showed MH+ = 422; Tret = 2.95 min. Example 352: ^Ethyl_N_(phenylmethyl)-4-(4-hexahydropyridylamino)-1Η-pyrazole and [3,4_bp ratio biting_5·carbamidine

Hydrochloric acid aqueous solution (20 mL, 5 M) was added to a solution of intermediate 65 (2.58 g, 5.40 <RTIgt; The reaction mixture was stirred at 20 C for 22 h then evaporated in vacuo. The residue was subjected to liquid separation between DCM and water &lt; The aqueous phase was basified with aqueous sodium hydroxide (2M) and extracted with EtOAc &lt;RTI ID=0.0&gt;&gt; The organic phase was evaporated <RTI ID=0.0> LCMS showed MH+ = 379; Tret = 2.1 〇 min.娃: H base bucket...heptamethoxy)ethinyl]_4_hexahydropyridyl}amino)-1H-pyrazolo[3,4b]pyridine-5-carboxylic acid ethyl ester

Add methoxyethyl hydrazine chloride (0.016 mg, OJ 44 mmol) and triethylamine (002 Mohr '0·144 mmol) to Example 352 in Reactivial (〇〇46 g, 0.122 VOM) ) in solution in DCM. The reaction was stirred at 2 ° C for 22 h then diluted with DCM and washed with aqueous NaHCI. The organic phase was separated and applied directly to the SPE cartridge (2 g of silicone). The cartridge was dissolved in DCM: MeOH (1% EtOAc) LCMS showed MH+ = 451; Tret = 2.66 min. Yi J 354 : Μ 1-methylethyl) tetrahydro JH-t-indoleylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester

Made in a similar manner to Example 186, using Example 2 (〇〇3 g, 〇1 mmol) with 2-bromopropane (1 〇 microliter, 〇11 mmol), after 16 hours, add another 87841 -960303-中.doc -259- 1283678 0·11 millimolar alkylating agent. The final compound formed was a clear gum (16 mg). LCMS showed MH+ = 333; Tret = 3.16 min. Example 355: 4-(cyclohexylamino)-1 -ethylmethyl-1H-pyrazolo[3,4-b]pyridine_5-carbamimidamine

Intermediate 64 (0.02 g, 0.084 mmol) and diisopropylethylamine (44 ml, 0.252 mmol) were suspended in N-methyltetrahydropyrrolidone (1 mL) and added. Hexylamine (0.012 ml, 0.1 mmol). The mixture was heated at 85 ° C and stirred in a ReactivialTM for 8 hours then concentrated in vacuo. The residue was partitioned between DCM (2 mL) and water (2 mL). The liquid layer was separated and the organic layer was concentrated <RTI ID=0.0></RTI> to <RTI ID=0.0> LCMS showed MH+ = 302;

Tret = 2.85 minutes. Example 3. Example 3. Ethyl-indole (4-fluorophenyl)-6-methyl_4_(tetrahydroindole-pyran-4-ylamino)-1Η-pyrazolo[3 ,4-b]pyridine-5-carboxamide

Example 356 was prepared using a method analogous to Example 191 from % of intermediate. LCMS showed MH+ = 398; Tret = 2.18 min. 87841-960303-中.doc -260-1283678 t·Example 357 : 1-ethyl-6-methyl-N-{[4-(methylsulfonyl)phenyl]methylhydrazine ice (tetranitro 2H_ Piperidine_4_ylamino)_1H_pyrazolo[3,4-b]pyridine-5-cartoamine

Example 3S7 was prepared using a method similar to that of Example 191 from % of intermediate. LCMS showed MH+ = 472; Tret = 2.15 min. Example 358: Team (2,3-dihydrol-based H_ethylmethylmethyl_4_(tetrahydro-2H-pyran-4-ylamino)-1H_p ratio and [3,4-7]峨淀-5_甲甲胺

Example 35δ was prepared using a method analogous to Example 191 from % of intermediate. LCMS showed MH+ = 394; Tret = 2.04 min. Call example 360-414

Nr4r5 General procedure Intermediate 33 (1 89 g) was treated with sulfinium dichloride (10 * liter) and the mixture of 87841·96 〇 3 〇 3 _ .doc - 261 - 1283 678 was heated under reflux for 2 hours. Excess ruthenium dichloride was removed in vacuo to give intermediate 73, which was assumed to be the ruthenium chloride of intermediate 33, which was a cream solid. The solid was suspended in tetrahydrofuran (32.5 ml) and a portion of the suspension was added to the amine (0.11 mmol) and N,N-diisopropylethylamine (0.165-0.22 mmol) in THF (0.5 ml In the mixture. The reaction mixture was stirred for 24 hours and the solvent was removed in vacuo. The residue was purified by preparative HPLC by mass guidance. Example No. NR4R^ hnr4r5 Source Starting material MH+ Ion LC-MC Retention time 360 ΟγΟ. Interchim Intermediate Intermediate 33 477 2.98 361 MU Aldrich Intermediate 33 408 3.45 362 α: Aldrich Intermediate 33 384 3.09 363 0 Butt Park Company Intermediate 33 437 2.69 364 丫χχ Aldrich Intermediate 33 432 3.21 365 Maybridge Chemical Company Intermediate 33 437 2.72 366 Aldrich Intermediate 33 382 2.67 367 f Interchim Intermediate Intermediate 33 519 3.01 368 Aldrich + Interstitial 33 367 2.19 369 Butt Park company intermediate 33 492 2.21 370. Heart J. Chem, Soc. C, 1969, 1444 Intermediate 33 449 2.72 87841-960303-中.doc -262- 1283678 371 Peakdale Technology Co., Ltd. 中间 Intermediate 33 444 2.81 372 VX J. Heterocycl Chem., 1975, 12 (2), 225 Intermediate 33 437 2.74 373. 'Interchim Intermediate Intermediate 33 459 2.79 374 Xx: Apollo Scientific Company Intermediate 33 400 2.99 375 a Aldrich Intermediate 33 400 3.35 376 6r Lancaster Intermediate 33 425 3.07 377 Maybridge CombiChem Intermediate 33 513 3.33 379 T° Peakdale Technology Limited Company Intermediate 33 444 2.99 380 〇丫N, J. Heterocycl. Chem” 1975, 12(2), 225 Intermediate 33 437 2.64 381 ΟγΟ-MU Interchim Intermediate Intermediate 33 479 2.68 382 Aceto Intermediate 33 425 3.38 383 Aldrich Intermediate 33 382 2.78 384 Aldrich Intermediate 33 400 3.38

87841-960303-中.doc -263 - 1283678 •386 丫0 HN, WO 03/32986 Intermediate 33 467 2,65 387 Ο, / Maybridge Chemical Company Intermediate 33 513 3.35 388 Intermediate 67 Intermediate 33 505 3.23 389 0 Lancaster Intermediate 33 451 3.17 390 EP 538945 Intermediate 33 487 2.80 391 Aldrich Intermediate 33 416 2.99 392 Interchim Intermediate Intermediate 33 459 2.74 393 Butt Park Company Intermediate 33 423 2.66 394 r F Aldrich Intermediate 33 434 3.43 395 N^nh Aldrich Intermediate 33 367 2.40 396 Aldrich; or Reetz, Synthesis^ 1999, 9, 1555 Intermediate 33 434 3,67 397 Η,-Lo Bayer AG Intermediate 33 479 2.89 398 η Explore Library Intermediate 33 451 2.91 399 ο./ Maybridge Chemical Company Intermediate 33 515 3.02

87841-960303-中.doc -264-1283678 400 9- 0 TimTec Intermediate 33 492 2.20 401 Exploring the library intermediate 33 437 2.68 402 α Lancaster Intermediate 33 468 3.53 403 0丄NH 〇1 Heterocycles, 1983 20(3 ), 445 Intermediate 33 437 2.70 404 α: Aldrich Intermediate 33 400 3.09 405 &amp; Aldrich Intermediate 33 418 3.21 406 Aldrich Intermediate 33 384 3.19 407 ά: Aldrich Intermediate 33 409 2.95 408 Helv, Chim. Actay 1983 66 (4), 1046 Intermediate 33 472 3.07 409 Αχ Butt Park Company Intermediate 33 437 2.68 411 VCH* Salor Intermediate 33 444 2.69 413 Peakdale Molecular Co., Ltd. Intermediate 33 437 2.35

Example 414: 1-Ethyl-4-(tetrahydro-2H-piperidin-3-ylamino)-1Η^ than spit [3,4-b]bambob-5-carboxamide-265 - 87841-960303-中.doc 1283678

The nh2 instance 414 was prepared from the intermediate 59 using the general method described in relation to the example 360-413 method. LCMS showed MH+ = 398; Tret = 2.90 min. Example 415-487

General Procedure A mixture of intermediate 61 (0.1 mmol), HATU (0.1 mmol) and DIPEA (0.4 mmol) in DMF (0.4 mL) was shaken at room temperature for 10 min. Then, a solution of an amine (〇·1 mmol) in DMF (0.2 ml) was added, and the mixture was stirred for several minutes to obtain a solution. The solution was stored at room temperature for 16 hours and then concentrated in vacuo. The residue was dissolved in chloroform (0.5 mL) and applied to EtOAc (EtOAc: The cartridge was lysed in chloroform (1.5 mL), EtOAc (1.5 mL) and EtOAc: MeOH (9:1, 1.5 mL). The fractions containing the desired product were concentrated in vacuo and the residue was purified by preparative HPLC with mass. Example No. nr4r5 Source of hnr4r5 Starting material MH+ Ion LC-MC Retention time 415 h2n 々〇 Rare chemical GmbH Intermediate 61 395 2.80 416 Aldrich Intermediate 61 345 2.64 4Π 0 Ultrafine (UFC) Intermediate 61 409 2.84 87841- 960303-中.doc -266- 1283678 418 Intermediate 8Α; or Intermediate 8 (Combi-Blocks) Intermediate 61 372 3.03 419 -CTm ND Zelinsky Society of Organic Chemistry 61 382 2.96 420 Peakdale Molecular Company Intermediate 61 456 3.22 421 Peakdale Molecular Company Intermediate 61 421 3.03 422 ζ-j^m Aldrich Intermediate 61 372 3.09 423 J. Org. Chem.y 1955, 20,1657 Intermediate 61 485 3.44 424 Key Organics Intermediate 61 413 3.39 425 ^ ^S02Me Acros Intermediate 61 456 3.19 426 OMe WO 00/17163 Intermediate 61 409 3,3 427 0 Peakdale Molecular Company Intermediate 61 421 3.23 428 Off · Peakdale Molecular Company Intermediate 61 435 3-07 429 0 Peakdale Molecular Company Middle Object 61 421 2.97 430 woven Apin intermediate 61 394 3.25 431 Acros; or Aldrich; or Jung et al, Tetrahedron Lett., 2002, 43(48), 8735; or Meindl . Al., J Fine Chem, 1984, 27 (9), 1111;. Or Org, Lett "2002, 4,2055 Intermediate 61 408 3.51

87841-960303-中.doc 267- 1283678 432 -xc; Aldrich Intermediate 61 414 3.68 433 De 5 Aldrich; A Meindl et al, / Med. Chem.t 1984, 27(9), 1111. Intermediate 61 446 3.81 434 J. Med. Chem.y 1999, 42(14), 2504 Intermediate 61 471 3.23 435 F Aldrich Intermediate 61 414 3.66 436 JX&quot;Aldrich; or Organic Letters, 2002, 4(12), 2055 Intermediate 61 392 3.69 438 Key Organics Intermediate 61 485 3.25 439 Buttpark Intermediate 61 394 3.52 440 ΙίΧ- Aldrich; or Meindl et al., Med. Chern., 1984, 27(9), 1111· Intermediate 61 446 4 441 aXpr^ Cl Lancaster; or Meindl et al, / Med, Chem" 1984, 27(9), 1111. Intermediate 61 446 4.08 442 Aldrich Intermediate 61 392 3.62 443 ςο m Aldrich Intermediate 61 418 3.83 444 U &quot; WO 01/38323 Intermediate 61 440 3.07 445 Aldrich Intermediate 61 408 3.31 446 H,N, / Acros Intermediate 61 471 3.13 87841-960303-中.doc 268 - 1283678 447 points 〇r- Peakdale Molecular Company Intermediate 61 435 3.13 448 CH, 〇= R=〇u &quot; Peakdale Molecular Company Intermediate 61 456 3.32 449 CH, u &quot; Peakdale Molecular Company Intermediate 61 436 3.56 450 M, / Aldrich Intermediate 61 471 2.79 451 Ί H3c_0 ^ Na J, Med, Chem., 1982, 25(12), 1442 Intermediate 61 465 3.11 452 ABCR Intermediate 61 464 3.47 453 Matrix Science; or Chem. Ber" 1969, 102, 2770 Intermediate 61 407 3.35 454 Aldrich Intermediate 61 411 3.18 455 &quot;X)u. Aldrich Intermediate 61 407 3.3 456 Aldrich Intermediate 61 423 3.09 457 ( CF3 C(0)OH salt) CT&quot; Aldrich Intermediate 61 379 2.92 458 FX^Tm F Aldrich Intermediate 61 414 3.68 459 Aldrich Intermediate 61 404 3.72 460 (for CF3 C(0)0H salt) in, Aldrich Middle Object 61 421 3.29 87841-960303-中.doc -269- 1283678 461 Aldrich Intermediate 61 396 3.58 462 H,c,0 CH, Aldrich Intermediate 61 438 3.53 463 (for CF3 C(0)0H salt) Inorganic Chemistry, 1997, 36(9), 1967 Intermediate 61 413 3.4 464 (for cf3 c(〇)〇h salt) CH, Human A Peakdale Molecular Company Intermediate 61 449 3.18 465 ABCR Intermediate 61 422 3.77 466 (5^ Aldrich Middle Object 61 404 3.72 467 Pfaltz-Bauer; or Meindl et al, J, Med·Che Mt 1984, 27(9), 1111. Intermediate 61 446 3.85 468 CH, Peakdale Molecular Company Intermediate 61 436 3.53 469 Aldrich Intermediate 61 404 3.66 470 Aldrich Intermediate 61 435 3.52 471 Esprit Intermediate 61 370 2.82 472 λΤ Apollo Intermediate 61 444 3.63 473 MicroChemist ry- RadaPharma π Intermediate 61 399 3.16 87841-960303-中.doc -270- 1283678 474 0C Fluka Intermediate 61 430 3.72 475 J. Am. Chem. Socty 1977, 99, 3075 Intermediate 61 421 3.04 477 H, C, n/CH3 J. Org. Chem., 2001, 66(6), 1999 Intermediate 61 421 2.89 478 FJX&quot; Aldrich Intermediate 61 396 3.59 479 Aldrich; or Meindl et al., / Med , Chem., 1984, 27(9), 1111. Intermediate 61 446 3.80 480 6c Aldrich Intermediate 61 414 3.57 481 Aldrich; or Meindl et al, / Med. Chem" 1984, 27(9), 1111. Intermediate 61 396 3.62 482 Aldrich Intermediate 61 446 3.82 483 1 Med. Chem., 2001, 44(26), 4628 Intermediate 61 438 3.95 484 WO 9417035 Intermediate 61 485 , 〇&quot;〇, Aldrich Intermediate 61 394 3.61 486 MicroChemist ry- RadaPharma Intermediate 61 395 2.78 487 Aldric h Intermediate 61 379 2.71

Example 488: 4-[({[4-(cyclohexylamino)-1-ethyl-1H-pyrazolo[3,4-b]pyridin-5-yl]carbonyl}amino)methyl]benzene Formic acid -271 - 87841-960303-中.doc 1283678

2M-sodium hydroxide solution (29 microliters, 0.058 millimoles) was added to a stirred solution of example 470 (6 mg, 0.014 mmol) in methanol (28 microliters) and water (2 microliters) . The resulting solution was stirred at 50 ° C under nitrogen. After 16 hours, the mixture was diluted with water (0.5 ml) and adjusted to pjj4 with acetic acid. The solids from the sinking chamber were collected by filtration and dried in vacuo to give a white solid (4.5 mg). LCMS showed MH+ = 422; Tret = 3.26 min. Example 489: 3_[({[Winter (cyclohexylamino))ethylethylpyrazolo[3 4-7]indolepyridinyl]carbonyl}amino)methyl]benzoic acid

2M-sodium hydroxide solution (83 μL, 〇·ΐ 66 mmol) was added to Example 468 (18 mg, 0.042 mmol) stirred in methanol (88 μL) and water (5 μL) In solution. The resulting solution was stirred at 50 ° C under nitrogen. After 16 hours, another quantity of 2M-sodium hydroxide solution (29 μL, 〇·〇 58 mmol) was added to the reaction mixture from 87841-960303-medium.doc-272-1283678. After 24 hours, the reaction mixture was diluted with water (5 mL) and adjusted to pH 4 with acetic acid. The mixture was extracted with ethyl acetate (2×0.5 mL), and then evaporated and evaporated. This solid was purified on a SPE cartridge (silica gel, 1 g) eluting with ethyl acetate: cyclohexane (1:1) followed by methanol. The fractions containing the desired product were combined and concentrated to give a white solid (4.6 mg). LCMS showed MH+ = 422; TRET = 3.22 min. Complex: 4_(cyclohexylamino)_N_(2,3_dihydro_111_茚_2_yl) small ethyl-1H-pyrazolo[3,4-7]pyridine-5-carboxamide salt

Example 469 (71 mg, 0.17 mmol) in EtOAc (2 mL) After standing at ambient temperature for 16 hours, the solid which formed was collected by filtration and dried under vacuum to afford s. LCMS shows -404, Tr e τ = 3.60 minutes. Free 491 : 4_(cyclohexylamino) with (2,3-dihydro-1H-茚_2-yl) small ethyl-iH-pyrazolo[3,4-7]pyridine-5-carboxamide Methanesulfonate 87841_96〇3〇3-中.doc -273 - 1283678

An example solution of 469 C 71 mg, 0.17 mmol, in anhydrous EtOAc (2 mL). After standing at ambient temperature for 16 hours, the solid which formed was collected by filtration and dried under vacuum to give </ RTI> </ RTI> as a rod crystal (23 mg). Lcms shows MH+= 404; TRET= 3.59 minutes. , example 492-649

General Procedure A mixture of Intermediate 33 (0.1 mmol), _ ((U Mill) &amp; DIpEA (〇 4 mmol) in DMF (0.4 mL) was shaken at room temperature for 1 Torr. A solution of the amine (0.1 mmol) in DMF (0.2 mL) was added and the mixture was stirred for a few minutes to give a solution. The solution was stored at room temperature for 16 hours, then concentrated in vacuo. The residue was dissolved in chloroform. (0.5 ml) and applied to the SPE cartridge (aminopropyl, 〇·5 g). The cartridge was continuously vented (1·5 mL), EtOAc (1.5 mL) and EtOAc: MeOH (9: 1.15 ml) Dissolve. Dissolve the fractions containing the desired product in vacuo and purify the residue by preparative HPLC by mass guidance. 87841-960303-中.doc -274- 1283678 Example No. NR4R5 Source of hnr4r5 MH+ ion LC-MC retention time 492 (for CF3 C(0)0H salt) OC&quot; Peakdale Molecular Company Intermediate 33 453 2.90 493 XT- Maybridge Chemical Company; or WO 01/30745 Intermediate 33 428 2.92 494 Trans World Chemical company; or DE 1953059 Intermediate 33 428 2.91 495 (V&q Uot; Fluorochem Intermediary 33 446 2.70 496 Peakdale Molecular Company Intermediate 33 438 2.83 497 qrm r Peakdale Molecular Company Intermediate 33 438 2.79 498 ςτ&quot; Fluorochem Intermediary 33 446 2.73 499 Aldrich Intermediate 33 426 2.50 500 Nippon Kagaku Zasshi 1952, 73; 393 Intermediate 33 438 2.62 87841-960303-中.doc 275 - 1283678 501 Apollo Scientific Company Intermediate 33 462 2.88 502 Apin Chemical Company Intermediate 33 437 2.19 503 Sigma Intermediate 33 410 2.60 504 Aldrich Middle 33 428 2.80 505 VII. tx^ Miteni SpA Intermediate 33 478 2.97 506 Aldrich Intermediate 33 424 2.58 507 J, Med·Chem.9 1997, 20(9), 1210 Intermediate 33 436 2.44 508 Also m Fluorochem Company Intermediate Substance 33 462 2.99 509 JP 11080156 Intermediate 33 473 2.2 510 /0 Aldrich Intermediate 33 454 2.41 512 Synchem OHG Intermediate 33 462 2.96 513 Apin Chemical Company Intermediate 33 454 2.59 514 J. Chem, Soc. Perkin Trans. 1 , 1977, 386 Intermediate 33 438 2.75 515 9C^ F SIGMA-RBI Intermediate 33 430 2.65 516 /0 WO 9303022 Intermediate 33 454 2.67 517 cc^ SIGMA-RBI Intermediate 33 408 2.73 87841-960303-中.doc 276- 1283678 518 Matrix Science; or Chem, Ber,, 1969, 102, 2770 Intermediate 33 408 3.2 519 H, C-0 wide J, Med, Chem.t 1982 25(12), 1442 Intermediate 33 466 3 521 〇々々〇Acros Intermediate 33 473 2.62 522 〇:; ch3 WO 01/38323 Intermediate 33 445 2.55 523 Aldrich Intermediate 33 394 3 524 CH, Aldrich Intermediate 33 423 2.51 525 Fxx^. Aldrich : Intermediate 33 412 3.06 526 Aldrich Intermediate 33 408 3.16 527 ςτ- Η, Ν-^=0 0 Yakugaku Zasshi; 1950 70,71 Intermediate 33 459 2.6 528 .xr- Aldrich; or Organic Letters, 2002, 4(12), 2055 Intermediate 33 394 3.08 530 Lancaster Intermediate 33 466 3.31 531 o;r H3c〆0 J, Am, Chem, Soc.} 1976, 78 (22), 6978 Intermediate 33 438 3 532 (for CF3 C(0)0H salt) ςτ^ Cl Inorganic Chemistry, 1997,36(9), 1967 Intermediate 33 415 2,82 87841-960303-中.doc - 277- 1283678 533 0^ Aldrich Intermediate 33 406 3.14 534 CC- Peakdalc Molecular Company Intermediate 33 451 2.71 535 Aldrich Intermediate 33 406 3.15 536 Aldrich Middle 33 406 3.15 537 J. Med. Chem., 1999, 42(14), 2504 Intermediate 33 473 2.58 538 ςο ch3 Chemical structure unit intermediate 33 422 2.92 540 9 Ν s Wn, Ch3 Aldrich Intermediate 33 451 2.13 541 9 V Aldrich Intermediate 33 436 .3.15 542 CP Aldrich Intermediate 33 408 • 2.85 544 j〇〇Janssen Potion Intermediate 33 449 2.67 545 jO1—Intermediate 69 Intermediate 33 444 2.34 546 (for HC(0)0H Salt = Formic acid addition salt) 〇, Arzneimittel Forschungt 1974, 24(4a), 584 Intermediate 33 430 1.95

87841-960303-中.doc -278-1283678 547 WO 97/25323 Intermediate 33 445 1.96 548 (for CF3C(0)0H salt) OjCT&quot; WO 03/32980 Intermediate 33 479 2.21 549 (for CF3 C(0) 0H salt) WO 03/32980 Intermediate 33 492 2.24 550 (for CF3 C(0)0H salt) WO 02/85860 Intermediate 33 424 2.33 551 Salor Intermediate 33 422 3.36 552 9 WO 95/00516 Intermediate 33 494 3.22 553 (for CF3C(0)0H salt) XuD^ WO 03/32980 Intermediate 33 492 2.21 554 1 ct^ Aldrich; or Mdndl et al, J, Med. Chem., 1984, 27(9), 1111. Intermediate 33 448 3.4 555 Aldrich Intermediate 33 416 3.06 556 FiVm Salor Intermediate 33 432 3.21 557 h, c,. ^ ο DE 2300018 Intermediate 33 458 3.12 558 4 Pcakdale Molecular Company Intermediate 33 436 3.41 87841-960303-中.doc • 279- 1283678 559 (for CF3 C(0)OH salt) oJ JP 10045736 Intermediate 33 463 2.28 560 WO 02/16318 EP 338793 Intermediate 33 487 2.74 561 H,. , H, 〆 Maybridge Chemical Company Intermediate 33 440 2.99 562 H, C CH, Lancaster Intermediate 33 440 3,00 563 Aldrich Intermediate 33 398 3.01 564 F Aldrich; or Meindl et al, J. Med. Chem.y 1984 , 27(9), 1111. Intermediate 33 416 3.11 565 Aldrich; or Organic Letters, 2002, 4(12), 2055 Intermediate 33 414 3,19 567 Aldrich Intermediate 33 372 3.01 568 7. Biol Chem,, 1997 , 272(3), 1493 Intermediate 33 472 2.69 569 Fluorochem Company Intermediate 33 466 3.29 570 utW=\^° Intermediate 71 Middle Question 33 463 2.66 571 Maybridge Sih Intermediate Intermediate 33 478 2.25

87841-960303-中.doc 280 - 1283678 572 WO 99/67204 Intermediate 33 463 2.24 573 4ϊΤ, 丨Eur. J, Med. Chem” 1987, 22(5), 417 Intermediate 33 450 2.90 574 Cl Lancaster Intermediate 33 446/ 448/ 450 3.35 575 Eur. J, Med. Chem.y 1987, 33(5), 363 Intermediate 33 436 3.48 576 Avocado Intermediate 33 416 3.06 577 WO 02/30930 Intermediate 33 458 2.80 578 ^0H Apin Intermediate 33 458 2.80 579 0—Aldrich Intermediate 33 458 2.80 580 Aldrich Intermediate 33 581 Cl Lancaster; or J, Med. Chem. 9 1984, 27(9), 1111. Intermediate 33 446/ 448/ 450 2.80 582 Aldrich Intermediate 33 440 2.96· 583 Aldrich Intermediate 33 410 2.98 584 ICN Biological Sauce Company; or Salor; Good Synthesis, 1982, 12, 1036 Intermediate 33 408 3.18

87841-960303-中.doc 281 - 1283678 585 Η- WO 03/32986 Intermediate 33 437 2.62 586 Aldrich Intermediate 33 424 3.05 587 Aldrich Intermediate 33 414/ 416 3.13 588 Buttpark Intermediate 33 396 2.14 589 Aldrich Intermediate 33 424 2.76 590 Lancaster Intermediate 33 396 2.95 591 Aldrich; or Synlett, 1999, 4, 409 Intermediate 33 386 3.10 592 &amp; Aldrich Intermediate 33 593 Apin Intermediate 33 438 2.82 594 Aldrich; or Meindl et al, J. Med, Chem .j 1984, 27(9), 1111. Intermediate 33 448/ 450/ 452 3.26 595 WO 02/85860 Intermediate 33 423 2.29 596 F Aldrich Intermediate 33 416 3.0 597 Aldrich Intermediate 33 423 2.56 598 Apin 33 396 2.54 599 WO 00/17163 Intermediate 33 411 2.72 600 Aldrich; or J. Med. Chem.t 2003, Intermediate 33 381 1,89

87841-960303-中.doc-282- 1283678 46(4), 461. 601 Aldrich; or Meindl et al, J, Med. Chem.y 1984, 27(9), 1111. Intermediate 33 448 2.96 602 Peakdale Molecules Intermediary 33 423 2.28 603 WO 94/17035 Intermediate 33 437 2.28 604 J. Pharm Sci.t 1987, 76(1), 18-20 Intermediate 33 437 2,34 605 Mbvj0^F Aldrich; or Meindl et al Human, J. Med. Chem., 1984, 27(9), 1111; A Organic Letters^ 2002, 4(12), 2055 Intermediate 33 398 2.71 606 &quot;Ί&gt;ηΛ〇Lis et al., / Med. Chem .y 1990, 33(10), 2883, see 囷Form III and Reference 24 Intermediate 33 473 2.40 607 Sigma Intermediate 33 459 2.31 608 Η,Ν^Ο Peakdale Molecular Company Intermediate 33 423 2.55 609 % Human Fluorochem Intermediate 33 · 446 2.82 610 - Ί〇ΓΎ DE 19937494 Intermediate 33 437 1.86 611 1 FluorochemL Scorpion 33 444 2.80 612 Τ γ WOOO/72834 Intermediate 33 415 2.12 613 F^F Aldrich Intermediate 33 448 2.96 87841-960303 - 中.doc 283 - 1283678 615 m J, Med, Chem, y 2001, 44(26), 4628 Intermediate 33 440 3.03 616 Intermediate 75 (for HC1 salt) Middle 33 451 2.62 617 Aldrich; or Organic Letters, 2002, 4(12), 2055 Intermediate 33 398 2.90 618 Alfa Intermediate 33 466 2.98 619 Energy &amp; Fuels, (1994), 8(4), 990-1001 Intermediate 33 408 2.86 620 Alfa Intermediate 33 466 2.94 621 Apollo Intermediate 33 434 2.82 622 Acros Intermediate 33 432 2.9 623 Acros Intermediate 33 476 2.95 624 Apollo; or Eur. J. Med, Chem.y 1998, 33(5) , 363 Intermediate 33 408 2.88 625 ^ir Maybridgc Intermediate 33 408 2.83 626 Lancaster Intermediate 33 448 3.02 627 Apin Intermediate 33 405 2.56 628 &quot;Π. Ubi-Chem W object 33 458 2.89 87841-960303-中. Doc 284- 1283678 629 F ABCR Intermediate 33 466 2.97 630 Lancaster Intermediate 33 505. 9 2.97 63 i Apollo Intermediate 33 436 3.11 632 WO 98/33767; or Meindl et al, J. Med. Chem.f 1984, 27 (9), 1111. Intermediate 33 405 2.55 633 Pfaltz-Bauer; or Meindl et al Med, Chem.t 1984, 27 (9), 1111 Intermediate 33 448 2.88 634 a Transworld Intermediate 33 428 3.22 635 B- Apin (as HC1 Salt use) Intermediate 33 536 3.47 636 Matrix Intermediate 33 408 3.18 637 &quot;XC Avocado Intermediate 33 466 3.25 638 Pfaltz-Bauer Intermediate 33 505. 9 2.92 639 Alfa Intermediate 33 458 3.10 640 OH WO 03/35621 (used as HC1 salt) Intermediate 33 410 2.49 641 WO 03/35621 (Used as HC1 salt) Intermediate 33 410 2.51 642 DE 2136624 (used as HC1 salt) Intermediate 33 424 2.55

87841-960303-中.doc -285 - 1283678 643 Q (used as HCl salt) Intermediate 33 478 2.96 644 Aldrich Intermediate 33 462 3.13 645 中间 Intermediate 33 436 3.18 646 Matrix Intermediate 33 408 2.84 647 F Apollo Intermediate 33 434 2.80 648 ABCR Intermediate 33 466 2.99 649 Lancaster Intermediate 33 428 2.87 Example 518 ·· N-[(3,4-dimethylphenyl)methyl]_1_ethyl-4-(tetrahydro-2H _piperan-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine_5-formamide; also known as: n_(3,4-dimethylbenzyl)-1_ Ethyl_4_(tetrahydro-2Η-piperidin-4-ylamino)_ih-pyrazolo[3,4_b]pyridine-5-carboxamide

An alternative method for the preparation of Example 518 is shown below: in a solution of Intermediate 33 (3.5 g ' 12.07 mmol) in DMF (500 mL), add -286- 87841-960303-中.doc 1283678 HATU (4.5 g, 12.07 mmol) and the mixture was stirred at room temperature for 30 min. Add 3,4-dimethylbenzylamine (1.63 g, 12.07 mmol, available from Mstrix Scientific, Clumbia, USA or by C/^m. price r., 1969, 102, 2770) ), followed by DIPEA (4.5 mL, 26.55 mmol), and the solution was stirred at room temperature for 16 hours. The solvent was removed under reduced pressure and the residue was crystallised eluted eluted eluted eluted The extracts were combined, dehydrated (Na2S04), and evaporated. The resulting viscous oil was recrystallized from EtOAc (EtOAc:EtOAc) LCMS showed MH+ = 408; Tret = 3.06 min. 5 η (D6 DMSO) 1 ·36 (3H,t),1 ·51 (2H,m), 2.00 (2H,m),2· 18 (3H,s), 2·19 (3H,s), 2.50 (2H,m), 3.61 (2H,m),3.83 (2H,m),4·17 (1H,m),4·36 (2H, q),4·38 (2H,d),7.02-7.09 (3H, m), 8.17 (1H, s), 8.62 (1H, s), 8.93 (1H, t), 9.96 (lH, d): 5 c (D6DMSO) 14.65, 18.91, 19.33, 32.81, 41.06, 41.86 , 48.57, 4.94, 101.69, 102.18, 124.44, 128.22, 129.24, 133.28, 134.31, 135.78, 136.91, 1 49.26, 149.59, 151.36, 168.81 Example 518A: N-[(3,4-dimethylphenyl)methyl ]-1_ethyl-4·(tetrahydro-2H·piperidin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide hydrochloride; also known as Is: N-(3,4-dimethyl-aryl)-1-ethyl-4-(tetrazine-2H-bran-4-ylamino)-111-3⁄41 ratio also [3,4- b] Pyridine-5-methanamine hydrochloride 8878 卜9603〇3_中.doc -287-1283678 ο)

A solution of Example 518 (1,3 g, 3.19 mmol) in anhydrous tetrahydrofuran (200 mL) eluted with hydrogen chloride in dioxane (4M, 8 mL) and mixture at ambient temperature Stir for 16 hours. The resulting white solid was collected by EtOAc (EtOAc:EtOAc) LCMS showed MH+ = 408; Tret = 3.21 min. (5H(D6DMSO) 1.39 (3H, t), 1.59 (2H, m), 2.01 (2H, m), 2.19 (3H, s), 2·20 (3H, s), 3·64 (2H, t) ,3·83 (2H,m),4·28 (1H ,m)5 4.40 (2H,d),4.50 (2H,q),7·04·7· 11 (3H,m)5 9.40 (1H, s (br)), 10.72 (1H, s (br))·. Example 650: 4·丨({丨1·ethyl_4_(tetrahydro-s-furyl-4-ylamino)_ιη·pyrazolo[ 3,4-b]pyridin-5-yl]carbonyl}amino)methyl]benzoic acid

2M-sodium hydroxide solution (98 μL, 0.196 mmol) was added to Example 593 (22 mg, 0.049 mmol) stirred in methanol (1 〇 4 μL) and water (6 μL) In solution. The resulting solution was stirred at 50 ° C under nitrogen. After 16 hours - 288 - 87841 - 960303 - medium .doc 1283678, the reaction mixture was diluted with water (0.5 ml) and adjusted to ΡΗ4 with a cool acid. The mixture was extracted with ethyl acetate (2x 0.5 mL). This solid was suspended in water (0.5 ml) and treated with a 2M- sodium hydroxide solution (15 liter). The solvent was evaporated in vacuo to give mp. LCMS showed MH+ = 425; Tret = 2.69 min. Replicate 651 : 3_[({[1-ethyl_4-(tetrahydro-2Η-scarred-4-ylamino)-[3,4-pyridin-5-yl]carbonyl}amine Methyl]benzoic acid

2M-sodium hydroxide solution (98 μL, 0.196 mmol) was added to Example 558 (22 mg, 0.049 mmol) in methanol (1 〇 4 μl) and water (6 μL). In solution. The resulting solution was stirred at 50 ° C under nitrogen. After 16 hours, the reaction mixture was diluted with water (0.5 mL) and adjusted to pH 4 with acetic acid. The solid which had been precipitated was collected by filtration and dried in vacuo to give a white solid (15 mg). LCMS showed MH+ = 425; Tret = 2.72 min. Example 652: 1_Ethyl_4_{[4-(imido)cyclohexyl]amino}·1Η-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester 87841-960303- Medium.doc -289- 1283678

A mixture of 205 (200 mg), hydroxyamine hydrochloride (50 mg) and EtOAc (EtOAc) (EtOAc) The solution was allowed to cool and concentrated in vacuo. The residue was partitioned between Et〇Ac and water. The organic phase was separated, dried with EtOAc EtOAc EtOAc EtOAc LCMS showed MH+ = 346; Tret = 2.84 min. Example 653: 1-ethyl-4_{[4_(hydroxyimino)cyclohexyl]amino-based N-{[4-(methoxy)phenyl]fluorenyl}_1H-pyrazolo[3, 4-b]pyridine_5_formamide

A mixture of 263 (217 mg), hydroxyamine hydrochloride (43 mg), EtOAc (EtOAc) The solution was allowed to cool and concentrated in vacuo. The residue was partitioned between Et〇Ac and water. The organic phase was separated, dried with EtOAc EtOAc EtOAc LCMS showed MH+ = 437; TRET = 2.82 min. 5 H(CDC13) 1.49 (3H, t), 1·80 (2H, m), 2.2-2.4 (4H, m), 2·54 (1H, m), 3.13 (1H, dt), 3.81 (3H, s),4·13 (1H,m), 4.46 (23⁄4 q),4·54 (2H,d), 6.28 (1H,t),6.90 + 7·28 (4H,AA,BB,), 7.98 ( 1H, s), 87841-960303-中.doc -290- 1283678 8·36 (1H, s), 9.84 (1H, d). Hydroxy protons are not visible. The following examples are made by similar procedures:

Example No. NR4R5 Source of hnr4r5 Starting material MH+ Ion LC-MC Retention time 654 Aldrich Example 619 450 2.35 Replica 655_ : 1-ethyl_4-({4·[(ethoxy)imino]cyclohexyl} Amino)-Ν-{[4·(methoxy)phenyl]methyl b 1Η-pyrido[3,4-b]pyridine-5-carboxamide

Stir a mixture of Example 263 (25 mg), ethoxylamine hydrochloride (r26 〇nh2, </ RTI> </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> 20 mg) and diisopropylethylamine (30 mg) in acetonitrile (3 mL) And heated under reflux for 3.25 hours. The solution was allowed to cool and concentrated in vacuo. The residue was applied to an SPE cartridge (5 grams). Dissolve the cartridge with Et0Ae. The fractions containing the desired product were concentrated in vacuo to give s. s. LCMS shows _+=465; Tret==3 28 minutes. The following examples are made by a similar procedure. · 87841-960303-φ.ά〇〇 -291- 1283678

Example No. R26 r26onh2 Source Starting material MH+ Ion LC-MC Retention time 656 Me Aldrich Example 263 451 2.52 657 tBu Aldrich Example 263 493 3.66 Actual: 1-ethyl-N_{[4_(methoxy)phenyl] A H-[(7-ketohexahydro-1H-nitrohayrostenylene)amino]-1H-pyrazolo[3,4-7]pyridine-5-carboxamide

OMe A suspension of cyanuric chloride (150 mg) in DMF (0.2 mL) was stirred for 3 min. The suspension was diluted to 7 ml with DMF and stirred. The resulting suspension was removed and added to Example 653 (52 mg). The resulting solution was stirred for 90 hours and then concentrated in vacuo. The residue was partitioned between EtOAc and water. The organic phase was separated and washed successively with saturated sodium bicarbonate, 10% w/v EtOAc and saturated brine, dried over Na? The residue was applied to an SPE cartridge (2 grams). The cartridge was continuously lyophilized with EtOAc: cyclohexane (1:1), EtOAc then EtOAc (EtOAc:EtOAc) The fractions containing the desired product of 87841-960303-Meso.doc-292-1283678 (dissolved in an ammonia-containing solution) were concentrated in vacuo to give Example 658 as a colorless oil (11 mg). LCMS showed MH+ = 437; Tret = 2.50 min. Example 659: 1-Ethyl Winter [(7-ketohexahydro-1H--azopentylene-4-yl)amino]-1H-pyrazolo[3,4-b]pyridine-5-carboxylate Ethyl acetate

Example 659 was prepared using the same procedure as used in Example 658 from Example 652. LCMS showed MH+ = 346; Tret = 2.56 min. : 4·{[cis-ice (butylamino)cyclohexyl]amine-based N-(2,3-dihydro-1H-indole:yl)-1-ethyl-1H-pyrazolo[3,4_b Pyridine_5_formamide

A solution of 258 (25 mg), butyraldehyde (5 mg) and glacial acetic acid (3 mg) in DCM (3 mL) was stirred for 1 min. Sodium triethoxy borohydride (21 mg) was added. The reaction mixture was stirred for U hours. Sodium bicarbonate (1·molar, molar concentration, 3 ml) was added dropwise and stirred. After stirring for 5 minutes, the liquid phase was separated. The organic phase was dried over Na 2 S 〇 4 and applied to a SpE cartridge (5 g). Dissolve the cartridge with di-methane, ethanol and ammonia (100:8: mixture). The fraction containing the desired product is concentrated in vacuo to obtain the example 87841-960303-medium doc-293-1283678 660, which is amorphous. A creamy yellow solid (19 mg). LCMS showed MH+ = 346; Tret = 2.56 min. Examples 661 to 664 nhr3o

General Procedure: Intermediate 17 (0.16 mmol) in acetonitrile (1 mL) in EtOAc (1 mL) EtOAc (EtOAc &lt;RTI ID=0.0&gt; Molly) processing. The mixture was heated at 50 ° C for 18 hours and then concentrated in vacuo. The residue was diluted with water (3 mL) andEtOAc. The combined organic extracts were evaporated and the residue purified by preparative HPLC eluting with EtOAc. This material was dissolved in chloroform-methanol (10/1, 5.5 mL) eluted elute Example No. NHR3 r3nh2 Source Starting material MH+ Ion LC-MC Retention time 214 H2N-^^NH J· Med. Chem·, 1994, 37 (17), 2360 Intermediate 17 393 2.16 661 Aldrich Intermediate 17 393 2.16 662 ^^,λ',νη2 Aldrich Intermediate 17 393 2.29 663 Aldrich Intermediate 17 393 2.30 87841-96〇3〇3·中.doc -294- 1283678 664 h2K Peakdale Molecular Company Intermediate 17 393 2.21 For Examples 214 and 661 For NHR3 in -663, NHR3 is shown as a cis or trans isomer. For Examples 662-664, NHR3 is a 3-amino- or 2-amino-cyclohexan-1-ylamino group in racemic form. Example 6651·Ethyl_4-{[(lSR,3RS)_3-p-cyclohexyl]amino}_1H^ is more complex [3 4 is acridine-5-carboxylic acid ethyl ester

[cis-(3-hydroxycyclohex-1-yl)amine, racemic] 3-aminocyclohexanol (0.677) in acetonitrile (10 mL) and ethanol (1 mL) at room temperature克, 5.9 millimolar, as described in JC/zem·PerhVz 7hz like i, 1994, 537), added to intermediate 1 (1.24 g, 4·9 mmol) and diisopropylethylamine (4.26 ml, 24.5 mmol) in acetonitrile (25 mL) in a stirred solution. The resulting mixture was stirred at 85 ° C for 17 hours. The mixture was concentrated in vacuo and the residue was crystallised eluted eluting eluting eluting The liquid phase was separated, and the organic phase was dried (Na2SO4) and evaporated to give an orange-brown oil. The oil was purified by EtOAc (EtOAc EtOAc) (EtOAc) LCMS showed MH+ = 333; Tret = 2.76 min. Examples 666-676 87841-960303-中.doc -295 - 1283678

OH

[cis-(3-3⁄4-ylcyclohex-1-yl)amino, racemic] General leap year: intermediate 76 (0.1 mmol), HATU (0.1 mmol) &amp; DIpEA (〇 A mixture of 4 mmoles in DMF (0.5 mL) was shaken at room temperature for 1 min. Then a solution of the amine HNR4R5 (0.12 mmol) in DMF (0.5 mL) was added and the mixture was stirred for a few minutes to give a solution. The solution was stored at room temperature for 16 hours and then concentrated in vacuo. The residue was purified by HPLC on a mass-guided HPLC. 87841-960303·中.doc -296-1283678 Example No. nr4r&quot; Source of HNR4 R5 Starting material MH Dec. LC-MC Retention time 666 Aldrich Intermediate 76 332 2.35 667 Aldrich Intermediate 76 398 2.96 668 Μ) Manchester Organics Intermediate 76 401 2.48 669 Aldrich Intermediate 76 412 2.88 670 Acros Intermediate 76 472 2.57 671 Aldrich Intermediate 76 454 2.67 672 1 M3 Aldrich Intermediate 76 395 2.15 673 \^N ND Zelinsky Learning Intermediate 76 398 2,35 674 Matrix Science; or Chem· Ber” 1969, 102, 2770 Intermediate 76 422 3.08 675 Aldrich Intermediate 76 424 2.81 676 ICN Biopharmaceutical Company; or Salor; Good Synthesis, 1982, 12, 1036 Intermediate 76 422 3.08 Example 26 〇 (alternative procedure) Ν-[(2,4·Dimethylphenyl)methyl]sodiumethyl-4-[(4-ketocyclohexyl)amino]_1H-pyrido[3,4- b]峨淀-5-甲甲胺

-297 87841-960303-中.doc 1283678 Alternative procedure for Preparation Example 260: Intermediate 58 (45 mg), 11\1!; (63 mg) and 〇正八八(39 mg) in acetonitrile (5 ml) The solution in the solution was stirred for 10 minutes. A solution of 2,4-dimethylbenzylamine (24 mg X available from Sallor; or ICN Biomedical; or ICP/1982, 12, 1036) in acetonitrile (1 mL) was added. The reaction mixture was stirred for 18 hours. The solution was concentrated and the residue was partitioned between ethyl acetate (25 ml) and EtOAc. The organic phase was separated, washed with water <RTI ID=0.0>(20 </RTI> <RTI ID=0.0></RTI> </RTI> <RTIgt; </RTI> <RTIgt; Dissolve the cartridge with ethyl acetate. The fractions containing the desired compound were combined and concentrated in vacuo to afford </RTI> </RTI> <RTIgt; </RTI> <RTIgt; 511 (0〇(:13)·· 1.49(3H,t), 2.11(2H,m), 2.33 (3H,s), 2.35 (3H,s),2·40 (2H,m),2·52 (2H,m),2·61 (2H,m),4·36 (1H,m), 4·47 (2H,q),4·55 (2H,d),6·14 (1H,t) , 7.01 + 7.18 (2H, ΑΑΉΒ,), 7.04 (1H, s), 8.01 (1H, s), 8.36 (1H, s), 9.96 (1H, d). The following examples are similar examples after 677-679 The method of 260 (the above alternative procedure) is made, for example, using the same or similar molar reagents with the same or similar volume of solvent:

87841-96〇3〇3-中.doc -298-1283678 Example No. NR4R? HNR4 Source of R5 Starting material MH+ Ion LC-MC Retention time 677 -m5rci Lancaster Intermediate 58 460 3.28 678 NH Maybridge Chemical Company; or W0 01/30745 Intermediate 58 440 3.25 679 butyl nm Wc^rld Chemical Company or DE 19^059 Intermediate 58 440 3.24 Example 680-686 Example 680-686 is made by a procedure similar to that shown above for Example 653 For example, using the same or similar molar reagents with the same or similar volumes of solvent:

Example No. NR^ HNR4 R5 Source Starting Material MH+ Ion LC-MC Retention Time 680 Salor; or ICN Bio-salt Rough Company; or Synthesis, 1982, 12, 1036 Example 260 435 3.10 87841-960303·中.doc 299- 1283678 681 CHMSRV-AS; or Matrix Science; or Cherru Ber^ 1969, 102, 2770 Example 261 435 3.08 682 Lancaster Example 677 475 3.20 683 V:, Maybridge Chemical Company; or W001/30745 Example 678 455 3.17 684 %. Trans World Chemicals 彡 or DE 1953059 Example 679 455 3.17 685 Fluorochcxn; or WO 98/45268 Example 266 473 3.00 686 Aldrich; or Mcindl et al, / MccL Chcnu% 1984, 27(9), 1111; or 〇, · Lett,, 2002, 4(12), 2055 Example 267 475 3.13 t Example 681: N-[(3,4-Dimethylphenyl)methyl]_1-ethyl-4-{[4-(hydroxy Preparation of hydrazine by the substitution of amino)cyclohexyl]aminopyr 1H-pyrazolo[3,4-b]pyridine-5-carboxamide.

A mixture of 261 (35 mg), EtOAc (EtOAc) (EtOAc) The solution was allowed to cool and concentrated in vacuo. The residue was partitioned between EtOAc and water. The organic phase was separated, dried over Na2SO4, and concentrated in vacuo. The residue was applied to an SPE cartridge (10 grams). The cartridge was EtOAc (EtOAc): EtOAc (EtOAc) The fractions containing the desired compound were combined and concentrated in vacuo to afford crystals (yield: 18 mg). LCMS showed MH+ = 435; T rt = 3.08 min. δ η (CDC13) 1.49 (3H, t), 1.79 (2Η, m), 2.24 (6Η, s), 2.19-2.38 (4Η, m), 2.56 (2H, dt), 4.13 (1H, m) , 4.46 (2H, q), 4.53 (2H, d), 6.36 (1H, t), 7.09 (2H, t) 5 7.1 2 (1H, s), 7.98 (1H, s), 8.38 ( 1H, s), 9.79 (1H, d)· Hydroxy protons are not visible. 87841-960303-中.doc 301 -

Claims (1)

12 气养^哲举j Pick up, Fan Yuan: 1. A compound of formula (I) or its salt, /R3 HN 0 N^n^^r2 (I) R1 r1 is Ci-3 alkyl, Ci_2 fluoroalkyl or -CH2CH2OH; R2 is a hydrogen atom (hydrazine), a fluorenyl group or a q-fluoroalkyl group; R3 is a substituted C3-8 a heterocyclic group substituted by a cycloalkyl group or a subtype (aa), swollen) or (cc); (aa) r^)n2 (cc) or ((10) or wherein η1 and η2 are independently 1 or 2; and wherein γ is ο, s, S〇2 or NR10; wherein R10 is a hydrogen atom (Η), a methyl group, an ethyl group, a c(0) NH2, C(O)methyl or c(o)-cf3; and wherein when R3 is a substituted C:3·8 cycloalkyl group, then R3 is a cyclohexyl group substituted by a substituent, and the substituent is Keto group (=〇), 〇H, NHr2 1, wherein R2 i is a nitrogen atom (8) or Ci -5 straight bond, -CH2 OH, -C(0)0R2 3, wherein r2 3 is Η or methyl, -C(0)NHR24, wherein R24 is hydrazine, hydroxyimino (=N_〇h) or (Ch alkoxy)imido (=N-OR26, wherein R26 is aCh alkyl); and any The 0H or NHR21 substituent is not substituted at the R3 ring carbon attached (bonded) to the formula 1___ group; 87841-960303.doc 1283678 and wherein the R3 heterocyclic group of the subtype (aa), (bb) or (cc) The group is optionally substituted by one or two keto (==〇) substituents; and X is NR4R5 or 〇R5a, wherein: R4 is a hydrogen atom (H); and R5 is (^_8 alkyl; Ch halothane a C3_8 cyclodecyl group substituted by a ^2 alkyl group; or an alkyl group, optionally in the -(CH2)n4- moiety or in a C:3_8 cycloalkyl group a moiety substituted by (^_2 alkyl, wherein n4 is 1, 2 or 3; or R5 is C2_6 alkyl, substituted by one or two independent substituents Rn; wherein each substituent R11, and any other present The Ri 1 substituent is irrelevant and is: hydroxy (0H); (ν6 alkoxy; phenyloxy; benzyloxy; ;-NR1 5 ((COR1 6 ; -NRi 5 _c(〇)_〇ri 6 ; -NRi 5 ·0(〇)-Ν]ΗμΚι 5 ; or -NR1 5 -SC^R16 ; and any of the Ri 1 substituents, which are 〇H, alkoxy or -NR12Ri3, will not be in any oxime or ^Substituted alkyl (which is bonded to the nitrogen of NR4R5) is substituted at any carbon atom; or R5 is _(CH2)n&quot;-C(0)RH;_(CH2)ni2_c(0)0Rl6;CH2)n12-C(0)0H;-CHR19-C(0)0R^;-CHR19-C(0)0H;-(CH2)n^-S02.NR^Ri3; .(CH2)ni2.s〇 2Ri6 ; .(Ch2), 12.CN ; where n11 is 1, 2, 3 or 4, and n12 is 1, 2, 3 or 4; 2, 3 or 4, and Het is or R5 is -(CH2)n 1 3 -Het, wherein ηι 3 is an anthracene, 4-, 5-, 6- or 7-membered saturated or partially saturated heterocyclic ring containing one or two heteroatoms independently selected from OS and &gt;1; Any ring hetero atom, when When 13 is working, it will not bind to the _(CH2)nl3_ moiety, and when nl3 is 〇, it will not bind to the nitrogen of NR4R5; it exists and is not unsaturated (meaning it is not 87841- 960303.doc -2 - I283678 Any ring nitrogen involved in a double bond) is present as NR17, wherein R17 is as defined herein; and one or two of the carbon ring atoms are independently substituted by C! _2 alkyl as appropriate; R5 is phenyl, optionally substituted by one, two or three of the following groups: halogen atom; alkyl group; (^2 fluoroalkyl; Ch alkoxy; fluoroalkoxy; C3_6 cycloalkyloxy ;-C(0)R16a ; _C(0)OR30 ; ·8(0)2-Ι116&amp;;R16 aS(0)2 -NR15 a-; R7R8N-S(0)2 ; q -2 alkyl-( XCO-R1 5 aN-S(0)2; q.4 alkyl-s(0)-, Ph-S(O)-, R7R8N-CO-; -NR15-(:(0)1116 ; R7R8N '〇 This (^1-4 alkoxymethyl, (^_4 健乳基乙; (111-2 alkyl-8(0)2-(1!112-; R7 R8 NS(0)2 -CH2 - ; C 2 2 alkyl-S(0) 2 -NR15 a -CH2 - ; -CH2 ·0Η ; ch2ch2_oh; -ch2_nr7r8 ; -ch2-ch2-nr7r8 ; -ch2-c(o)or3〇;-CH2-C (0)-NR7R8; -CH2-NR15a-C(0)-CBu 3 alkyl; -(CHOnU-Het1 'where n14 is 0 Or 1; cyano (CN) or phenyl, wherein the phenyl group is optionally one or two fluoro, chloro, (2, alkyl, q, fluoroalkyl, Ck alkoxy or Q fluoroalkoxy Substituting; or wherein two adjacent substituents on the substituted phenyl group in R5 are taken together as -0-(CMe2)-a or -〇-(CH2)n14a-0-, wherein 1114& is 1 or 2 Wherein R7 and R8 are independently a hydrogen atom (H); q-4 alkyl or C3_6 cycloalkyl; or R7 and R8 are -(CH2)n6- or -C(0)-(CH2)n' Or -C(〇HCH2)n7-C(0&gt; or _(CH2)n 8 -X7 -(CH2 )n 9 _ or -C(0)-X7-(CH2)n10-, wherein: n6 is 3, 4, 5 or 6, n7 is 2, 3, 4 or 5, η8 and η9 and ηι〇 are independently 2 or 3, and X7 is 0 or NR14, wherein rH is Η, C卜2 burning base or C ( 0) Me ; or R 5 has the subtype (X), (y), (yl) or (z): 87841-960303.doc 1283678 -(CH2)n (x) Yang 2) (2) G Wherein in subtype (x), n = 0, ;! or 2; in sub-forms (7) and (5), (iv) or 2, and in sub-formula (8), r ==〇, 1 or 2; (x) and (y) and (y1), none or one or two of a, B, DE and F are independently nitrogen or nitrogen_oxide (Ν+-0·), provided that A, B, No more than one of D, E and F is nitrogen-oxide; and the remaining a, b, d, E and F are independently CH or Cr6; provided that when η is 〇 in sub-form (X), Then one or two of A, b, D, E and F are independently nitrogen or nitrogen-oxide (9) + _ 〇 -), and no more than one of a, b, D, E and F is a nitrogen-oxide; Wherein each R6, irrespective of any other R6 present, is: from an atom; a decyl group, a Cw fluoroalkyl group; a Q-4 alkoxy group; a fluoroalkoxy group; a fluorene 3-6 cycloalkyloxy group; C(0)R16a; -C(0)0R3°; .S(0)2.R^a ; R16a-S(0)2-NRl5a_; R7R8N_s(〇)2_; Ci2 alkyl_c(〇&gt;Rl5aN_s(〇)2_;q_4alkyl-s(0)-,R7R8N-CO-;-NR15-C(0)R16;r7r8n;OH; Ci-4 alkoxymethyl; cw alkoxyethyl; (: 2 alkyl-s(o)2-ch2_; R7 R8 NS(0)2 -CH2 - ; CBu 2 alkyl-S(0)2 -NR15 a -CH2 - ; CH2-OH; •ch2ch2-oh; -ch2-nr7r8; _CH2-CH2-NR7R8; -CH2-C(0)OR3〇, where n14 is 0 or 1; cyano (CN) or phenyl, wherein phenyl is The condition is substituted by one or two fluoro, chloro, q-2 alkyl, Q fluoroalkyl, Ci-2 alkoxy or 87841-960303.doc -4 - 1283678 q fluoroalkoxy; or two of them The adjacent R6 is taken as -〇_(CMe2)_〇_ or _〇-(CH2)n14a-〇-, where n14a is 1 or 2; wherein R7 and R8 are as defined herein; And (yi) are independently substituted by a ketone group (=〇) at the ring carbon of the adjacent 6-membered aromatic ring; wherein in the subtype (z), G is 0 or S or NR9, wherein R9 is Hydrogen atom (H), G-4 alkyl group or Ci-4 gas group; no or one, two or three j, l, Μ and Q are nitrogen; and the remaining J, L, Μ and Q are independently ch Or CR6, wherein R6, independently of any other R6 present, is as defined herein; and 1^ is &lt;^-8 alkyl or C!-8 fluoroalkyl; and wherein: R and R3 are each H ; c 5 5 alkyl; or phenyl, optionally taken by one or two tooth atoms ' Ci-2 alkyl, Q fluoroalkyl, cl-2 alkoxy or heart fluoroalkoxy ; or R12 and R13 are _(CH2)n6_ or _c(〇)_(CH2)n7_ or -C(0)-(CH2)n 7 -C(0)- or -(CH2 )n 8 - X12 -(CH2)n 9 - or -C(0)-X12-(CH2)n10-, where: n6 is 3, 4, 5 or 6, and n7 is 2' 3, 4 or 5 ' n8 and n9 and ni The oxime is independently 2 or 3, and χι 2 is 〇 or grabs 14 a, where R is a group or C(0)Me; R15 is a hydrogen atom (Η); CV4 alkyl; or phenyl, as the case may be Or two of the following groups are substituted: a halogen atom, a Ci 2 alkyl group, a fluorenyl 1 fluoroalkyl group, a Ci 2 alkoxy group or a Q fluoroalkyl alkoxy group; R 15a, which is independent of other R 15a, is a hydrogen atom (H) Or Ci4 alkyl; 87841-960303.doc 1283678 R16 and 1116&amp; are independently: Ci.6 alkyl; C3·6 cycloalkyl, optionally substituted by a keto group (=〇), alkyl substituent; C3_6 Cycloalkyl-CH2-; pyridyl, optionally substituted on the ring carbon atom by one of the following groups: halogen atom, q_2 alkyl group, Cl fluoroalkyl group, alkoxy group or (^fluoroalkoxy group; Ar5c Phenyl group, optionally substituted by one or two of the following groups: a halogen atom, a Ci alkyl group, a 4-fluoroalkyl group, a (^-2 alkoxy group or a heart-fluorenyl alkoxy group; a group, optionally substituted with one or two of the following base diagrams at the aromatic carbon atom: a halogen atom, a C 2 alkyl group, a q fluoroalkyl group, a Ck alkoxy group or a (fluoroalkyl alkoxy group; or 4- a 5-, 6- or 7-membered saturated heterocyclic ring which is attached at the ring-carbon and which contains one or two ring heteroatoms independently selected from 0, S and N; wherein any ring nitrogen is present NR27 is present, wherein 圮7 is η, c^2 alkyl or □(〇)Μ6; and wherein the ring is optionally substituted at the carbon by a q·2 alkyl or keto (=〇) substituent, Provided that any keto (= oxime) substituent is substituted at the ring-carbon atom bonded to the ring-nitrogen; wherein Ar5. a 5-membered aromatic heterocyclic ring containing a ruthenium, s or NR15a in a 5-membered ring, wherein the 5-membered ring may additionally contain one or two n atoms, and wherein the heterocyclic ring is optionally in the ring carbon The atom is substituted by one of the following groups: a functional atom, a Ci-2* group, a Ci fluoroalkyl group, a -CH2OH, a -CH2-OCi.2 alkyl group, and a hydrazine H (87841-960303.doc 1283678 including its ketone) Substituent) or _CH2-NR28R29 substituted, wherein R28 and R29 are independently hydrazine or methyl; and R1 7 is a hydrogen atom (H); Ch alkyl; C bis 2 fluoroalkyl; - (012) /-(:(0)1116 where P6 is 0, 1, 2 or 3; -(CH2)p6-C(0)NR12R13; -(CH2)P6-C(0)0R16; -(CH2)p 6 -C(0)0H; -S02 R16; -C(0)-CH2-NR12 R13; -C(0)-CH2-NR15 a -C(0)_U complete group; alkyl group; or phenyl or benzyl group Wherein the phenyl or fluorenyl group is optionally substituted at the aromatic carbon atom with one or two of the following groups: a halogen atom, a Ci 2 alkyl group, a Q fluoroalkyl group, a Ci-2 alkoxy group or a heart fluoride alkoxy group. 1119 is Ci-4 alkyl; -(CH2)n20-〇R20, wherein n2〇 is 1, 2, 3 or 4, and R20 is a hydrogen atom (H) or (: 4 alkyl; -CH ( Me)-0H ; -CH2_SH or -CH2 -CH -S-Me; and R3〇, independent of other r3〇, is a halogen atom (H), Ci_4 alkyl or alkyl; and Het1, independent of other Het1, is 4-,5_,6- Or a 7-membered saturated heterocyclic ring, attached at the ring-carbon, and containing one or two ring heteroatoms independently selected from the group consisting of hydrazine, S and N; wherein any ring-nitrogen present therein is present as NR31, wherein R31 is η, Q · 2 alkyl or -C(0)Me ; and wherein the ring is optionally substituted at the carbon by a Q-2 pit or a keto (=0) substituent, provided that any keto group (=〇) The substituent is substituted at the carbon-bonded to the soil of the soil nitrogen; the condition is: when R3 is a heterocyclic group of the formula (aa) and Y is NR10, then R1 Q is not C(0)NH2, C(0)methyl or C(0)-CF3; the conditions are: when R3 is a heterocyclic group of the formula (bb), η1 is 1, and γ is nrI 〇, Then 87841-960303.doc -7- 1283678: whether (a) R10 is not methyl or ethyl; or (b) R10 is methyl, and the compound is: 4-[(1-methylhexahydropyridine ice Amino]aminoethyl-1H-pyrazolo[3,4-b] is more than a bit of -5-", 2-ethyl-N-(2-ethylbutyl)-4- [(l-A Chloride p is more than -4-yl)amino]_ih-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-N-(4-fluorophenyl)·4- [(1-Methylhexahydropyridine-4-yl)amino]-1H-pyrazolo[3,4-b]pyridin-5-carboxamide, or N-mercapto-1-ethyl ice [ (1-methylhexahydropyridin-4-yl)amino]-1H-exocarbazo[3,4-7]pyridin-5-carbamamine; the condition is: when R3 is a subtype (cc) In the case of a heterocyclic group, NHR3 is a subtype (L), (m), (ml) or (m2) wherein the NHR3 group is bonded to the 4-position of the pyrazolopyridine 4-position Bottom line: And the condition is: in the case where R3 is a substituted C3_8 cycloalkyl group, then any 0H '·&lt;:Η2ΟΗ, -C(9)OR23, -C(0)NHR24 or -C(0)R25 substituent is located in the r3 ring. The 3-, 4- or 5-position of the hexyl ring (wherein the position of the r3 cycloalkyl ring is regarded as the point of attachment to -NH- in the formula (I)). 2. A compound of the formula (IA) or a salt thereof, Wherein: X is NR4R5 or 〇R5a, wherein: 87841-960303.doc 1283678 R4 is a gas, and 5 is &lt;^-8 alkyl, Cl-S fluoroalkyl or heart^cycloalkyl, phenyl, The situation is replaced by one or two of the following groups: a halogen atom, a c1-2 alkyl group, a trifluoromethyl group, a Cl_2 alkoxy group or a trifluoromethoxy group; or R5 has an Asian form (phantom, (magic or (z) : Wherein in the subtypes (8) and (z), n = 1 or 2; and in the subtype (y), my or 2; wherein in the subtypes (8) and (y), there is no or one or two A, B , D, E and F are nitrogen; and the remaining A, B, D, E and F are CH or CR6, wherein R6 is a halogen atom, Q-4 alkyl, Cm fluoroalkyl, Q-2 alkoxy, q _2 fluoroalkyl alkoxy, q · 2 alkylsulfonyl ((: 2 alkyl-S02-), (: 2 alkyl-SCVNH-, R7R8N-S02_, R7R8N-CO_, R7R8N, OH, Cw Alkoxymethyl or c 2 alkyl _S02-CH2- wherein R 7 and R 8 are independently hydrogen or c 2 alkyl; wherein in subformula (z), G is 0 or 8 or &gt; 19, wherein 妒 is a heart ^ alkyl or 4 4 fluoroalkyl; no or one or two of j, L, M and Q are nitrogen; and the remaining J, L, Μ and Q are CH or CR6, wherein R6 As defined herein; R is Ci-8 alkyl or 〇ι-8 gas; R3 is substituted c3_8 cycloalkyl or a heterocyclic group wherein Y is 0, 8, 802 or 1^10; wherein 111〇 is hydrogen, methyl, ethyl, C(0)methyl or c(o)-cf3; and wherein in R3 Wherein a C3-8 cycloalkyl group is substituted by an OH substituent to a cyclohexane 87841-960303.doc 1283678 group; and wherein any OH substituent is not attached to the ring carbon of the formula (ία)-NH- group Substituted; and RLCu alkyl or (^2 fluoroalkyl; The condition is: when R3 is a heterocyclic group of , , and Y is NR10, then R1() is not C(O)methyl or C(0)-CF3; the conditions are: a heterocyclic group, and when Y is NR10, then: (a) R10 is hydrogen, C(O)methyl or C(0)-CF3; or (b) R10 is methyl, and the compound is : 4-[(1-Methylhexahydropyridin-4-yl)amino]-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester, 1-B --N-(2-ethylbutyl)-4-[(1-methylhexahydropyridin-4-yl)amino]_1H-pyrazolo[3,4-b]pyridine-5-formamidine Amine, 1-ethyl-N-(4-fluorophenyl)_4-[(1·methylhexahydropyridin-4-yl)amino]-1H-pyrazolo[3+b]pyridine-5- Formamide or N-benzyl-1-ethyl-4-[(l-methylhexahydropyridin-4-yl)amino]-1Η-pyrazolo[3,4_b]pyridine-5-formamidine An amine; and the condition is: in the case where R3 is a substituted C3_8 cycloalkyl group, then the substituent is a substituent at the 3-, 4- or 5-position of the R3 cycloalkyl ring (wherein The 1-position of this R3 cycloalkyl ring is considered to be the point of attachment to -NH- in formula (IA). 3. A compound of the formula (IB) or a salt thereof, 87841-960303.doc -10- 1283678, R〇 Wherein: alkyl, Cl-2 fluoroalkyl or -CH2CH2〇H; R2 is a hydrogen atom (η), a fluorenyl group or a q-fluoroalkyl group; R is a substituted C3 -8 cycloalkyl group or a subtype (aa) a heterocyclic group substituted as appropriate by (bb) or (cc); Wherein η1 and n2 are independently 1 or 2; and wherein γ is 〇, s, S02 or NR10: wherein R10 is a hydrogen atom (H), methyl, ethyl, c(0)NH2, CX〇)methyl or c(o)-cf3; and wherein when R3 is a substituted C3-8 cycloalkyl group, R3 is a cyclohexyl group substituted by a keto group (=〇) or a 0H substituent; and wherein any 〇H substituent is not Substituting at the R3 ring carbon attached (bonded) to the formula (ΙΒ)-ΝΗ-group; and wherein the R3 heterocyclic group of the subtype (aa), (bb) or (cc) is optionally taken Substituted by two keto (=0) substituents; and X is NR4R5 or 0R5a, wherein: R4 is a hydrogen atom (H); and R5 is 4-8 alkyl; 〇ν8 fluoroalkyl; optionally by Cl-2 Alkyl substituted c3_8 cycloalkyl; or -(CH2)n4-C3-8 cycloalkyl, optionally in the group -(CH2)n4_part 87841-960303.doc -11 - 1283678 or in C3-8 a cycloalkyl moiety substituted by C^2 alkyl, wherein η4 is 1, 2 or 3; or R5 is C2_6 alkyl, substituted by one or two independent substituents R11; wherein each substituent R11, Any other R11 substituent present is: hydroxy (〇H); Ch alkoxy; phenyloxy;氧基; NR15-C(0)R16; NR15-Q〇)-0-R16; -NRB.qpyNH-Ris; or -NR15-S02R16; and any of the Rii substituents, which are 0H, oxygenated a group or -NR12R13, which is not substituted at any carbon atom of any R4 or R5 substituted alkyl group which is bonded to the nitrogen of NR4R5; or R5 is -(CH2)/4(0)1116; -(CH2 )^2-0(0)0^6 ; -CHR19-C(0)0R16 ; -(CH2)n12-S02-NR12R13 ; -(CH2)n12-S02RU ;4_(CH2)n12-CN; 2, 3 or 4, and nl2 is i2, 3 or 4; or R5 is -(CH2)n 13 -Het, where n13 is 〇, 1, 2, 3 or 4, and Het is 4-, 5-, 6 Or a 7-membered saturated or partially saturated heterocyclic ring containing one or two ring heteroatoms independently selected from 0, S and N; any ring heteroatoms present therein, when 〆3 is 1, do not bind to -(CH2)ni3_partial group, and when nn is 〇, it does not bind to the nitrogen of NR4R5; any ring nitrogen which is present and not unsaturated (that is, it does not participate in the double bond) is present, Wherein RW is as defined herein, and wherein one or two carbon ring atoms are independently substituted by A _2 alkyl as appropriate; or R 5 is phenyl, optionally _ or two Substituted by the following groups: _ atom, · Ch alkyl; Cl. 2 fluoroalkyl; Ch alkoxy; Ci2 fluoro alkoxy, · c &quot; burnt thiol (Cl_ into the base); , _; r7r8n_S (V 87841-960303.doc -12- 1283678; R7R8N-CO-; -NRU-CXO)!^; R7R8N; 0H; c 4 alkoxycarbonyl, 4-epoxyethyl, Q_2alkyl-S02-CH2-; cyano (CN); or phenyl, optionally with one or two fluoro, chloro, Cl 2 alkyl, (fluoroalkyl, Cl-2 alkoxy or heart) Fluoroalkyl alkoxy substituted; wherein R7 and R8 are independently a hydrogen atom (H); Cl-4 alkyl or C3 6 cycloalkyl; or R7 and R8 are _(οη2)Λ or -C(0&gt; (CH2)n7- or -C(0&gt;(CH2)n7-C(0&gt; or -(CH2)n 8 -χ7 -(CH2)n 9 - or -C(O)-X7-(CH2)n10_, Wherein: n6 is 3, 4, 5 or 6, n7 is 2, 3, 4 or 5, n8 and n9 and η1 are independently 2 or 3, and X7 is 〇 or NRi 4, wherein R14 is Η or (V2 Alkyl; or R5 has the subtype (X), (y) or (z): Wherein in the subtype (X), n=l or 2; in the subtype (y), ^=1 or 2; and in the subformula (z), r = 〇, 1 or 2; wherein in the subtype (x) and (y), none or one or two of A, B, D, E and F are nitrogen; and the remaining A, B, D, E and F are independently CH or CR6; Atom; cw alkyl; (: 4 fluoroalkyl; Ci-4 alkoxy; &amp; fluoroalkyl alkoxy; c 2 alkyl sulfonyl (Cl 2 alkyl 〇 2 〇; Ci 2 alkyl - S〇2-NH- , R7R8N-S02. ; R7R8N-CO- ; -NR15-C^R16 ; R7R8n , OH, Cw alkoxymethyl; q_4 alkoxyethyl; A. Alkyl_s〇2_CH2_ • cyano (CN); or phenyl, optionally substituted by one or two fluoro, chloro, A, hydroxy, hydroxy, chloro, or fluoroalkoxy; 87841-960303.doc -13 - 1283678 R7 and R8 are as defined herein; wherein in the subtype (z), G is 0 or S or NR9, wherein R9 is a hydrogen atom (Η) Cl-4 atomic group or C卜4说悦基; no or one, two or three J, L, Μ and Q are nitrogen; and the remaining j, L, M and Q are independently CH or CR6, wherein R6 is as defined herein; Or (:; 1-8 fluoroalkyl; and : R12 and R13 are independently H; q-5 alkyl; or phenyl, optionally substituted by one or two of the following groups: a halogen atom, a Cl-2 alkyl group, a fluoroalkyl group, an alkoxy group or a q Fluoroalkoxy; or R12 together with R13 is _(CH2)n6_ or -C(〇)-(CH2)n7_ or -C(〇HCH2)n7-C(0&gt; or _(CH2)n 8 -X12 -(CH2)n 9 - or -C(0)-X12-(CH2)n10-, wherein: n6 is 3, 4, 5 or 6, n7 is 2, 3, 4 or 5, η8 and n9 &amp; niG Independently 2 or 3, and χΐ2 is osnrH, wherein R14 is oxime or (V2 alkyl; R15 is hydrogen atom to (H); q-4 alkyl; or phenyl, optionally with one or two of the following groups Substituted: a functional atom, a Ci-2 alkyl group, a (fluoroalkyl group, an alkoxy group or a q-fluoroalkoxy group; R is a Ci-4 alkyl group; a C3-6 ring 婉* group; Or a phenyl group' is optionally substituted with one or two of the following groups: a south atom, a Ci-2 alkyl group, a (fluoroalkyl group, a Ci-2 alkoxy group or a fluoroalkyl alkoxy group; (H); Ch alkyl; Cu fluoroalkyl; -(CH2)p6-C(0)R16 wherein P6 is 0, 1, 2 or 3; -(CH2)p6-C(0)NR12R13; CH2)p6-C(0)0R16; -so2r16; or phenyl or benzyl, of which phenyl 8784 1-960303.doc -14- 1283678 or an aromatic carbon atom of a benzyl group is optionally one or two from an atom, a c alkyl group, a Ci fluoroalkyl group, a Ci-2 alkoxy group or a (fluoroalkyl alkoxy group). Substituting; and R19 is a Ch alkyl group; -(CH2)n20-OR20, wherein #〇 is i, 2, 3 or 4, and R 2 G is a hydrogen atom (H) or a C 4 alkyl group; -CH(Me)- OH; -CH2_SH or CH]-CH--S-Me; provided that when R3 is a heterocyclic group of the formula (aa) and γ is nrIG, then R10 is not C(0)NH2, C (0) methyl or C(0)-CF3; the conditions are: when R3 is a heterocyclic group of the formula (bb), η1 is 1, and Y is NR10: then: (a) R1G Not methyl or ethyl; or (b) R1G is methyl, and the compound is: 4-[(1-methylhexahydropyridin-4-yl)amino]ethylidene-1H-pyrazolo[ Ethyl 3,4-b]pyridine-5-carboxylate, 1-ethyl-N-(2-ethylbutyl)-4-[(1-methylhexahydropyridyl)amino]-1Η -pyrazolo[3,4-b]pyridine-5-decylamine, 1-ethyl-indole-(4-fluorophenyl)-4-[(1-methylhexahydropyridin-4-yl) Amino]-lH-p than spit[3,4-b]p than yt-5-cartoamine or oxime-yl-1_ethyl_4-[(1-methylhexahydropyridine-4 -yl)amino]-1H- Zizo[3,4-b]pyridine-5-formamide; provided that when R3 is a heterocyclic group of the formula (aa), NHR3 is a subtype (L), (m) or ( Ml), wherein the NHR3 group is paired with the formula (IB): the ratio of the Jun-p and the 4-position-NH-linkage is bottomed: X^NH NH Ο (m) (m1); and the condition is: in the case where R3 is a substituted C3_8 cycloalkyl group, then the 87041-960303.doc -15-1283678 substituent is located at R3 naphthenic A substituent at the 3-, 4- or 5-position of the base ring (wherein the 1-position of the R3 cycloalkyl ring is regarded as the point of attachment to -NH- in the formula (IB)). 4. A compound or salt according to claim 1 or 3 wherein R2 is a hydrogen atom (8). The compound or salt according to any one of claims 1 to 3, wherein R1 is ethyl, n-propyl, (: 2fluoroalkyl or -CH2CH2〇H. 6. According to the scope of the patent application A compound or a salt, wherein Ri is an ethyl group. 7. A compound or a salt according to claim 3, wherein Ri is an ethyl group. 8. A compound according to any one of claims 1 to 3 Or a salt, wherein there is a substituent or no substituent in R3. 9. A compound or salt according to item 1 of the patent application, wherein in the case where r3 is a substituted A-8 cycloalkyl group, then The substituent is: g homo group (=〇); OH; NHR21, wherein R2i is a hydrogen atom (8); -C(9)OR23, wherein 圮3 is η: hydroxyimino group (=N-OH); or (Cu alkoxy group) Imino group (=N-OR26, wherein κ26*(ν2 alkyl). 1〇· The compound or salt according to Item 1 of the patent application, wherein R3 is a substituted C:3 - s ring Next, the substituent is qh, a keto group (=〇) or a hydroxyimino group (=Ν-ΟΗ). 11 · A compound or a salt according to the scope of claim 1 wherein r3 is taken In the case of a C:3 cycloalkyl group, the substituent is a substituent at the 3-, 4- or 5-position of the R3 cycloalkyl ring (wherein the R3 cycloalkyl ring is present) The position is considered to be a point of attachment to the formula (I) or (ΙΑ) or to - ΝΗ - 12. The compound or salt according to any one of claims 1 to 3, wherein In the case of a substituted C:6 cycloalkyl group, R3 is a 3-hydroxyl-cyclohexyl 87841_960303.doc-16-283830 base (ie 3-hydroxycyclohexane+yl), 4-keto-cyclohexyl ( That is, 4-ketocyclohexanyl), 4-(imido)cyclohexyl (meaning 4-(carboxyimino)cyclohexane) or 4-((^ _2 alkoxyimine) The compound or salt according to any one of claims 1 to 3, wherein, in the case where R3 is a subgroup (aa), (4) or (cc) heterocyclic group, Then γ is 〇, NH or NC(O)methyl. The compound or salt according to any one of claims 1 to 3, wherein R3 is a subtype (aa), (bb) or (cc) In the case of a heterocyclic group, γ is 0 〇15. The compound or salt of any one of the above items, wherein R1 G is a hydrogen atom (H) or a C(0) methyl group. 16. A compound or salt according to any one of claims 3 to 3 Wherein in the case where R3 is a subgroup (aa), (bb) or (cc) heterocyclic group, then R3 is a subgroup (bb) heterocyclic group, and ηι is 1. 17_According to the application The compound or salt of any one of clauses 1 to 3, wherein in R3, the heterocyclic group of the formula (aa), (bb) or (cc) is unsubstituted (wherein Y is In the case of NR1G, rig is not classified as a substituent). The compound or salt according to any one of claims 1 to 3, wherein when R3 is a heterocyclic group of the formula (aa), γ is 〇, s, s〇2 or NH, When R3 is a heterocyclic group of the formula (bb), and R1 is not a methyl group or an ethyl group. 19. The compound or salt according to item i of the patent application, wherein R3 is a heterocyclic group of the subtype (bb), ^ is 丨, and ¥ is 〇 or ^10, which is 87841-960303.doc - 17- 1283678 wherein R1G is Η, c(o)nh2, c(o)methyl or c(o)-cf3, wherein in R3, the heterocyclic group of the subtype (bb) is unsubstituted (wherein In the case where Y is NR1G, R1G is not classified as a substituent); or R3 is a substituted C6 cycloalkyl group and is: 3-hydroxy-cyclohexyl (ie 3-hydroxycyclohexane-1-yl) , 4-keto-cyclohexyl (ie 4-keto-cyclohexane-1-yl), 4-(hydroxyimino)cyclohexyl (ie 4-(hydroxyimino)cyclohexane-b Or a compound or a salt according to any one of claims 1 to 3, wherein NHR3 is a subtype (4), (e), (f), (g), (gl), (g2), (g3), (g4), (h), (1), 1, (k), (kl), (L), (m), (ml), (m2 ), (m3), (n), (〇), (〇1), (〇2), (〇3), (〇4), (〇5), (p), (pi), (p2) , (p3), (p4), (p7) or (p8), wherein the NHR3 group is attached to the formula (I) or (ΙΑ) or (IB) pyrazole The pyridine 4-position-ΝΗ-joining point is underlined: 87841-960303.doc -18 - 1283678 (〇1) (〇2) (o3) (〇4) (〇5) 21. The compound or salt according to item 20 of the scope of the patent application, wherein NHR3 is subtype (d), (4), (f), ( G4), (h), (1), G), (k), (kl), (L), (m), (ml), (m2), (m3), (8), (6), (ol), (o2 ), (o3), (o4), (o5), (p), (p2), (p3^(p7). 22. A compound or salt according to item 20 of the patent application, wherein NHR3 is a subtype (4) , (e), (f), (8), (i), G), (8), (m), (ml), (6), (〇), (〇1) or (6). 23. A compound or salt according to claim 21, wherein NHR3 is subtype (h), (1), (j), (k), (ml), (m2), (6), (〇), (〇 2), (〇3) or (p2). 24. A compound or salt according to claim 21, wherein NHR3 is a subtype (h), (k), (8), (6) or (〇2) 〇 25. a compound according to claim 20 or a salt wherein R3 is tetrahydro-2H-piperidin-4-yl; that is, NHR3 is a subtype (h). 26. A compound or salt according to claim 1 wherein X is NR4R5. 27. A compound or salt according to claim 26, wherein R3 is tetrahydro 87841-960303.doc -19- 1283678 -2H-piperidin-4-yl; that is, NHR3 is subtype (h):-. v (h) 28. A compound or salt according to claim 27, wherein R1 is ethyl. 29. A compound or salt according to claim 2, wherein X is NR4R5. 30. A compound or salt according to item 3 of the patent application, wherein X is NR4R5. 31. A compound or salt according to claim 30, wherein R1 is ethyl. 32. A compound or salt according to item 19 of the scope of the patent application, wherein it is also a compound or a salt according to claim 32, wherein Ri is an ethyl group. 34. A compound or salt according to any one of claims 1 to 3, 6, 7, 9, 1 , η, 19 or 26 to 33, wherein R 5 is: ci-8 alkyl; Cl - 3 Fluoroalkyl; C3-8 cycloalkyl (unsubstituted); unsubstituted -(CH2)n4-C5-6 cycloalkyl, wherein η4 is 1 or 2; h wherein η5 is 2 or 3, and each The substituent Rii, independently of any other R11 substituent present, is (^-4 alkoxy, -NR15-C(9)-NH-R15 or -15 捣Ri 6 ; or -(CH 2 ) nn -CXCOR16 ; -( CH2)n 12 _C(0)NR12 Rl 3 ; -(cH2 )n12 -C(0)0R16 ; -(CH2 )n12 -S°2 -NR12 R13 ; -(CH2 )n 12 -S〇2 R1 6 • , or -(CH2)n12-CN, where n11 is 1 or 2, and ni2 is i or 2. 35. According to the scope of the patent application, i- to 3, 6, 7, 9, 10, 11, 19 or 26 to 33 A compound or salt according to any one of the preceding claims, wherein R5 is _(CH2)n13-Het, η13 87841-960303.doc -20- 1283678 is 〇, 1 or 9, tl ττ » and Het is 5- or 6-member a saturated heterocyclic ring comprising a compound selected from the group consisting of ο and π, wherein the carbocyclic ring in Het is unsubstituted. 36. According to the patent application No. 1 to 3, 6, 7, 9, 1 A compound or a salt of any one of 〇, u, 19 or 26 to 33, wherein r5 is phenyl, optionally substituted by - or two of the following groups: a functional atom; an alkyl group; a CM fluoroalkyl group; h alkoxy; trifluoromethoxy; Ci 2 alkyl sulfoalkyl-S〇2_); (: 2 alkyl § § 〇 2 _ win; r7r8n s 〇 2 _; r7r8n c 〇 _ ; NR15-C(0)Ri 6 ; r7rsn . 〇H. Q-2 alkoxymethyl; C^2 alkyl S〇2-CH2_, cyano (CN); or phenyl, optionally as a fluorine group, a Ck alkyl group, a Cl fluoroalkyl group, a C1 _2 alkoxy group or a fluoroalkyl alkoxy group. 37. A compound or salt according to claim 36, wherein the fluorenylphenyl group is optionally taken. Two of the following groups are substituted: from an atom, an alkyl group, a trifluoromethyl group, a c a 2 alkoxy group, a trifluoromethoxy group, a R7R8N_s〇2_, a r7r8n_c〇_ or a Ci-2 alkyl group-S〇2-. 38. A compound or salt according to any one of claims 1 to 3, 6, 7, 9, 10, 11, 19 or 26 to 33, wherein R5 has the formula (8) or (y) or (yl) Or (z). 39. A compound or salt according to any one of claims 1 to 3, 6, 7, 9, 10, 11, 19 or 26 to 33 wherein R5 has the formula (X). 40. A compound or salt according to item 38 of the patent application, wherein n = i, m = 1, and r = 1 〇 41. According to the patent claims 1 to 3, 6, 7, 9, 10, 11, 19 Or a compound or salt of any one of items 26 to 33, wherein in the subtypes (8), (9) and (yl): no or one or two of A, B, D, E and F are nitrogen; no or one, 87841 -960303.doc -21- 1283678 Two or three A, B, D, E and F are (: poly 6; while the remaining A, B, D, E and F are CH. 42. According to the scope of claim 41 a compound or a salt, wherein in the subtypes (8), (y) and/or (yl), none or one of A, B, D, E and F is nitrogen. 43. According to the scope of claims i to 3, 6 a compound or salt of any one of clauses 7, 9, 1 , U, 19 or 26 to 33, wherein in the subtypes (χ), (y), (yl) and (8), each R6, and the presence thereof Irrespective of any other r6, is a fluorine, gas, desert or halogen atom 'or methyl, ethyl, n-propyl, isopropyl, decyl 4, trifluoromethyl, -CH 2 〇 H, methoxy Ethoxy, q-fluoroalkoxy, OH, (V3 alkyl s(0)2_, (:3 alkyl S(0)2-NH - ' Me2N-S(0)2-, H2N-S(0)2-, -CONH2, -CONHMe, -C02H 'Cyano (CN), NMe2, T-butoxymethyl or Ci-3 Base s(o)2-ch2-. 44. A compound or salt according to claim 43 of the patent application, wherein in the sub-formula (8) '(y), (yi) and/or (Ζ), each R6, and Any other R6-independent 'as a fluorine, chlorine or adipose atom, or methyl, ethyl, n-propyl, isopropyl, trifluoromethyl, -CH2〇H, methoxy, difluoromethoxy Base, methylsulfonyl, methyl-so2_nh_ or methyl-S02-CH2·. 45. According to the scope of patent application No. 1 to 3, 6, 7, 9, 10, 11, 19 or 26 to 33 A compound or salt of any one, wherein r5 is a subfamily (χ) and is: benzyl, (monoalkyl-phenyl)methyl, [mono(fluoroalkyl)-phenyl]methyl, ( Monodecylphenyl)methyl, (monoalkoxyphenyl)methyl, [mono(fluoroalkoxy)-phenyl]methyl, [mono(indole, fluorenyl-dimethylamino)- Phenyl]methyl, [mono(methylphenyl)methyl, [mono(methyl-SCV)-phenyl]methyl/(dialkyl-phenyl)methyl 87841-960303.doc -22- 1283678, (monoalkyl· Nonylphenyl)fluorenyl, [mono(fluoroalkyl)-mono-phenyl]methyl, (di-phenylphenyl)methyl, (di-yl-monoalkyl-phenyl)methyl, [Di-yl-mono(#imethyl)-phenyl]methyl or (dialkoxy-phenyl)methyl. 46. A compound or salt according to claim 45, wherein RS is: (mono-Cu alkyl-phenyl)methyl; (mono-C fluoroalkyl-phenyl)methyl; (mono-2-alkoxy- Phenyl)methyl; [mono(C! fluoroalkoxy)-phenyl]methyl; (di-Ci2-alkyl-phenyl)methyl; (mono(^_2alkyl-mono-phenyl)) Methyl; (didecyl phenyl) fluorenyl; (di-yl mono ci -2-alkyl-phenyl)methyl; or [dihalo-mono-indenyl)-phenyl]methyl. 47. A compound or salt according to claim 46, wherein r5 is (4_c^ phenyl-phenyl)methyl; (4-Q fluoroalkyl phenyl) methyl; (4-Ck alkane) Oxy-phenyl)methyl; (4-Q-fluoroalkoxy-phenyl)methyl; (3,4-dimethyl-phenyl)methyl; (2,4-dimethyl-benzene Methyl); (3,5-dimethyl-phenyl)methyl; (2,3·dimethyl-phenyl)methyl; (2,5-dimethyl-phenyl)methyl; (4-methyl-3-chlorophenyl)methyl; (3-methyl-4-chlorophenyl)methyl; (2-methyl-4-chlorophenyl)methyl; (2-chloro) _4·fluorophenyl)methyl; (2,4-difluorophenyl)methyl; (4-bromofluorophenyl)methyl; (4-chloro-2-fluorophenyl)methyl; (3,4·dichloro-phenyl)indenyl; (2,4-dichloro-phenyl)methyl; (2,6-dichloro-phenyl)methyl; (2,3-dichloro- Phenyl)methyl, (2,4-dichloro-6-methyl-phenyl)methyl; or [2,3-dioxan (methyl)-phenyl]methyl. 48. A compound or salt according to any one of claims 1 to 3, 6, 7, 9, 1 , 11 , 19 or 26 to 33 wherein r 5 has the subtype (z), 1 &lt;is i, no or one of j, l, M or Q is CR6, and if one of j, L, M or Q is CR6, then R6 is methyl or c! fluoroalkyl, and R9 is a hydrogen atom (H) or 87841-960303. Doc -23 - 1283678 Methyl. 49. A compound or salt according to claim 45, wherein R1 is ethyl and X is NR4R5 〇 50. A compound or salt according to claim 40, wherein R1 is ethyl and X is NR4R5 〇51_ according to the compound or salt of claim 1 of the patent application, which is: 1-ethyl-4-(tetrahydrogen) _2H-pyran-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester, 4·[(1-methylhexahydropyridyl)amino group -1 -ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester, 4-[(1-ethylhydrazinohexahydropyridin-4-yl)amino]-1 -ethyl-1H-pyrazolo[3,4hepta]pyridin-5-carboxylic acid ethyl ester, 1-methyl-4-(tetrahydro-2H-bromo- 4-ylamino)-lH-pyridyl Ethylzolo[3,4-b]pyridine-5-carboxylate, 1-ethyl-4-[(3S)-tetrahydrofuran-3-ylamino]-1H-pyrazolo[3,4-b Pyridine-5-carboxylic acid ethyl ester, 1-ethyl chloro[(3R)-tetrahydrofurylamino]·1Η·pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester, 1-B Base ice (tetrahydro-2H-thiopiperazin-4-ylamino)-1Η-pyrazolo[3,4_1 small pyridine-5-rebel acid, 1·ethyl ice (tetrahydrofuran) -3-ylamino))ih-pyrazolo[3,4hepta]pyridin-5-carboxylic acid ethyl ester, 4-(cyclopropylamino)ethylidene-1H-pyrazolo[3,4_b]pyridine- 5-carboxylic acid ethyl ester, 4_[(1,1-di) Tetrahydrofurfuryl pyrimidin-3-yl) amino] ethyl - [mu] -1H- pyrazolo |; 3,4- seven] pyrazol 87841-960303. Doc •24- 1283678 ethyl 5-pyridinecarboxylate, 4-[(1,1-dihydrotetrahydro-2H-thiopiperidinyl)amino]]ethylethyl-1H-pyrazolo[3 , 4-b]pyridine-5-carboxylate ethyl ester, N-benzyl small ethyl bucket (tetrahydro-2H-piperidinylamino)·1Η_pyrazolo[3,4 aspirin-5 -Procarbamide, 1-ethyl-indole-(4-fluorophenyl)-4·(tetrahydro-2-indolyl-4-ylamino)·Η-pyrazolo[3,4-b&gt; Bishen-5-carbamamine, N-cyclopentyl-1-ethyl-4-(tetrahydro-2H&gt; decyl-4-ylamino)-1 Η-pyrazolo[3,4-b] Pyridine-5-formamide, 4-[(1-ethylhydrazinhexahydropyridin-4-yl)amino]_N-cyclopentylethylethyl-1H-pyrazolo[3,4-b] p-Phase-5-formic acid amine, 1-ethyl-N heptaidine-4-ylmethyl)_4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3 ,4-b]external b-position-5-formamide, 4-[(1-ethylhydrazinylhexahydropyridin-4-yl)amino]-N-benzyl-1-ethyl-1H-pyrazole And 3,4-b]p than yt-5-carbamide, 1-ethyl-N-(2-ethylbutyl)-4-(tetrahydro-2-indole-pyran-4-ylamine Base)-1Η-pyrazolo[3,4-b]p ratio -5-5·carbamamine, 1-ethyl-N-(2-ethylbutyl)_4-[(1-methylhexahydro) Pyridin-4-yl)amino]-1H-pyrazole And [3,4-7]pyridine-5-formamide, 4-[(1_ethinylhexahydropyridin-4-yl)amino]_1_ethyl-oxime (2-ethylbutyl) _1H-p-pyrolo[3,4-pyridinium-5-carboxamide, 1-ethyl-N-(4-fluorophenyl)-4-[(1-methylhexahydropyridin-4-yl) Amino]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, 4-[(1-ethyl-based acicular π-precipitate-4-yl)amino]-1- Ethyl-N-(4- gas benzene·base ratio 87841-960303. Doc -25- 1283678 oxazo[3,4-b]pyridine-5-carboxamide, 1-ethyl-N-n-propyl-4-(tetrachloro-211-0 butyl _4*·yl Aminopyrazine[3,4-b]pyridine-5-carboxamide, 4-[(1-ethenylhexahydropyridin-4-yl)amino]_1_ethyl-n-propyl-1H- Pyrazolo[3,4-b]pyridine-5-carboxamide, N-yl-1_1-ethyl-4-[(l-methylhexahydrop-buty-4-yl)amino]_1Η_ρ More than tons of [3,4-b]pyridine-5-formamide, 4-[(1-ethylhydrazinium hexahydropyridin-4-yl)amino]_1_ethyl-N-indenyl pyridine ·Methyl-)-Η-pyrido[3,4-b]external b-position-5-carbamamine, N_yryl-1-methyl-4-(tetrahydro-2H- shouting-4 _ ylamino group bite and [3,4_b] mouth bite -5-carbamamine, N-(2-ethylbutyl)·1-mercapto-4-(tetrahydro-2H-t trace- 4-aminoamino)-1Η-external b ton[3,4-b]p than ammonium-5-formic acid amine 'N-(4-fluorophenyl)·1-methyl_4-(tetrahydro- 2H_piperazin-4-ylamino)-1Η-pyridox[3,4-b]p ratio biting-5-formic acid amine 4-[(1-ethenylhexahydropyridine_4_yl) Amino]_n_benzyl-1-methyl-1H-pyrido[3,4-b]indole-5-caramin' 1-ethyl-N-methyl-4-(tetrahydro- 2H-pyran-4-ylamino)-1Η-pyrazolo[3,4_b]pyrazine-5-cartoamine, - 1_ethyl-N-ethyl_4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 1 -ethyl-N-isopropyl-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, N- Benzyl-1-ethyl_4-[(3S)-tetrahydrofuran-3-ylamino]_1H-pyrazolo[3,4-b]py 87841-960303. Doc •26- 1283678 D--5-armamamine, N-benzyl small ethyl-4-[(3R)-tetrahydrofuran-3-ylamino]-1H-pyrazolo[3,4-7]盐-5-甲含胺, N-benzyl-1-ethyl winter (tetramethylene sulfonyl-3-ylamino) Η 吡 pyrazolo[3,4_b]pyridine-5-cartoamine, N-爷基·4-[(1,1-dihydrotetramethylene sulfonyl-3-yl)amino]-indole·ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide , N-Mercapto-4·[(1,1_dihydrotetrahydrothiopyranyl)amino]]ethylethyl-1Η-pyrazolo[3,4-b]pyridine_5_ formazan Amine, N-benzyl-1-ethyl-4-(tetrahydro-2H-thiopiperazin-4-ylamino)-1Η·pyrazolo P,4-b]pyridine-5-carboxamide , 1-ethyl-N-(4-fluorophenyl)-4_[(3S)·tetrahydrofuran-3-ylamino]_1H-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl_N-(4-fluorophenyl)_4-[(3R)_tetrahydrofuran-3-ylamino]-1H-pyrazolo[3,4-b]p Amine, 1-ethyl-N-(4-fluorophenyl)-4-(tetrahydro-2H-thiopiperan-4-ylamino)-1Η·pyrazolo[3,4-b]pyridine -5-Mergamine, 1_ethyl-N-(4-fluorophenyl)-4·(tetrahydropyrimidin-3-ylamino)-1Η-pyrazolo[3,4-b] p Bishen-5-cartoamine, 4-[ (1,1-dihydrotetrazole-3-yl)amino]_1_ethyl·ν_(4-fluorophenyl)_1H-pyrido[3,4-b]p than lake-5- Methionamine, 4-[(1,1·tetrahydro-2H-thiopyran-4-yl)amino]-1-ethyl-N-(4-fluorophenyl)-1Η· b峻和[3,4-b]p 比淀-5_carbamamine, 1-ethyl·Ν-[4-(methylsulfonyl)-yl]_4_(tetrahydro-2Η_pipefi-4 -ylamino)-1Η_ 87841-960303. Doc •27- 1283678 Pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-N-[3-(methylsulfonyl)-yl]-4-(tetrahydro-2H -piperazin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(5-chloropyridin-2-yl)methyl] Radix (tetrahydro-2H-fluorenyl-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-N-[(5-A) 3-phenylisoxazol-4-yl)methyl]-4-(tetrahydro-2H-piperidin-4-ylamino)_1H-pyrazolo[3,4_b]pyridine_5_A Indoleamine 'N-(2-Terti-butoxyethyl)-1-ethyl-4-(four-rat-2H-pyran-4-ylamino)-1Η_Exo I: oxazo[3, 4-b]pyridine-5-carboxamide, 1-ethyl-4-(tetrahydro-2H-piperidin-4-ylamino)-indole-(1,3-pyrazol-2-ylmethyl) )-1Η-pyrazolo[3,4-b]pyridine-5-formamide, 1_ethyl-N_(p-melt-4-ylmethyl)-4·(four gas-2H_ shouting -4-ylamino)·1Η-ρ is more than [3,4-b]pyridine-5-formamide, 1-ethyl-Ν·[(2_methyl_l,3-p _4_yl)methyl]-4-(tetrahydro-2Η·»-s--4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, N- [3-(Tertibutoxymethyl)octyl]-1-ethyl-4-(tetrahydro-2H-l-butan-4-yl Amino)-1H-pyrazolo[3,4-b]pyridine·5-carboxamide, 1-ethyl-hydrazine-{2_[methyl(methylylidene)amino]ethyl}-4 -(tetrahydro-2-indole-pyran-4-ylamino group is more than [3,4-b] bamboo b-precipitate-5-cartoamine, 1-ethyl--2-ylmethyl)-4- (Tetrahydro-2Η-Ϊ派喃-4_ylamino-amino-[3,4-b]ex-b-butyl-5-cartoamine, N-(2-chloro-6-fluoroyl) 1-ethyl-4-(tetrahydro-2-indole-scarred-4-ylamino)-1Η-exo 1: oxazolo[3,4-b]ppyridin-5-carbamamine, 1 -ethyl-N-[(6-keto-1,6-dihydrofolate b-butyl-3-yl)methyl]_4_(tetrachloropyran_4_ 87841-960303. Doc -28- 1283678 arylamino)-1 Η-pyrazolo[3,4-b]pyridine-5-carboxamide, N-[3-(aminocarbonyl)indolyl] small ethyl-4-( Tetrahydro-2H-piperazin-4-ylamino)-1Η-峨君[3,4-b>pyramid-5-carbamide, 1-ethyl-N-{4-[(methylamine) Base) phenyl}-4-(tetrachloro-2H-peak-2-ylamino)-1Η-pyrazolo P,4_b]pyridine·5·carbamidine, 1-ethyl-hydrazine -[2·(1_methyl-1Η·imidazol-4-yl)ethyl]ice (tetrahydro-2-indole-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b] Pyridin-5-carbamamine, N-{2-[(Tetralamyl)amino]ethyl}_1_ethyl-4-(tetrachloro-2H-bromo- 4-ylamino)- 1Η-pyrazolo[3,4-b]pyridine-5-formamide, 1-ethyl-N-(1H-tetrazol-5-ylmethyl)_4-(tetrahydro-2-indole·pyran 4_ylamino)-1Η-exo-bazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-4-(tetrachloro-2H-pyran-4-ylamino) ·Ν-[2-(1Η-1,2,4-Trisyl-1_yl)ethyl]-1Η·pyrazolo[3,4-b]pyridine-5-formamide, 1-ethyl -4_(tetrachloro-211-0 succinyl-4 ylamino)_N-[4_(trifluoromethyl)phenyl]-1H-external bww and P,4-b&gt; Amine, 4-({[1-ethyl-4-(tetrahydro-2Η_^)-4-ylamine )-1Η-ρ is more than [3,4_b]p than biting •5-yl]carbonyl}amino)hexahydropyridine-1-carboxylic acid tert-butyl ester, 1-ethyl_N-{3- [(甲), Amino] propyl}-4-(tetrahydro-2H· shouting 4·ylamino)-1Η_ρ 比吨[3,4七&gt; 比淀-5-甲醯Amine, Ν-[2-(dimethylamino) aryl]-1-ethyl-4-(tetrahydro-2 Η-喊 _ _4_ ylamino)-1 Η-carbazolo[3,4- b]pyridine-5-carboxamide, 1-ethyl-N-[(1-ethyltetrahydropyrrole-2-yl)methyl]-4-(tetrahydro-2H-pyran-4-ylamino) )-lH&gt; than vomiting [3,4-b] leaf b-precipitate-5_cartoamine, 1-ethyl_N-(izg hydrogen sulfan-2-ylmethyl)_4_(tetrahydro-2H·喃 -4--4-ylamino)-1Η- 87841-960303. Doc -29- 1283678 Pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-N-tetrahydro-2H-pyran-4-yl-4-(tetrahydro-2H- Shoutin-4-ylamino))Η-ρ-pyrazolo[3,4-b]pyridine-5-carboxamide, N-{4-[(dimethylamino)sulfonyl]benzyl} small Ethyl-4-(tetra-argon-2H-piperazin-4-ylamino)·1Η·ρ is more than [3,4-b]^ dian-5-cartoamine, 1·ethyl-N -{3-[(methylsulfonyl)amino]benzyl}-4_(tetrahydro-2H-piperidin-4-ylamino)-1H_p is more than [3,4-b]p-precipitate- 5-mercaptoamine, 1-ethyl-N-(4-methoxyphenyl)-4-(tetraqi-2H-methane-4-ylamino)pyrano[3,4-b]pyridine- 5-carbalamine, 1-ethyl-indole-[3-(2·ketotetrahydropyrroleyl)propyl]-4-(tetrahydro-2H-pyran-4-ylamino) [3,4-b]p"b-deposition_5_cartoamine" 1-ethyl-N-[2-(l-methyltetradecylo-2-yl)ethyl]-4-( Tetranitro 2H-propan-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-formamide, 1-ethyl-N-(p-but-3-yl Methyl)-4-(tetrachloro-2H-chloropyran-4-ylamino)-1Η_ρ比比[3,4_b]pyridine-5-carbamamine, 1-ethyl-N-(l-A氲6氲)4 ))-4-(tetrahydro-2H- sher-4-ylamino)-lH-^b spit [3 , 4-b]p than yt-5. ketoamine, 1-ethyl Ν-(1-ethylpropyl) _4·(tetrazo-2 Η-» δ -4-ylamino group [3,4-b]pyridine-5-carboxamide, 1-ethyl-N-(2-hexahydrofolate b-butyl-1-ylethyl)-4_(tetrahydro-2H- britium-4-胺 ) π π π π π π 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 Tetrahydro-2Η-scaridin-4-ylamino)-1Η-pyrazolo[3,4-7]pyridine-5·carboxamide, N-(3-ethoxypropyl)ethylethyl-4_( Tetrahydro-2H-t-norm-4-ylamino)-1Η·ρ ratio Jun 87841-960303. Doc -30- 1283678 and [3,4_b]pyrazine-5-formamide, N-(cyclohexylmethyl)_1_ethyl_4-(tetrahydro-2H-piperan-4-ylamino) -1Η-pyrazolo[3,4-b]p than lake-5-cartoamine&gt; N-[3-(dimethylamino)propyl]_1_ethyl bucket (tetrahydro-2H-piperider喃-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-N-neopentyl-4-(tetrahydro-2H-pyran -4-ylamino)_1H-pyrazolo[3,4-b] oxime-5-formic acid amine 1-ethyl-N-(4-methoxybenzyl)-4-(tetrahydro- 2H-piperazin-4-ylamino)-1Η-pyrazolo[3,4-b]p than ammonium-5-formate amine 1-ethyl-N-{2-[(phenylsulfonyl) Amino]ethyl}winter (tetrahydro-2Η-piperidin-4-ylamino)-1Η_ρ is more than eaten [3,4_1&gt;&gt; bis--5-cartoamine, Ν-[2-(B Amidino)ethyl]-1_ethyl-4·(tetrahydro-2-indole-piperazin-4-ylamino)-1Η-exopurine and [3,4-b]^ than bite-5- Amine, 1-ethyl-N-{2-[(methylsulfonyl)amino]ethyl}-4·(tetrahydro-2H-pyran-4-ylamino)_1Η·ρ ratio And 3,4-b]pyridine-5-formamide, 1-ethyl-N-{2-[(2-methoxyphenyl)(methyl)amino]ethyl}-4-( Tetrahydro-2Η-piperazin-4-ylamino)-1Η·pyrazolo[3,4-b Pyridine-5-formamide, 1-ethyl-indole-(2.indolyl-2-phenylethyl)-4-(tetrazo-2H-bran-4-ylamino)-1Η_ Oxazo[3,4-b]pyridine-5-carboxamide, N-(2,5-difluoroindolyl) small ethyl 4-(tetrahydro-2H-pyran-4-ylamino) )-1Η·pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-4-(tetrachloro-2H-pyran-4-ylamino)_N_[4-(three Gas methyl) genomic]-1H-p than wow [3,4 VII] than bite-5-carbamide, N-cyclopropyl small ethyl-4-(tetrahydro-2H-pyran- 4-ylamino)-1Η-pyrazolo[3,4-b] 87841-960303. Doc -31- 1283678 Acridine-5-carbamide, N-(2-Amino-1-ketoethylethyl) (tetrahydro-2H_piperidinyl)_m_pyrazolo[3,4 -b]pyridine-5-carboxamide, 1-ethyl-N-(3-indolylphenyl)-4-(tetrahydro-2H-piperidinylamino)_1H_pyrazolo[;3 ,4-b]pyrazine_5_carbamamine, N-(3,4-difluorobenzyl)_1_ethyl_4·(tetrahydro-2H-piperidin-4-ylamino)-1Η -pyrazolo[3,4-b]p than ammonium-5-formate, 3-({[1-ethyl-4-(tetrahydro-213⁄4-an-4-ylamino)-1Η-pyrazole And [3,4-b>pyridin-5-yl]-yl}amino)propionic acid, Ν-(1·benzylhexylpyridin-4-yl)-ethyl-4-(tetrahydro) _2H-piperazin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 1_ethyl_4_(tetrahydro-2H_ shouting-4- Amino)-indole-(1,3,4-oxadiazol-2-yl)-1Η-pyridin[3,4-b>pyramid-5-carbamide, N-(2,3 -dihydro_1H-茚·2·yl)·1-ethyl_4_(tetrahydro-2H-piperidin-4-ylamino)_1Η·p is more than [3,4-b]p than olfactory -5-Acantylamine '1·Ethyl-N-[2-(2-keto-Sensage)-ethyl)-4-(tetrahydro-2H--pyran-4-ylamine -1Η-pyrazolop,4-b]pyridine-5-carboxamide, N-(3,4- Di-oxy-yl)-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide N-(3-lactyl)·1-ethyl_4·(tetrazo-2H-pyran-4-ylamino yiH-p than [3,4-b]pyrazine-5-formamidine Amine, 1-ethyl-N-(2-lightethyl)-4-(tetrazol-2H-pyran-4-ylamino)-1Η-ρ than 嗤[3,4-b]pyridyl -5-Mergamine, 1-ethyl-indole-{4.[(methylsulfonyl)methyl]phenyl}.4-(tetrahydro-2H-pentanylamine 87041-960303. Doc -32- 1283678 base)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, Ν-[3·(dimethylamino)-3-ketopropyl]-1- Ethyl winter (tetrahydro-2H.piperidin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl_N-[(1- Methyl-1H-imidazol-5-yl)methyl]-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5- Indoleamine, 1-ethyl-N-{4-[(methylamino)sulfonyl]phenyl}-4-(tetrahydro-2Η·piperidin-4-ylamino)-1Η-pyrazole [3,4-b]pyridine-5-formamide, N-(2-cyanoethyl)-1_ethyl-4-(tetrahydro-2H-piperidyl-4-ylamino)-1Η Pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-N-[(l-methyl-1H-pyrazol-4-yl)methyl]-4-(four Hydrogen-211_piperazin-4-ylamino)-1Η-pyrazolo[3,4_b]pyridine-5·carboxamide, 1-ethyl-4-(tetrachloro-2H-jum-4- Amino)-N-(2-p-cephen-2-ylethyl)-1 oxime-borazolo[3,4-b]pyridine-5-carboxamide, Ν-[2-(4· Chlorophenyl)ethyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide , 1-ethyl-N-[2-(2-methoxyphenyl)ethyl]-4-(tetrahydro-2H-piperidinylamine )-1Η-External b and [3,4-b]External ti_5_Artemis, 1-n-propyl-4_(tetrahydro-2H-piperidin-4-ylamino)-1Η -pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester, 1-(2-ethyl)-4-(tetrahydro-2Η-bran-4-ylamino)·1Η-ρ More than spit and [3,4-b]p than D--5-haloic acid brewing 'N-[4_(A))-l-n-propyl-4-(tetrahydro-2H-喃 -4- 基 基 胺 比 [ [ 3 [3,4-b]p than 嗓-5- amide, N-(4-fluorophenyl) small n-propyl-4-(tetrahydro-2 Η - keloid-4-ylamino)-1Η_ρ ratio jun and 87841-960303. Doc -33 - 1283678 [3,4-b]pyridine-5-carbamide, 1-ethylmethylmethyl-4-(tetrahydro-2H-piperidin-4-ylamino)_1 沁pyrazole Ethyl [3,4-b]pyridine-5.carboxylate, N-benzyl-1-ethyl-6-methyl-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η _pyrazolo[3,4-b]pyridine-5-carboxamide, N-benzyl-1-ethyl-4_[(2-ketoprazin-7-yl)amino]- lH-pyrazolo[3,4-b]pyridine-5-carboxamide, N-benzyl-1-ethyl-4-[(3-hydroxycyclohexyl)amino]-1H-pyrazolo[ 3,4-b]pyridine-5-carboxamide, N-benzyl small ethyl-4-[(4-hydroxycyclohexyl)amino]-1H-pyrazolo[3,4-b]pyridine- 5-carboxamide, N-fluorenylethylidene-4-[(4. ketocyclohexyl)amino]·1Η_pyrazolo[3,4-b]pyridine-5-carboxamide, 1 -ethyl-N-(2-hydroxylethylethyl)-4-(tetrahydro-2H-piperidin-4-ylamino)_1H-pyrazolo[3,4-7]pyridine_5_ formazan Amine, (2S)-2-({[l_ethyl_4-(tetrahydro-2H-piperidinyl)-1Η-pyrazolo[3,4_b]pyridin-5-yl]carbonyl} Methylamino)-3-hydroxypropionate, ethyl 1-ethyl-4-[(4-hydroxycyclohexyl)amino]·1Η-pyrazolop,4-b]pyridine-5-carboxylate , 1-ethyl-4-[(4- Ethyl cyclohexyl)amino]-1H-azolo[3,4-b]pyridine-5·carboxylate ethyl ester, 4·[(1-ethylindolyl-4-hexapyridine)amino] Ethyl 1-H-pyrazolo[3,4-b]pyridine-5-carboxylate, 4-[(4-aminocyclohexyl)amino]ethylethyl-1H-pyrazolo p,4 -b]pyridine_5·carboxylic acid 87841-960303. Doc -34- 1283678 Ethyl ester, N-[(l_oxidation_3-p ratio) methyl]-4-(tetrachloro-2H-pyran-4-ylamino)-1Η-ρ-pyrazole And [3,4-b]pyridine-5-formamide, 1-ethyl-N-[(l-oxidized-2-p-butylated) fluorenyl]-4-(tetrazo-2H- shout -4-ylamino)-1Η-ρ is more than [3,4-b]p ratio-5-cartoamine, 1-ethyl-N_[(l-oxidation-4-p ratio) Methyl]-4-(tetrahydro-2H-pyran-4-ylamino)-1Η-ρ is more than [3,4-b]p than pent-5-cartoamine, 4-[( 4-Aminocyclohexyl)amino]-1_ethyl-N-(phenylmethyl)-1Η-ρ is more than [3,4-b]pyridine-5-formamide, 1- Ethyl-4-{[(3S)-2-keto-3-tetrahydropyrrolyl]amino-based N-(phenylmethyl)-1Η-azolo[3,4-b]pyridine-5 -Procarbamide, 4-[(2,5-diketo-3-tetrahydropyrrolyl)amino]-1-ethyl-N-(phenylmethyl)-1Η-external oxime [3 , 4-b&gt; phage_5·carbamidine, 4-[(cis-4-aminocyclohexyl)amino]-1-ethyl-indole-{[4-(methoxy)phenyl ]methyl}-1Η-ρ 吨和[3,4-b&gt; bicyan-5-cartoamine, 4-[(cis-4-aminocarbamoyl)amino]-1-ethyl- N-({4_[())amino]phenyl}methyl)_1Η-ρ ratio spit [3,4-b Exo b-position-5-carbamamine, 4-[(cis-4-aminocyclohexyl)amino]-Ν·(2,3·dihydro-1H-indol-2-yl)-1-B -1H-pyrazolo[3,4-b]pyridine-5-carbamamine, 1-ethyl-N-{4-[(methylsulfonyl)methyl]phenyl}-4-[( 4-ketocyclohexyl)amino]-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(2,4-methylphenyl)methyl]-1 -ethyl-4-[(4-Steylcyclohexyl)amino]-1H_ Outocarbazolo[3,4-b]pyridine-5-carboxamide, N-[(3,4-dimethyl) Phenyl)methyl]sodiumethyl 4-[(4-ketocyclohexyl)amino]-1H- 87841-960303. Doc -35· 1283678 外匕君[3,4-b]pyridine-5-carbamimidamine, N-[(3,4-dichlorophenyl)indolyl]-1-ethyl_4_[(4 _嗣-cyclohexyl)amino] ΐΗ-ρ ratio ♦ [3,4-b]pyridine-5-methanamine, 1-ethyl-N-{[4·(methoxy)phenyl] Methyl b 4_[(4-ketocyclohexyl)amino]-1H-exoquinone [3,4-7]pyridine-5-carboxamide, 1-ethyl-N-({4-[( Methanesulfonyl)amino]phenyl}methyl)-4-[(4-ketocyclohexyl)amino]-ΙΗ-ρ is more than [3,4_b]p than ammonium-5-formate, N-{[4-(dimethylamino)phenyl]methyl}methylethyl-4-[(4-ketocyclohexyl)amine group is more than spit [3,4-7] than dian-5- Methionamine, N-({4-[(difluoroindolyl)oxy]phenyl}methyl))ethylethyl-4-[(4-ketocyclohexyl)amino]-1H-pyrazole [3,4-7]pyridin-5-carbamide, 1-ethyl-4-[(4-ketocyclohexyl)amino]-N-{[4-(trifluoromethyl)phenyl ]methyl}-1Η-ρ is more than [3,4-b> butyl--5-formic acid amine, 1-ethyl-N-{[4-(methylphenyl)phenyl]fluorenyl}- 4-[(4-Ketylcyclohexyl)amino]-1Η-pyrido[3,4-b]pyridine-5-carboxamide, 1-ethyl-anthracene (4-fluorophenyl)- 4-[(4-ketocyclohexyl) Amino]-1H-pyrazolo[3,4-b]pyridine_5-formamide, 1-ethyl·4·[(4-ketocyclohexyl)amino]-indole-(2·pyridine Methyl)-iH-pyrazolo[3,4-b]p than lake-5-caraamine trifluoroacetate, N-(2,3-dihydro-1H· although-2-yl) 1-ethyl-4-[(4-ketocyclohexyl)amino]-iH-p is also a ratio of [3,4-b]pyridine-5-carboxamide, N-(l-ethenyl- 4-hexahydropyridyl)-1-ethyl-4-[(4-ketocyclohexyl)amino]-1Η-ρ than oleno[3, 'b] outer 1: lake-5-carboxamide , 1-ethyl-N-[(l-methyl-1Η_ρ 咬-4-yl)methyl]-4-[(4-fluorenylcyclohexyl)amine 87841-960303. Doc -36- 1283678 ]-1Η-峨君[3,4-b]pyridine-5-carbamimidamine, N,l-diethyl_4_[(4-ketocyclohexyl)amino]-1H -pyrazolo[3,4-b]pyridine_5_carbamidamine, 1-ethyl-4-[(4,ylcyclohexyl)amino]-N_(1,3-pyrazole-2-yl) Base)_1H_pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl(phenylmethyl&gt;4-(tetrahydro-2H-piperazol-3-ylamino) ·1Η·pyrazolo[;3,4-b]pyrazine-5-formamide, N-({4-[(difluoromethyl)oxy]phenyl}methyl)succinyl winter ( Tetrahydro-2fanipan-3-ylamino)-1Η-pyrazolo[3,4_b]pyridine-5-carbamimid, 1-ethyl-4-(tetrahydro-2-indolyl_3 —N-amino]-N-{[4-(trifluoromethyl)phenyl]methyl}-1Η-pyrazolo[3,4-b]pyridine-5-formamide, 1-ethyl- N-{[4_(methylsulfonyl)phenyl]methyl}·'(tetrahydro-2H-piperidin-3-ylamino)-1Η-ρ than gorge[3,4_b]p ratio- 5-mercaptoamine, 1_ethyl-N]4·[(methylsulfonyl)methyl]phenyl}_4-(tetrahydro-2H-pyranyl-3-ylamino)-1Η-ρ ratio并[3,4-b] bite-5-carbamamine, 1-ethyl-N-(4-fluorophenyl)-4-(tetrahydro-2-indolyl-3-ylamino) -1Η-pyrazolo[3,4-b]pyridine-5-decylamine 1-ethyl-indole (2-pyridine-1-yl)-4-(tetrahydro-2-indol-3-ylamino)_1H-p-pyrazolo[3,4-b]pyridine-5-carboxamide Trifluoroacetate, Ν-(2,3·dihydro-1H-茚·2_yl)&gt; 1-ethyl ice (tetrahydro JH-pyran-3-ylamino)-1Η-p [3,4-b]External 1: Bite-5-carbamamine, N_indolyl-4-hexahydropyridyl&gt;1·Ethyl 4-(tetrahydro-2H-slightly-3 -ylamino)-1Η-ρ ratio 并[3,4-b]external b-position-5-carbamamine, 1-ethyl-N-[(l-methyl-1H4 salivyl)methyl ]·4_(tetrahydro-2H piperidinylamine 87841-960303. Doc • 37 · 1283678 base)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, N,l-diethyl-4-(tetrahydro-2H- britylene·3-yl Amino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-4-(tetrahydro-2H-piperidin-3-ylamino)-indole-( 1,3-pyrazol-2-ylmethyl)_1H-leaf sulphate [3,4-b]p than yam-5-carbamamine, 4-[(1-ethyl-bromo-4-hexa-nitro-p ratio Amyl)-amino]-N-(2,3-dinitro-1H-indol-2-yl)-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide , 4·[(1·乙牛基-4_:ττ氯1 (7 症基基) Amino]_N-[(3,4-dilactosyl)methyl]-1·ethyl-1H-pyridyl Zymbly p,4-b]pyridine-5-carboxamide, 4-[(1-ethylindolyl-4-hexahydropyridinyl)amino]-1-ethyl-N-[(3-fluorobenzene) Methyl]-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 4-[(1-ethylhydrazine) hexahydropyridinyl]-anthracene-[(3 ,4·difluorophenyl)methyl]sodiumethyl-1Η-Ρ than spit[3,4-b]p than ammonium-5-formate, 4-[(1-ethylindol-4-6 Hydropyridyl)amino]-N-[(2,5-difluorophenyl)methyl]-1-ethyl-lH-p than spit[3,4-b]p than pent-5-A Amine amine, 4-[(1·ethyl-brown chlorine p-butyl group) amine group]·1-ethyl-Ν-{[3·( Tris-methyl)phenyl]methyl}-1Η-pyrazolo[3,4-b]pyridine-5-formamide, 4_[(1_ethinyl-4)hexahydropyridyl) ]-1-ethyl-Ν·{[4-(trifluoromethyl)phenyl]methyl}·1Η-ρ ratio spitting [3,4-7] than precipitation _5_cartoamine, 4_[ (1_Ethylidene_4_hexahydropyridyl)amino]·Ν·[(2,6-difluorophenyl)methyl]+ethyl_1Η_external b][3,4-b ]p-precipitate-5-cartoamine, 4-[(1-acetoxy-4-hexahydrop-decyl)amino]-N-[(3-chlorophenyl)methyl]_ι·ethyl -1H-pyrido[3,4-b]exo b-pyridine-5-carboxylate, 4·[(1-acetoxy-4-hexahydro-b-)amino]-1-ethyl-fluorene -{[4-(decyloxy)phenyl] 87841-960303. Doc -38- 1283678 methyl}-1Η-pyrazolo-; 3,4-b]pyridine-5-carbamimid, 4-[(1-ethylindenyl-4-hexahydropyridinyl)amino] 1-ethyl-N-[4-(methoxy)phenyl]-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 4-[(1-ethenyl- 4-hexahydropyridyl)amino]-N-({4-[(dimethylamino) hydrazino]phenyl}methyl)-1-ethyl-1H-pyrazolo[3,4- b]pyridine-5-carbamamine, ethyl 4-phosphoryl p-pyrifosyl)amino]-1-ethyl-N-(l,2,3,4-tetrahydro-1-yl )-1Η-β is more than gorge [3,4-b&gt; bis--5-carbamamine, 4-[(1-ethylindolyl_4-hexahydropyridinyl)amino]-N_{[2- (dimethylamino)phenyl]fluorenyl}small ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, 4-[(1-ethyl aryl 4-ch^) Chlorine p ratio aryl)amino]-N-[(2,4-dichlorophenyl)methyl]-1-ethyl-1H-pyrazolo P,4-b]pyridine-5-carboxamide , 4-[(1-ethylindolyl-4·hexahydropyridinyl)amino]ethylidene-N-[(2-fluorophenyl)methyl]-1Η-pyrazolo[3,4-b Pyridine-5-formamide, 4-[(1-acetoxy-4-hexahydroindole b-butyl)amino]-indole-[(2-carbyl-6-fluorophenyl)methyl]- 1_Ethyl-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 4-[(1-acetamidine) -4_hexahydropyridyl)amino]-N-({4-[(difluoromethyl)oxy)phenyl}methyl)-1-ethyl-1H-pyrazolo[3,4- b]pyridine_5_decylamine, 4·[(1-acetoxy-4-hexahydrofolate b-aryl)amino]-N-{[3-gasyl (methoxy)phenyl] A 1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carbamimidyl, 4-[(1-ethylindolyl-4-hexahydropyridinyl)amino] -[(5-carbyl-2-pyridyl)methyl]-1-ethyl-1Η-0-pyrazolo-; 3,4-b]pyridine-5-carbamamine, 4-[(1- Ethyl-4-pyridinyl)amino]-N-(5-chloro-2,3-dihydro-1H_^_2_yl H-ethyl-1H-pyrazolo[3,4-7] Pyridine_5_formamidine, 4-[(1-acetoxy-4-atomium nitrogen-pyridyl)amino]-1_ethyl-N-(l,3-p-Sen_2• base 87841-960303. Doc -39- 1283678 base)-1Η-pyrazolo[3,4-b]pyridine-5-methanamine, 4-[(1-ethylindolyl-4-hexahydropyridinyl)amino] Ν-Ν_{[4·(Methanesulfonyl)phenyl]methylindole-pyrazolo[3,4-b]pyridine-5-carboxamide, 4-[(1-ethenyl-4- Hexahydropyridyl)amino]-indole·(2,2-diphenylethyl)-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, 4- [(1_Ethyl-4-pyridinyl)amino]-1-ethyl-N-({4-[(methylsulfonyl)amino]phenyl}methyl)_1H-pyrazole And [3,4-b]pyridine-5-formamide, 4-[(1-ethylindenyl hexahydropyridinyl)amino]ethylidene-Ν·({4-[(methylamino)) Carbonyl]phenyl}methyl)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 4-[(1-ethylindolyl-4'hexahydropyridinyl)amino]- Ν_{[4·(Aminosulfonyl)phenyl]methyl}small ethyl _lHw is more than [3,4-b]pyridine·5·carbamamine, 4-[(1-acetamidine) _4_hexahydropyridyl)amino]_1·ethyl-indole-({3-[(methylamino)carbonyl)phenyl}methyl)-1Η-pyrazolo[3,4-b] Pyridine-5-formamide, 4-[(1-ethylindolyl-4-hexahydropyridinyl)amino]-N-{[4-(aminocarbonyl)phenyl]methyl}methyl} 1Η·pyrazole And [3,4-b]pyridine-5-formamide, 4-[(1-ethylindolyl-4-hexahydropyridinyl)amino]-1-ethyl-Ν·{[6-(A Oxy)-3-pyridyl]methyl}-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-N-4-hexahydro outside 1: decyl- 4-(tetrahydro-2H-fluoren-4-ylamino)-1Η-β is more than ton[3,4-b]pyridine-5-carboxamide, 1-ethyl-N-(4-hexa) Hydropyridylmethyl)-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-p than spit [3,4-b]pyridine-5-carbamidamine, 1-B --N-[l-(ethyl continuation)-4-hexahydro outside 1: decyl]-4·(tetrahydro-2H-bran-4-ylamino)-1Η-pyrazolo[ 3,4-b]pyridine-5-carboxamide, 1-ethyl-N-{1_[(1-methylethyl) hydrazino] winter hexahydropyridyl-4- 4-tetrahydro-2H- 87841-960303. Doc -40- 1283678 Piperazin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, N-[l_(cyclopentylsulfonyl)_4_6 Hydropyridyl]-1·ethyl-4-(tetrahydro-2H-indol-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 1- Ethyl-N-[l-(methylsulfonyl)-4-hexahydropyridyl]-4-(tetrahydro-2H-piperidinylamino)·1Η-pyrazolo[3,4_b]pyridine 5-5-carbamamine, 1-ethyl-indole-{1-[(phenylmethyl)sulfonyl]-4-hexahydropyridinyl}-4-(tetrahydro-2H-piperidinylamine Base)-1Η_pyrazolo[3,4_b]pyridine-5-formamide, 1-ethyl-N-[l-(phenylsulfonyl)-4-hexahydropyridyl]-4-(four Hydrogen-2H-piperazin-4-ylamino)_1H-pyrazolo[3,4-b]pyridine-5-carbamimid, I-ethyl-oxime [1-(propyl acid) 4--4-hexachloro-b-butyl]-4-(tetrachloro-2H-17-endan-4-ylamino)_1H-pyrazolo[3,4_b]pyridine-5-carboxamide, Ν-[ 1·(cyclopropylcarbonyl)donghexahydropyridyl]sodiumethyl 4-(tetrahydro-2H-pyran-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine- 5-carbalamine, 1-ethyl-indole-[1-(3·furylcarbonyl)-4-hexahydropyridinyl]-4-(tetrahydro-2H-piperidin-4-ylaminopyridinium And [3,4-b]p than the lake -5-Artemisamine, Ν-[1·(3,3·dimethylbutanyl)_4_hexafluoropyridyl]-1-ethylyl (tetrahydro-2H-pyran-4-ylamino) Η 吡 · pyrazolo[3,4-b]pyridine-5-formamide, 1-ethyl-N-[l-(2-ethylbutyryl)-4-hexachloro-b-butyl]- 4-(tetrachloro-2H-bromo-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carbamimidamine, N-[l-(p-amylethyl) )-4-hexachlorop ratio benzyl]-1-ethyl-4-(tetrazine-2H-bungan-4-ylamino)-1Η-ρ ratio ton[3,4-b]p ratio盐-5·甲甲胺' 1-Ethyl-N-[l-(2-methylpropionate)·4-ττ卩卩 ratio]-4-(tetrazo-2H_旅喃-4 -Amino group ratio bite [3,4-b]p than lake-5-cartoamine, 1 ·ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-Ν-[ 1-(tetrahydro-2H- shouting-4_ base talk-41 - 87841-960303. Doc 1283678 yl)-4-hexahydropyridyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethylpropanyl group, 4-ττ chloropyranyl -4-(tetrasanosyl-4-ylamino)-1Η-pyrazolo[,3,4-b]pyridine-5-carboxamide, N-[1-(N-ethinylamine) Indenyl)-4_hexahydropyridyl]-1-ethyl-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[;3,4-b]pyridine- 5-Mercaptoamine, 1-ethyl-N_[l-(4-moffyl-ethyl)-4-hexachloro-p-butyl]-4-(tetrazine-2H-pyran-4- Amino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-fluorene-{1·[(4-ketocyclohexyl)carbonyl]-4-hexa Hydropyridyl}-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-N- [l-(l-hexahydrop to decylacetate)-4-hexahydrop than decyl]-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[ 3,4-b]pyridine-5-carboxamide, 1-ethyl-N_{1-[(1-methyl-5-keto-3-tetrahydropyrrolyl)carbonyl]-4-hexahydropyridine }}-4·(tetrahydro-2H-piperidin-4-ylamino)-1Η·pyrazolo[3,4-7]pyridine-5-carboxamide, 1-ethyl-Ν-{1- [(3-methyl-3. epoxypropenyl)carbonyl]-4-hexahydro Pyridyl}-4-(tetrahydro-2-indole-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl·Ν-{ 1-[(4-fluorophenyl)ethenyl]_4_hexahydropyridinyl}-4-(tetrahydro-2H-pyran-4-ylamino)-1Η-ρ ratio spitting [3,4 -b]p butyl-5-cartoamine, Ν_{[1-(3,3·dimethylbutyryl)-4-hexahydrodopyl]methyl}-1-ethyl_4_ (tetrahydro-2H-bran-4-ylamino)-1Η_^ also [3,4-b]external b-position-5-carbamamine, Ν-{[1-(cyclopentylethenyl) )-4-hexahydrofolate b benzyl]methyl}-1_ethyl-4-(tetrahydro-2H-bran-4-ylamino)_1Η-ρ than ton[3,4-b] p 淀-5-carbamamine, Ν-{[1-(cyclopropylcarbonyl)-4_hexahydropyridyl]methyl}sodiumethyl-4-(tetrahydro-2H-pyran-4- Amino)-1Η-pyrazolo[3,4_b]pyridine-5-carboxamide, 87841-960303. Doc -42- 1283678 1-Ethyl-Ν-({1-[(4-fluorenylcyclohexyl)-yl]-4-ττ-chlorinated bamboo b-position}methyl)-4_(tetrahydro-2H-piperidin Isoamylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-indole-({1-[(4-phenylphenyl)acetate)- 4-hexachloro-p-predyl}methyl)-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide , 1_ethyl-Ν-({1·[(1-methyl-5·费基-3-tetrazine-exo-l-l-yl)-based]&quot;4-hexachloro-p-butyl}methyl) Ice (tetrahydro-2H-pyran-4-ylamino)-1Η-pyrazolo[3,4_b]pyridine-5-decylamine, 3-[(1-ethyl-5-{[(benzene) Methyl)amino]carbonyl]}Η·pyrazolo[3,47>p-but-4-yl)amino]cyclohexanecarboxylic acid methyl ester, 3-[(1-ethyl-5) -{[(phenylmethyl)amino]carbonyl}·1Η·pyrazolo[3,4-b]pyridin-4-yl)amino]cyclohexanecarboxylic acid, 1-ethyl-N-(benzene Methyl)-4-(4•hexahydropyridylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-4-({l-[ (Methoxy)ethinyl]-4-hexahydropyridinyl}amino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester, 1-(1·methylethyl) -4-(tetrahydro-2H-pyran Ethyl 4-aminoamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxylate, 1·ethyl-indole·(4-fluorophenyl)-6-methyl-4- (tetrahydro-2H-pyran-4-ylamino)-1Η-ρ-biazo[3,4-7]pyridine·5-formamide, 1-ethyl-6-methyl-Ν-{[ 4-(methyl-branched)phenyl]methyl}-4-(tetrahydro-2Η- shode-4-ylamino)-1Η-pyrazolo[3,4_b]pyridine-5-carboxamide , N-(2,3-Dihydro-1Η·β _2-yl)-1-ethyl-6-methyl-4-(tetrahydro-2H-hamo-4-ylamino)·1Η-ρ More than tons of [3,4_b]p than yt-5-cartoamine, 1-ethyl-N-[3-(l-hexahydropyridylcarboxy)phenyl]_4·(tetrahydro-2H- brim -4-based 87841-960303. Doc -43 - 1283678 Amino)-1Η-pyrazolo[3,4-7]pyridine-5-carboxamide, 1-ethyl-N-[4_(l-methylethyl)phenyl]·4 -(tetrahydro-2H-t-Pentan-4-ylamino)-1Η-oxazolo[3,4-7]pyridine-5-carboxamide, 1-ethyl-N-(2-fluorophenyl) )-4-(tetrahydro-2H-pyran-4-ylamino)_1H-p is more than [3,4-b]pyridine-5-carboxamide, N-{3__[(dimethylamino) Carbonyl]phenyl}sodium ethyl ice (tetrahydro-211_ shout-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, N-{4_ [(Difluoromethyl)oxy]phenyl} small ethyl ice (tetrahydro-2H-fluoren-4-ylamino)-1Η-ρ ratio and [3,4-b]p ratio _ 5_carboxylic acid amine, N_{4-[ethinyl(methyl)amino]phenyl}succinyl_4-(tetrahydro-2-oxan-4-ylamino)-1Η-ρ ratio and [ 3,4_b]p than pent-5-cartoamine, 1_ethyl-N-(4_phenyl)-4-(tetrahydro-2Η· sher-4-ylamino)_1Η-ρ ratio并和[3,4-b]p 比淀-5-甲含胺, 1_ethyl-N-[4-(4-)-based)_2_(trifluoromethyl)phenyl]_4_(four Hydrogen-2H-Bucer-4-ylamino)·1Η-ρ ratio 并[3,4-b]external b-position-5-carbamamine, 1-ethyl-N-4-p ratio -4-(tetrahydro-2H-pyran-4-ylaminol ratio Tons of [3,4-b]pyridine-5-formamide, 1-ethyl-Ν·{4·[(4-methyl-1_hexahydropyrrolidinyl)carbonyl]phenyl b-4-( Tetrahydro-2H-ipyran-4-ylamino)·1Η·external b ton[3,4_b]p ratio _5_formamidine, 1-ethyl-N_[2-(2-ketone) Small tetrahydro outside t-lyl)phenyl]_4_(tetrahydro-2H-bran-4-ylamino)·1Η-ρ than spit[3,4-b]pyridine-5-carboxamide, 1-ethyl-N-[3_(methylsulfonyl)phenyl]-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-巧匕♦[3,4-b] External b-position -5-carbamamine, N-{3_[ethyl-bromo (methyl)amino]phenyl}_1_ethyltetrahydroendanyl 87041-960303. Doc -44- 1283678 Amino)-1Η-pyrazolo[3,4-b]pyridine·5-carbamimidamine, 1-ethyl-indole-{3-[(methylsulfonyl)amino]benzene Base} ice (tetrahydro-2Η· shout-4-ylamino)-1Η-pyrazolop,4-b]pyridine-5-carboxamide, 1-ethyl-fluorene (4-fluoro group) -2_# to phenyl)-4-(tetrahydro-2H-fluoren-4-ylamino)-1Η-exo-[3,4-b]pyridin-5-carboxamide, N-( 4-Chlorophenyl)-1-ethyl·4_(tetrahydro-211_ shoutin-4_ylamino-pyrimido[3,4-b]pyridine-5-carboxamide, N-(3- Chloro-2-cyanophenyl)_1_ethyl-4-(tetrahydro-2indole-scarred-4-ylamino)-iH_ 峨 并[3,4-7]pyridine-5- formazan Amine, 1-ethyl-N-[3-(l-hexahydro-p-butyryl)-phenyl]-4-(tetrahydro-2H-pyranylamino)&quot;·1Η-ρ Ratio of [3,4-b]p to _5_甲甲胺,1_ethyl-Ν·[2-(methylsulfonate)phenyl]-4-(tetrahydro-2H-P __4_ylamino)-lH_ external oxime and [3,4-b]p than lake-5-carbamamine, N-{2_[acetoxy (methyl)amino]phenyl} small B 4-(tetrahydro-2H-fluoren-4-ylamino)_1H-p than wow[3,4-b]p than _5_cartoamine, 1-ethyl_N-[ 3-(4-moffolinyl)phenyl]-4-(tetrahydro- 2H-Brigan-4-ylamino)-1H-p is more than [3,4-b>pyramid-5.carbamamine, N-(4-chloro-3-chlorophenyl)- 1-ethyl-4-(tetrahydro-2H.pyran-4-ylamino)_1H_ outer xanthene[3,4-7]pyridine-5-carboxamide, 1-ethyl_N-(3 -light phenyl)-4-(tetrahydro-2Η- sher-4-ylamino)-1Η-ρ than gorge[3,4-b]pyridine-5-carbamamine, N_(3-chloro Phenyl)-1-ethyl-4·(tetrahydro-2H-^an-4-ylamino)-lH_leafb[3,4-b]pyridin-5-carboxamide, Ν-[ 3·[(Acetylamino)methyl]-4-(methoxy)phenyl]-l-ethyl ice (tetrahydro-2H_pipe 87841-960303. Doc -45- 1283678 -4--4-ylamino)_1H-pyrazolo[3,4-b]pyridine-5-decylamine, 1-ethyl-mole external b-precipitate 35'-branched base] -4-(tetrachloro-2H-17Guano-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, N-(3-{[cyclohexyl ( Methyl)amino]carbonyl}phenyl)-1-ethyl-4-(tetrahydro-2H-piperidin-4-ylamino)_1H-pyrazolo[3,4-b]pyridine-5_ Formamidine, 1-ethyl-N-[2-(4-indolyl)-phenyl]-4-(tetrachloro-n-butyl-4-ylamino)-1Η-外匕峻和[3 , 4-b]External b is 5--5-carbamamine, Ν-{3·[(acetamido)sulfonyl]phenyl}-1-ethyl-4·(tetrahydro-2H-pyran -4-ylamino)) Η-ρ 峻 并 [3,4-b]p than pent-5-cartoamine, N-(3-chloro-4-phenyl)-1-ethyl- 4-(tetrahydro-2H-fluoren-4-ylamino)-1Η-ylidene[3,4-b]pyridine-5-carboxamide, 1-ethyl-N-{4-[ (Methanesulfonyl)amino]phenyl}-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide , 1-ethyl-indole-{3·[(methylamino)-based]phenyl}_4-(tetrahydro-2H-pyro- 4-ylamino)_1Η-pyrazolo[3,4- b]pyridine·5·carbamamine, 1-ethyl-4-(tetrahydro-2Η-bran-4-ylamino group )·Ν-[3-(trifluoromethyl)phenyl]-1Η-exopurin and [3,4-b>pyridin-5-formamide, 1-ethyl-N-3-external b Precipitate-4-(tetrahydro-2H-pyran-4-ylamino)-1H-p is more than [3,4-b>pyramid-5-carbamide, N-(3,4- Diphenylphenyl)-1-ethyl-4·(tetrahydro-2H-pyran-4-ylamino)-1Η-ρ ratio [3,4-7]pyridine-5-carboxamide, N -[3-(Amino aryl)-4-chlorophenyl]succinyl_4_(tetrahydro-2H-bran-4-ylamino)-1H-external T and P,4-b&gt ; 比盐-5_Metaguanamine, 1-ethyl-N-[3-(4-norfosinyl)phenyl]-4_(tetrahydro-2H&gt;endan-4-ylamino)-1Η · 87841-960303. Doc -46- 1283678 匕 匕 并 [3,4-b] 峨 -5 -5 - carboxylic acid amine, 1-ethyl-N-[4-(4- 福 p 林 林 ) )) phenyl]- 4-(tetrahydro-2H-isanyl-furylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carbamamine, 1·ethyl-N-{2_[(4- Mercapto-1-7T 卩 卩 p ) ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] Pyridine-5-formamide, N-{2-[(dimethylamino)carbonyl]phenyl}-1·ethyl-4·(tetrahydro-2H_^an-4-ylamino)-1Η -pyrazolo[3,4-b]pyridine-5-carboxamide, N-[2-chloro-4-(trifluoromethyl)phenyl]succinyl_4_(tetrahydro-2H-britt __4_ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, N-{2_[(acetic acid amino)methyl]phenyl}-1-ethyl 4-(tetrahydro-2Η-^anylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, N-(2-chlorophenyl)succinyl-4 -(tetranitro-2H-pyran-4-ylaminolpyrazine[3,4_b]pyridin-5-carboxamide, N-(3-chloro-2-fluorophenyl)-1•ethyl -4-(tetrahydro-2H. sulphonyl-4-ylamino)·ιη_ρbiazo[3,4-7]pyridin-5-carboxamide, 1-ethyl-indole-(3-fluorophenyl) )-4-(tetraindole-2Η-jol-4-ylamine )-1Η_ρ比比和[3,4-b]pyridine-5-carboxamide, N-(2-cyano-3-phenylphenyl)_1_ethyl-4-(tetrahydro-2H_ shout -4-ylamino)-1Η-ρ-pyrazolo[3,4-pyridin-5-carboxamide, 1-ethyl-indole-[4-(propyl aryl)phenyl]-4 -(tetrachloro-2Η.. ρ南-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine·5-formamide, Ν-{4-[(dimethylamino) )carbonyl]phenyl}-1·ethyl-4-(tetrahydro-2-indole-ytyl-4-ylamino)-lHw than ton[3,4_b> butyl _5-formic acid amine, 1-B --N-[4-(methyl fluorenyl) phenyl] ice (tetrahydro-2H_^ -4-ylamino)-1Η- 87841-960303. Doc -47- 1283678 峨 并 [3,4 七] 外 b丁-5-carbamamine, N-{4-[(acetic acid amino)methyl]-meryl}-1-ethyl-4-( Tetrachloro-2H-pyran-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, N-({2_[(1,1-dimethyl) ))oxy]_3-ρ ratio decyl}methyl)-1-ethyl-4_(tetrahydro-211-anthracene-4-ylamino)-1Η·pyridin[3,4-b] Pyridinium_5_carbamamine trifluorocurate, Ν-[(3·chloro-4-methylphenyl)methyl]sodiumethylidene (tetrahydro-2H-pyran-4-ylamine Base)·1Η_ρ比峻和[3,4-b&gt; 比丁-5-carbamamine, N-[(4-chloro-2-methylphenyl)methyl]succinyl_4-(four Hydrogen-2H-furan-4-ylamino)·1Η-ρ is more than [3,4-b]p than pent-5-ylamine, Ν·({2_[(monomethyl))) Benki}methyl)-1-ethyl-4_(tetrachloro-211*^ 喃 _4_ ylamino)-1Η-ρ ratio ton [3,4 VII] ratio &lt;-5-Proline, 1-ethyl-indole_({2_[(1-methylethyl)oxy)phenyl}methyl)_4_(tetrahydroanthracene-pyranyl-4) Base)-1Η-ρ ratio and [3,4-b]p ratio _5_甲甲胺, 1-ethyl-Ν·({3·[(1·methylethyl)oxy)benzene }) methyl) ice (tetrahydro-2H-pyran-4-ylamino)·1Η-ρ than 唆[3,4-b]p than _5_甲甲胺, N-({3 -[(difluoromethyl)oxy]phenyl}methyl)·1·ethyl winter (tetrahydro-2H n-yl 4-ylamino)-1Η-ρ ratio [3,4-b&gt;比丁-5_甲甲胺, 1-ethyl-Ν_{[4-#methyl-3-(methoxy)phenyl]methyl}_4-(tetrahydro-2-indole-bran-4-ylamine -1 Η-pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(5-ethinyl-2-hydroxyphenyl)methyl]succinyl 4- 4- Hydrogen-2H-pyranyl-4-ylamino)·1Η-ρ ratio Jun [3,4-b> butyl--5-carbamamine, 1-ethyl-4-(tetrahydro-2H- shouting喃-4-ylamino)·Ν-{2_[3_(trifluoromethyl)benzene its]ethyl}-1Η_ρ 比吨[3,4-b> butyl--5-carbamamine, 87841- 960303.doc -48- 1283678 N-{[4-(Acetylamino)phenyl]methyl}sodiumethyl_4_(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazole And [3,4-b]pyridine-5-A Indoleamine, 1-ethyl-N-[2-(3-hydroxyphenyl)ethyl]-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3, 4-b]pyridine_5_formamide, 1^-[2-(3_murine)ethyl]_1-ethyl-4-(tetrazalida-4-ylamino)-1Η- ρ 比 并[3,4-b]pyridine-5-carboxamide, 1-ethyl-4-(tetrahydro-2H-piperidin-4-ylamino)-N-(2-{4- [(Trifluoromethyl)oxy]phenyl}ethyl HH-pyrazolo[3,4-b]pyridine-5.carboxamide, 1_ethyl·Ν-{2-[3_(methoxy Phenyl]ethyl}-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-ρ is more than [3,4-b> than biting _5_formamide, Ν -[2·(4-Ethylphenyl)ethyl]-1-ethyl-4-(tetrachloro-2Η-ρ-decyl-4-ylamino)-1Η-pyrazolo[3,4 -b]pyridine-5-carboxamide, N-[2-(3,4-dichlorophenyl)ethyl]-1-ethyl-4.(tetrahydro-2H-pyran-4-ylamine -1Η-pyrazolo[3,4_b]pyridine-5-carboxamide, N-{2-[3-(aminosulfonyl)phenyl]ethyl}ethylethyl-4-(four Hydrogen 2H-pyran-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carbamimidamine, N-{2-[3,4-bis(decyloxy) Phenyl]ethyl}sodiumethyl_4-(tetrahydro-211-piperidin-4-ylamino)-1Η·pyrazolo[3,4-b]pyridine-5- Indoleamine, N-[2-2,3-dichlorophenyl)ethyl]-1-ethyl-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[ 3,4_b]pyridine-5-formamide, N-{2-[3,5-bis(methoxy)phenyl]ethyl}sodiumethyl 4-(tetrahydro-2H-pyran-4 -ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-formamide, 1-ethyl-N-{2-[3-methyl-4-(methoxy)benzene Ethyl]ethyl}-4-(tetrahydro-2H-piperidin-4-ylamino)_1H-pyrazolo[3,4-b]pyridine-5-carboxamide, 87841-960303.doc -49 - 1283678 N-[2_(2,6-Difluorophenyl)ethyl]-1_ethyl-4-(tetrahydro-2H-bromo-4-ylamino)-1H-p ratio olfactory [ 3,4-b deductive pentane-5-cartoamine, N_{2-[2,6-bis(methoxy)phenyl]ethyl}_1_ethyl_4_(tetrahydro-2H4-an-4 -ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-N-[2-(2-methylphenyl)ethyl]-4- (tetrahydro-2H_ shout-4-ylamino)-1Η- 匕 匕 并 [3,4-b]p than lake 5-carbamide, N-[(3,4-dimethyl) Phenyl)methyl]-1-ethyl-4-(tetrahydro-2H-bromo- 4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carbamimidamine, N-[4,5-bis(methoxy)-2,3-dihydro-1H-indol-2-yl H-ethyl_4-(tetrahydro-211_ shouting- 4-Aminoamino)-1Η-external b ox[3,4-b]external b-position-5-formic acid amine, Ν-{2·[4-(amino sulfhydryl)phenyl]ethyl} 1-ethyl-4-(tetrahydro-2H-bromo-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carbamimid, 1-ethyl-N -{[2-(methyl succinyl)phenyl]methyl}·4-(tetrahydro-2H-bran-4-ylamino)·1Η-pyrazolo[3,4_b]pyridine_ 5_Mercaptoamine, 1_ethyl-N-(2-phenylethyl)-4-(tetrachloro-2H-bran-4-ylamino)-1Η-ρ is 唆[3,4 -b]pyridine-5-carboxamide, Ν·{[4-(dimethylamino)phenyl]methyl}sodiumethyl-4-(tetrahydro-2H-pyran-4-ylamino) -1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-indole-[2-(4-fluorophenyl)ethyl]-4-(tetrahydro-2H-piperidin __4_ylamino)·1Η_pyrido[3,4-b]p than lake-5-formamide, 1-ethyl-Ν·[2-(4-methylphenyl) Base]-4-(tetrahydro-2H-^an-4-ylamino)-1Η-p ratio spit [3,4-7] than _5_甲甲胺, N_{[3-(amino group Sulfhydryl)phenyl]methyl}sodiumethyl 4-(tetrahydro-211-piperidinylamino)-1Η_ρ比比[3,4-b]p than lake-5-cartoamine , 87841-960303.doc -50· 1283678 1-ethyl_N-[(4-methylphenyl) Methyl]-4-(tetrahydro-2H.pyran-4-ylamino)-1Η-is eaten [3,4-b]pyridine-5-carboxamide, 1·ethyl-N_{[ 4-Denyl-3-(trimethylmethyl)phenyl]indolyl}-4-(tetrahydroendan-4-ylamino)·1Η·pyrazolo[3,4-b]pyridine-5- Formamidine, 2-[({[1_ethyl-4·(tetrahydro-2H- 喊 __4_ylamino) is more than [3,4-b]p than pent-5-yl] N-[(6-murine-2-pyranyl)methyl]-1-ethyl-4_(tetrachlorohexan-4-ylamine) Base)-1Η·pyrazolo[3,4-b]pyridine-5-carbamidamine trifluoroacetate, N-(2,3-dichloro-1H-buri-1 base)_1_ethyl- 4-(tetrachloro-2H·^-endan-4-ylamino)_1H_ outer 1: bite [3,4-b]pyridine-5-carboxamide, N_({2-[ethyl fluorenyl (A) Amino]phenyl}methyl)methylethyl-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5- Indoleamine, N-[(lS)-2,3-dichloro-111_in-1-yl]-1-ethyl-4-(tetrachloro-2H-pyran-4-ylamino)-1Η -ρ ratio is also [3,4_b] 匕 匕 -5 - 酿 胺, N-[(lR)-2,3-dihydro-1H·茚-1-yl] small ethyl-4·(four Hydrogen-2H-piperazin-4-ylamino)-1Η·pyrazolo®; 3,4-b]pyridine_5-carbamamine, 1- -N-({3-[(methylsulfonyl)amino]phenyl}methyl)-4-(tetrahydro-2H-piperidin-4-ylamino)_1H-pyrazolo[3, 4-b]pyridine-5_carbamamine, 1_ethyl·N-(l-phenyl_4_hexahydropyridyl)-4-(tetrahydro-2H-piperidin-4ylamino) -1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-N-{1_[(ethylamino)carbonyl]-4-hexahydropyridyl}-4-( Tetrahydro-2H-piperazin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5·carboxamide, formic acid small ethyl-N-[l-methyl-2- (4-mercapto-1-hexahydropyridinyl)ethyl]4-(tetrahydro-2H-pyran-4-ylamino)-1Η-pyrazolop,4-b]pyridine_5· Methionamine (1: 1), 87841-960303.doc -51- 1283678 [4-({[l-ethyl-4-(tetrahydro-2H·bromo-4-ylamino)-1Η_ρ) And [3,4-b]p is more than 5-amino]carbonyl}amino)-1-hexahydropyridinyl]acetate, 1-ethyl-N-{[4-(4-? Methyl)phenyl]methyl}_4-(tetrahydro-2H-bran-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carbenamide trifluoroacetic acid Salt, 1-ethyl-N_({3-[(4-methyl hexahydropyranyl)methyl]phenyl}methyl)-4·(tetrahydro-2H· sher-4-ylamine) Base)-1H-p ratio and [3,4-b&gt; 5_ formic acid amine trifluoroacetic acid ητΛ£ salt, Ν-{[5-(amine-based)-3-p ratio benzyl]methyl}-1-ethyl-4_(tetrachloro-2Η-0 -4_ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carbamimid trifluoroacetate, 1-ethyl-N_{[4-(1-methylethyl)benzene Methyl}_4-(tetrahydro-2H-pyran-4-ylamino)_1H-pyrazolo[3,4-b]pyridine-5-carboxamide, N-{[3-(ring Pentyloxy)-4-(methoxy)phenyl]methyl}sodiumethyl-4-(tetrahydro-2H-piperidinylamino)_1H_pyrazolo[3,4-b]pyridine- 5. Myramine, 1_ethyl-Ν·({4-[(4-methyl hexahydropyranyl)methyl]phenyl}methyl) ice (tetrahydro-2Η-slightly-4 -ylamino)-1Η-ρ ratio and [3,4-b]p than pent-5-caraamine trifluoroacetate, N-[(2,4-dichlorophenyl)methyl]- 1-ethyl-4-(tetrahydro-2H-piperazin-4-ylamino)_1H-pyrazolo[3,4-b]pyridine-5.carboxamide, Ν·[(2,4- Difluorophenyl)methyl]sodiumethyl-4-(tetrahydro-2Η-piperidin-4-ylamino)_1Η·pyrido[3,4-b]pyridine-5-carboxamide, N -[(2-Alkyl-4-fluorophenyl)methyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1Η·pyrine[3,4 -b]pyridine-5-carbamamine, N-{2- [2-lacyl-3-(methoxy)phenyl]ethyl}-1-ethyl-4-(tetraqi-2H_ shouting _4_ylamino)-1Η-pyrazolo[3, 4-b]pyridine-5-carboxamide, 87841-960303.doc -52- 1283678 3-[({[1-ethyl ice(tetrahydro-2H-piperidin-4-ylamino)-1Η- Methyl pyrazolo[3,4-b]pyridin-5-yl]carbonyl}amino)methyl]benzoate, 1-ethyl-indole-{[3-(1-tetrahydro-p-l-l-yl) Phenyl]methyl}-4-(tetrahydro-2H-(anthyl-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide trifluoroacetate , 1-ethyl-N-(2-{4-[(sudecanoyl)amino]phenyl}ethyl)-4-(tetrahydro-2H-pyran-4-ylamino)-1Η ·ρ ratio spit [3,4_b]p than lake-5-cartoamine, N-{[2,5-bis(methoxy)phenyl]methyl}-1-ethyl-4-(four Nitrogen-2H-yt-4-ylamino)-1Η-external b-[3,4-b]p than pent-5-cartoamine, N-{[2,6-bis(methoxy) Phenyl]methyl}_1_ethyl-4_(tetrahydro-2H-bran-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 1 -ethyl·Ν-[(2-fluorophenyl)methyl]-4·(tetrahydro-2H· 喃 __4_ylamino)-1Η-exocarbazo[3,4-b]pyridine -5-Mergamine, N-[(3,5-difluorophenyl)methyl]-1-ethyl- 4-(tetrahydro-2Hh-Pentan-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, N_[(4-chlorophenyl)methyl]-1 -ethyl-4-(tetrahydro-2-indolyl-oxan-4-ylamino)-1Η-峨君[3,4-b]external 1:precipitate-5-formamide, N-cyclohexyl_ 1-ethyl-4-(tetramethylene-2H-piperan-4-ylamino)&gt;1H-pyrazolo[3,4_b] 竹匕盐-5-甲含胺, 1-ethyl·Ν_{ 2·[4-(A)-phenyl]ethyl}-4-(tetrahydro-2H_pyran-4-ylamino)-1Η·pyrazolo[3,4-b]pyridine- 5_Mercaptoamine, 1_ethyl-Ν_{[2-fluoro-3-(trifluoromethyl)phenyl]methyl b 4_(tetrahydrojH-pyran-4-ylamino)-1Η -ρ is more than [3,4-b]p than bite-5-cartoamine, N_({4-[(cyclopropylamino)carbonyl]phenyl}methyl)_1_ethyl_4_(tetrahydrogen)喃冰基基基比比和[3,4-b]p 比淀-5-甲含胺, 87841-960303.doc -53 - 1283678 1-ethyl-N-{[4-(4-methyl _1·Hexahydropyrrole)Phenyl]methyl b 4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-A Indoleamine, 1-ethyl-N_{[4-(1•tetrahydropyrrolylmethyl)phenyl]methyl b 4-(tetrahydro-2H-pyran-4-ylamino)·1Η·pyridyl Zoxa[3,4_b]pyridine-5-A Indoleamine, 1_ethyl-N-[6-(methoxy)-1-keto-2,3-dihydro_1Η·indol-2-yl]·4-(tetrahydro-2H-pyran- 4-ylamino)·1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(2,5_ &lt;One milk base) methyl]-1-ethyl-4-(tetramethane-4-ylamino)_1H_pyrazolo[3,4-b]pyridine-5-carboxamide, N -[(3,5-diethylphenyl)methyl]_1_ethyl_4_(tetrahydro-2H-piperazin-4-ylamino) is more than [3,4-b] 5-carbamimidamine, N-[(2,3-mono-methacrylic)methyl]_1_ethyl-4·(tetrachloro-2H-bungan-4-ylamino)-1Η_pyrazolo[3 , 4_b]pyridine-5-carbamamine, 1-ethyl_N-{[2_(methylsulfonyl)phenyl]methyl}-4·(tetrahydro-2H-piperazin-4-ylamino )_1H_pyrazolo[3,4-b]pyridine-5-formamide, 1-ethyl_N_[(3-hydroxyphenyl)methyl]-4·(tetrahydro-2H-pyran) 4-ylamino)-1Η-pyrazolo[3,4_b]pyridine-5-carboxamide, N-{[3,5-bis(methoxy)phenyl]methyl bromide ethyl winter ( Tetrahydro-2H_pyran-4-ylamino HH-pyrazolo[3,4-b]pyrazine-5-carboxamide, 1-ethyl-N-[2_(4_phenyl) Ethyl]-4-(tetrahydro-2H-fluorenyl-4-ylamino)-1Η-pyridin[3,4-b]ii than pent-5-cartoamine, N-[(3, 5-monophenyl)methyl]sodiumethyl-4-(tetrahydro-2indole-scarred-4-ylamino)-1Η_pyrazolo[3,4_b]pyridine-5-carboxamide, N-{ [2,4-bis(methoxy)phenyl]methyl b _4·(tetrahydro-2Η_scarredanylamino)_1Η-pyrido[3,4-b]pyridine-5-carboxamide, 87841.960303.doc -54- 1283678 1-ethyl-N-{[ 2-(Methoxy)phenyl]methyl}-4-(tetrahydro-2H-pyran-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-formamidine Amine, N-[(2,4-dimethylphenyl)methyl]sodiumethyl-4-(tetrahydro-2H-piperidinylamino)-1Η-pyrazolo[3,4-b Pyridine-5-formamide, 1-ethyl-fluorenyl ({2-[(methylamino)carbonyl)phenyl}methyl)-4_(tetrahydro-2H-pyran-4-ylamino) -1Η·pyrazolo[3,4-b]pyridine-5-formamide, 1-ethyl-N-{2-[4-(methoxy)phenyl]ethyl}-4-( Tetrahydro-2Η-scaridin-4-ylamino)-1Η^ is more than [3,4-b>pyramid-5-formamide, N-[(2-chlorophenyl)methyl] -1_ethyl-4-(tetrahydro-2H-fluoren-4-ylamino group ratio and [3,4-b]p ratio bite-5-formic acid amine' 1-ethyl-N-[( 2_# is phenyl)methyl]-4-(tetrahydro-2H- sher-4-ylamino)·1Η-external b and [3,4-b> butyl--5-carbamamine, N-(l,3-benzodioxolan-4-ylmethyl)-1-ethyl-4·(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazole [3,4-b]pyridine-5-formamide, 1-ethyl·Ν-[3-( Oxy)phenyl]-4-(tetrahydro-2-indolyl-4-ylamino)-1Η-pyrido[3,4-b]p than pent-5-cartoamine, N-( Cyclohexylmethyl)sodiumethyl-4-(tetrahydro-2H_ycyl-4-ylamino)-1H-p is more than [3,4-b]pyridine-5-carboxamide, 1- Ethyl·Ν·(1,2,3,4·tetrahydro-1_fluorenyl)_4-(tetrahydro-2H-piperidinylamino)-1Η-p ratio spitting [3,4-b ]p-precipitate-5-formic acid amine, 4_[({|&gt;ethyl-4·(tetrahydro-211-hamo-4-ylamino)-1Η-pyrazolo[3,4-b] Bamboo b-pyridyl]carbonyl}amino)methyl]benzoic acid methyl ester, Ν-[(3,4·dichlorophenyl)methyl]sodiumethyl 4-(tetrahydro-2H-pyran-4 -ylamino)-1Η-pyrazolo[3,4-b>pyridin-5-formamide 87841-960303.doc -55- 1283678 N-{[4-(aminocarbonyl)phenyl]- -1-}-1-ethyl-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide N-[(2 ,6-difluorophenyl)methyl]-1_ethyl-4-(tetrahydro-2H-furan-4-ylamino)_iH_pyrazolo[3,4-b]pyridine-5-A Indoleamine N-{[3-(amino)phenyl]methyl}methylethyl-4-(tetrahydro-2-H-pyran-4-ylamino)-1Η·pyrazolo[3, 4-b]pyridine·5·carbamidine 1-ethyl-hydrazine-[(4-per benzene) Methyl]-4-(tetrahydro-2Η-*7 guolate-4-ylamino)-1Η-ρ-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-B --N-{[6-(methoxy)-3-exo b-butyl]methyl}-4-(tetrahydro-2H-bran-4-ylamino)-1Η-pyrazolo[3 , 4-b]pyridine-5-formamide 1-ethyl than decylmethyl)-4-(tetrachloro-2H-P-decano-4-ylamino)-1Η-ρ ratio spit[3 ,4-b]pyridine-5-carbamimidamine 1-ethyl-4-(tetrahydro-2H-piperidin-4-ylamino)·Ν-{[3_(trifluoromethyl)phenyl]- }}-1Η-pyrido[3,4-b]pyridine-5-carbamimidoxime [4-(2-amino-2-ketoethyl)phenyl]pyridin-4-( Tetrahydro-2H-piperazin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine_5-carbamimidamine 1-ethyl-oxime ({4-[(methylamino) )carbonyl]phenyl}methyl)-4-(tetrahydro-2H-piperidin-4-ylamino)_1H-pyrazolo[3,4-b]pyridine_5-carbamimidamine 1-ethyl -Ν·{4-[2-(Methylamino)-2. ketoethyl]phenyl} Winter (tetrahydro-2H-piperazin-4-ylamino HH-pyrazolo[3,4- b] Pyridin-5-formamide 1-ethyl-N-[(3-fluorophenyl)methyl]-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazole [3,4-b]pyridine-5-carbamamine 1_ethyl_N-({4-[(methylsulfonyl)amino]phenyl} Base)_4_(tetrahydro-2H-piperidinylamino)-1Η-pyrazolo[3,4-b]pyridine-5-formamide 87841-960303.doc -56- 1283678 N-{[4 -(Amino sulphonyl)phenyl]methyl}-l-ethyl-4·(tetramethane-4-ylamino)·1Η-pyrazolo[3,4_b]pyridine_5_A Indoleamine N-{[2-(aminowei)phenyl]methyl}_1_ethyl-4-(tetrachloro-2-indolyl-4-ylamino)-1Η-pyrazolo[3, 4-b]pyridine-5-carboxamide N-({4-[(difluoromethyl)oxy)phenyl}methyl)_1_ethyl·4-(tetrahydropyran-4-ylamine) Base)·1Η_pyrazolo[3,4-7]pyridine-5-carbamimidoxime-({3-[(dimethylamino)methyl]phenyl}methyl)-1•ethyl-4 -(tetrahydro-2-indole-pyranylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide N-{[3-chloro-4-(methoxy) Phenyl]methyl}sodiumethyl-4-(tetrachloro-2H-methane-4-ylamino)-1Η-pyrazolop,4-b]pyridine-5-carbamimidoxime-(1 ·Ethyl-based 4-TT nitrogen ρ than decyl ethyl-4-(tetraqi-211·^-decano-4-ylamino)-1Η-ρ ratio and p,4-b] 5-carboxamide 1-ethyl-4-(tetrahydro-2H-bran-4-ylamino)-N-{[2-(trifluoromethyl)phenyl]methyl}·1Η-pyridyl Zoxa[3,4_b]pyridine-5-carboxamide N_(5·Chloro-2,3-dihydro-1H-hetero-2·yl)-1•ethyl-4-(tetraqi_2Η_ι派喃_4_ylamino)-1Η-pyrazole [3,4-b]pyridine-5-formamide N-({3-[(ethylamino)methyl]phenyl}methyl)·1_ethyl_4-(tetrahydro·2Η&gt; Decano-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 1-ethyl·Ν-[(4-fluorophenyl)methyl]-4- (tetrahydro-2H-pyran-4-ylamino)-1Η-pyrazolo[3,4_b]pyridine-5-carboxamide 1-ethyl-indole-{[4-|^yl-2- (trifluoromethyl)phenyl]methyl}_4_(tetrahydro-2H_ shout-4-ylamino)_1Η-ρ than spit [3,4-b]externate b-5-carboxylic acid amine 1 Ethyl-N-[(2-ethylphenyl)methyl]-4-(tetrahydro-2H-pyran-4-ylamino)-1Η-竹1: oxazo[3,4-b Pyridine-5-formamide 87041-960303.doc -57- 1283678 1-ethyl-N-{[2-fluoro-5-(trifluoromethyl)phenyl]methyl}-4-(four Hydrogen-2H--pyran-4-ylamino group is more than bite [3,4-b]p than bite-5-formic acid amine 1-ethyl-4_(tetrahydro-2H_pyranyl-4-ylamino) )-N-[(2,3,4-trifluorophenyl)methyl]-1Η-ρ ratio also [3,4-b]p than pent-5-cartoamine N-[(4-chloro Base 2_fluorophenyl)methyl]-1·ethyl-4-(tetrahydro-2H- sher-4-ylamino group is more than [3,4-b] ?比盐-5-Medralamine N-[(4-bromo-2-fluorophenyl)methyl]-1-ethyl-4-(tetrahydro-2H-pyran-4-ylamino) -1Η-pyrido[3,4-b]pyridine-5-formamide N-[(3,5-dimethylphenyl)methyl]-1-ethyl-4-(tetrahydro-2H -Nam-4-ylamino)-1Η-pyrazolo[3,4_b]pyridine-5-carboxamide N-[(2,3-dimethylphenyl)methyl]-1-ethyl -4-(tetrahydro-2H-pyran-4-ylamino)-1Η-pyrido[3,4-b]pyridine-5-carboxamide N-[(2,3-diphenyl) )methyl]-1-ethyl·4-(tetrahydro-2-indole-indole-4-ylamino)-1Η-pyrazolo[3,4_b]pyridine-5-carboxamide N-[( 4-cyanophenyl)methyl]_1·ethyl-4-(tetrahydro-2H-jum- 4-ylamino)-1Η-external 并[[,4-b] 外 1 : -5-formic acid amine N-[(4-bromophenyl)methyl]-1-ethyl-4-(tetrahydro-2H-fluorenyl-4-ylamino)-lH-mouth-pyrazole[3 ,4-b]pyridine-5-carboxamide 1-ethyl-N-{[5-fluoro-2-((trifluoromethyl)phenyl]methyl b 4-(tetrahydro-2H- shouting- 4-Aminoamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 1-ethyl-N-[(4-phenylphenyl)methyl]·4-(tetrahydrogen) -2H_ shout-4-ylamino)-1Η_f-oxazolo[3,4-b]pyridine-5-carbamimidoxime-{[4-(1,1-dimethylethyl) Phenyl]methyl}sodiumethyl-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 87841- 960303.doc -58 - 1283678 N_[(3-Phenylphenyl)methyl]-1-ethyl-4-(tetrahydro-2H-fluoren-4-ylamino)-1Η-p is 唆[3,4-b]p bis--5-cartoamine N-[(2,6-dichlorophenyl)methyl]sodiumethyl 4-(tetrahydro-2-vanopan-4-yl Amino)-1Η-oxazolo[3,4-b]pyridine-5-formamide N-[(5-chloro-2-methylphenyl)methyl]-1_ethyl-4- (tetrahydro-2H-pyran-4)-amino-aminopyrazine[3,4-b]pyridinium-5-carbamimidamine N-[(3,5-dibromophenyl)methyl; _Mercapto-4-(tetrahydro-2H-pyran-4-ylamino)-1Η_pyrazolo[3,4-b]pyridine-5-carboxamide 1_ethyl·Ν-[(4 _Ethylphenyl)methyl]-4-(tetrahydro-2H-fluorenyl-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide 1-B -N-{[3_Fluoro-4-(trifluoromethyl)phenyl]methyl}-4-(tetrahydro-2H-pyran-4-ylamino)-1Η-pyrazolo[ 3,4-b]pyridine-5-carboxamide 1-ethyl-N-[(2-molyl)methyl]-4-(tetrahydro-2H-^an-4-ylamino)_1H- P-pyrazolo[3,4-7]pyridine-5-carboxamide N-[(2-bromophenyl)methyl]-1_ethyl-4 ·(tetrahydro-2H&gt; chen _4·ylamino)-iH_external oxime also [3,4-b> butyl--5-carbamamine 1-ethyl-Ν-{[4·( Methyl)phenyl]methyl}-4-(tetrahydro-2H-fluorenylamino)-1Η-pyrido[3,4-b]p than bite-5-carboxamide-1 Ethyl-N-{[3-(hydroxymethyl)phenyl]methyl}_4-(tetrahydro-2H_pyran-4-ylamino)-1Η-pyrido[3,4-b] Pyridine-5-carbamimidamine 1-ethyl-N-{[3-(hydroxymethyl)-2-methylphenyl]methyl b 4-(tetrahydro-2H_p-exan-4-ylamino) -1Η-pyrazolo[3,4-b]pyridine_5_carbamimidamine N-{[2&gt;dichloro-6-(methyl)phenyl]methyl}small ethyl benzene (tetrahydro-2)迅 喃 喃 ) ) Η Η Η Η Η Η 吡 吡 878 878 878 878 878 878 878 878 878 878 878 878 878 878 878 878 878 878 878 878 878 878 878 878 878 878 878 878 878 878 878 878 878 878 878 878 878 878 Methylphenyl)methyl]-1-ethyl-4-(tetrahydro-2H&gt; oxa-4-ylamino)-1Η-ρ is more than [3,4-b] external b bit-5 _ formic acid amine 1-ethyl-N-{[4-(2-methylpropyl)phenyl]methyl}-4·(tetrahydro-2Η·piperan-4-ylamino)-1Η-ρ唆和[3,4_b&gt; 比淀-5_甲甲胺N-[(2,5-Dimethylphenyl)methyl]-1-ethyl-4-(tetrahydro-2H- shouting - 4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5-methanamine 1-B 4-(tetrahydro-2H-bromo-4-ylamino)-N-[(2,4,5-trifluorophenyl)methyl]-1Η-pyrazolo[3,4-b Pyridine-5-formamide 1-ethyl-N-{[2-fluoro-4-(trifluoromethyl)phenyl]methyl}-4-(tetrahydro-2H-pyran-4- Amino group)-1Η_ρ ratio Jun [3,4-b]p ratio attack-5-formic acid amine N-[(2-chloro-6-methylphenyl)methyl]-1-ethyl-4 -(tetrahydro-2H&gt; decyl-4-ylamino)·1Η-β ratio also [3,4-b]p than dian-5-anthracene 4_[({[1_ethyl·4 · (tetrahydro-2H-pyran-4-ylamino)-1Η-pyrazolo[3,4-b]pyridin-5-yl]carbonyl}amino)methyl]benzoic acid sodium salt 3-[( {[1-ethyl-4-(tetrahydro-2H-piperazin-4-ylamino)-1Η-pyrazoloindole, 4-7]pyridin-5-yl]carbonyl}amino)methyl]benzene 1-ethyl-4-{[4-(hydroxyimino)cyclohexyl]amino}_1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester 1-ethyl-4_ {[4-(Hydroxyimino)cyclohexyl]amino}-N-{[4_(methoxy)phenyl]methyl}-1Η_ρ is 岐[3,4-b]p than 淀-5 -cartosamine N-{[4-(dimethylamino)phenyl]methyl}methylethyl-4-{[4-(hydroxyimino)cyclohexyl]amino}-1Η-pyrazole [3,4-b]pyridine-5-carboxamide 1_ethyl-4-({4-[(ethoxy) Imino]cyclohexyl}amino)-N-{[4-(methoxy)phenyl]methyl b 1H-pyrazolo[3,4-7]pyridine-5-carboxamide 87841-960303. Doc -60- 1283678 1_Ethyl_4-({4-[(methoxy)imino]cyclohexyl}amino)-indole-{[4·(methoxy)phenyl]methyl HH -pyrazolo[3,4-b]pyridine-5-carboxamide 4_[(4-{[(1,1-dimethylethyl)oxy]imino]cyclohexyl)amino]- 1-ethyl-N_{[4-(decyloxy)phenyl]methyl}_ih-pyrazolo[3,4-b]pyridine-5-carboxamide 1_ethyl_N-{[4_ (Methoxy)phenyl]methyl}-4-[(7-ketohexahydro-1H--azadecen-4-yl)amino]_1H_pyrazolop,4_b]pyridine-5 -Procarbamide 1-ethyl-4-[(7-ketohexahydro-1H--azepten-4-yl)amino]-1H-pyrazolo[3,4-b]pyridine- 5-carboxylic acid ethyl ester 4-{[cis-4-(butylamino)cyclohexyl]aminobine N-(2,3-dihydro-1H-indol-2-yl)_1_ethyl- lH-p ratio spit [3,4-b] bamboo b-precipitate-5-formic acid amine 4·[(trans-amylcyclohexyl)amino]ethyl-N-(phenylmethyl)-1Η -pyrazolo[3,4-b]pyridine-5-carbamimid-4-[(trans-2-aminocyclohexyl)amino)1-1-ethyl(phenylmethyl)-1Η-pyridyl Zoxa[3,4-b]pyridine-5- Indole 4-[(cis-2-aminocyclohexyl)amino]-1-ethyl-N-(phenylmethyl)-1Η-pyrazolo[3,4-b]pyridine-5- Formamide, 4-[(3-aminocyclohexyl)amino H-ethyl-N-(phenylmethyl)_1H-pyrazolo[3,4-7]pyridine-5-carboxamide, 1 -ethyl-4{[(lSR,3RS)-3-ylcyclohexyl]amine-based ox[3,4-b]p-pyridyl-5-carboxylic acid ethyl ester, N,l-diethyl -4-{[(lSR,3RS)-3-ylcyclohexyl]amino group iH-ρ than spit [3,4-b]pyridine-5-carboxamide, 1_ethyl-Ν·( 4-fluorophenyl)-4_{[(lSR,3RS)-3_# is based on cyclohexyl]amino group ih_ borazo[3,4-7]pyridine-5-carboxamide, 87841-960303. Doc -61 - 1283678 1-Ethyl-4-{[(lSR,3RS)_3-hydroxycyclohexyl]amino}-Ν·(1,3-pyrazole-2-ylmethyl)-1Η-pyrazole And [3,4-b]pyridine-5-formamide, 1-ethyl-N-[(4-fluorophenyl)methyl]-4-{[(lSR,3RS)-3-hydroxycyclohexyl Amino}-1Η-leaf b and P,4-b]exo I: ammonium-5-formic acid amine, 1-ethyl_4_{[(lSR,3RS)-3-hydroxycyclohexyl]amino} -N-{[4_(methylsulfonyl)phenyl]methyl b 1H-pyrazolo[3,4_b]pyridine-5-carboxamide, N-{[3,4-bis(methoxy) Phenyl]methyl} Small ethyl-4-{[(lSR,3RS)-3-hydroxycyclohexyl]amino}_1H-pyrazolo[3,4_b]pyridine-5-carboxamide, 1-ethyl-4-{[ (lSR,3RS)_3-hydroxycyclohexyl]aminopyridyl N-(2-pyridylmethyl)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl- 4-{[(lSR,3RS)-3-hydroxycyclohexyl]amino}-indole-[(1-methyl-1H-pyrazol-4-yl)methyl]-1H·pyrazolo[3, 4-b]pyridine-5-carboxamide, N-[(3,4-dimethylphenyl)methyl]-1-ethyl-4_{[(1SR,3RS)_3-hydroxycyclohexyl]amine }}-1Η·pyrazolo[3,4-b]pyridine-5-carboxamide, 1_ethyl-4-{[(lSR,3RS)-3-hydroxycyclohexyl]amine b-N-{ [4-(Methoxy)phenyl]methyl}-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(2,4-didecylphenyl) A Small ethyl-4-{[(lSR,3RS)-3-hydroxycyclohexyl]amino}-1Η·pyrazolo[3,4-b]pyridine-5-carboxamide, N-[( 2,3-Dichlorophenyl)methyl]-1-ethyl-4-[(4-ketocyclohexyl)amino]pyrazolo[3,4-b)pyridine-5-carboxamide, N-[(3-Chloro-4-methylphenyl)methyl]sodiumethyl-[(4-ketocyclohexyl)amino]-1Η-pyrazolo[3,4-b]pyridine- 5-carbamamine, N-[(4-carbyl-2-methylphenyl) Methyl]sodiumethyl-4-[(4-ketocyclohexyl)amino]-1Η-pyrazolo[3,4-b]pyridine-5·carboxamide, 87841-960303.doc -62- 1283678 N-[(2,4-Dimethylphenyl)methyl]-1-ethyl-4-{[4-(hydroxyimino)cyclohexyl]amino}-1Η_pyrazolo[3 , 4_b]pyridine-5-carbamide, Ν·[(3,4-dimethylphenyl)methyl]-1-ethyl-4-{[4-(hydroxyimino)cyclohexyl]amine }}-Η-pyrazolo[3,4-b]pyridine-5-formamide, N-[(2,3-dichlorophenyl)methyl]small ethyl bucket {[hydroxyimino) Cyclohexyl]amino}-1Η-pyrazolo[3,4-b]pyridine-5-formamide, Ν-[(3·chloro-4-4-methylphenyl)methyl] succinate- 4_{[4_(Imino)cyclohexyl]amino}-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, N-[(4-chloro-2-methyl) Phenyl)methyl]-1-ethyl-4-{[4·(hydroxyimino)cyclohexyl]amino}-1Η-pyrazolo[3,4-b]pyridine_5-formamide , N-({4-[(difluoromethyl)oxy)phenyl}methyl)methylethyl 4-{[4-(imido)cyclohexyl]amino}·1Η-pyrazole And [3,4-b]pyridine-5-formamide, or 1-ethyl ice {[4-(transamido)cyclohexyl]amino}_Ν_{[4·(trifluoromethyl)benzene Methyl}·1Η _ pyrazolo[3,4-b]pyridine-5-formamide; or a salt thereof. 52. A compound or salt according to claim 1 of the patent application, which is: N-[(2,4-dimercaptophenyl)methyl]sodiumethyl-4-[(4-ketocyclohexyl) Amino]-1H-indolo[3,4-b]pyridine-5-carboxamide, N-[(3,4-dimethylphenyl)methyl]_1_ethyl-4·[( 4-ketocyclohexyl)amino]-1H-indazolo[3,4-b]pyridyl-5-carbamamine, 1-ethyl-Ν-{[4·(methoxy)phenyl ]methyl}-4-[(4-ketocyclohexyl)amino]-1Η-azolo[3,4-b]pyridine-5-carboxamide, N-({4·[(difluoro) Methyl)oxy]phenyl}methyl)methylethyl 4-[(4-ketocyclohexyl)amino]-1Η-pyrazolo[3,4-b]pyridine_5-carboxamide , 87841-960303.doc -63- 1283678 4-(cyclohexylamino)-1-ethyl-N-{[4-(methoxy)phenyl]methyl}-1Η-ρ than gorge [3 ,4-b]pyridine-5-methanamine, N_[(3-chlorobendenylmethyl)methyl]_1_ethyl-4_(tetrahydro-2H-piperazin-4-ylamino) -1Η-pyrazolo[3,4-b]pyridine_5. formamide, N-[(4-chloro-2-methylphenyl)methyl]-1-ethyl winter (tetrahydro- 2H·piperidinylamino)_1Η-pyrazolo[3,4-b]pyridine-5-carbamimidamine, N-[(3,4-dimethylphenyl)methyl]butylethyl- 4 _(tetrahydro-2H-piperidinylamino)-1Η-pyrazolo P,4-b]pyridine-5-carboxamide, 1-ethyl-N-[(4-methylphenyl) Methyl]·4-(tetrahydro-2H-piperidin-4-ylamino)-m-oxazolo[3,4-b]pyridine-5-carboxamide, N-[(2,4- Dimethylphenyl)methyl]-1-ethyl_4·(tetrazo-2H-pyran-4-ylamino group than spit[3,4-b] outside 1:di-5-branched Amine, N-[(2,3-diphenyl)methyl]-1.ethyl-4-(tetra-argon-; 2H-piperidin-4-ylamino)-1Η-external oxime [ 3,4-b]pyridine-5-carboxamide, N_{[2,3-dichloro-6.(methyl)phenyl]methyl}-1-ethyl-4-(tetrahydro-2H -piperazin-4-ylamino)-1Η·pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-4-{[4_(hydroxyimino)cyclohexyl] Amino}-N-{[4-(methoxy)phenyl]methyl}-1Η_ρ is 唆[3,4-b]p than _5·carbamamine, N-[(4-气-2-methylphenyl)methyl]-1-ethyl-4-[(4-ketocyclohexyl)amino]·1Η-pyrazolo[3,4-b]pyridine-5-rebel Amine, N-[(2,4-methylphenyl)methyl]-1-ethyl-4·{[4-(imido)cyclohexyl]amino}-1Η-pyrazolo[ 3,4-b]pyridine-5-carboxamide, N-[(3,4-methylphenyl)methyl]-1-ethyl_4-{ [4-(transamido)cyclohexyl]amino}}1Η-ρ is 唆[3,4-b]^: bite-5-myramine, 87841-960303.doc -64- 1283678 N- [(2,3-dichlorophenyl)methyl]-oxime-ethyl_heart {[4_(hydroxyimino)cyclohexyl]amino}}Η^^^^[3,4-b]p Bishen-5-carboxamide, N-[(3-chloro-4-methylphenyl)methyl]ethyl_heart {[4-(hydroxyimino)cyclohexyl]amino}-1Η- Pyrazolo[3,4-b]pyridine-5-carboxamide, Ν·[(4-chloro-2-methylphenyl)methyl]_丨-ethyl_4-{[4-(hydroxy Imino)cyclohexyl]amino}-1Η·pyrazolo[3,4-b]pyridine-5-carboxyguanamine, N-({4-[(difluoromethyl)oxy]phenyl} Methyl)-1_ethyl-4-{[4-(hydroxyimino)cyclohexyl]amino}}1Η-ρ ratio 4 and [3,4-b]p than lake-5-rebel amine Or 1-ethyl-4-{[4-(hydroxyimino)cyclohexyl]amino}-N_{[4-(trifluoromethyl)phenyl]methyl}-1Η-pyrazolo[ 3,4-b]pyridine-5-carboxyguanamine; or a salt thereof. 53. A compound or salt according to claim 1 of the patent application, which is: N-benzyl-1-ethyl-4_(tetrahydro-2-indole-piperidin-4-ylamino)-1Η-pyrazole [3,4-b]p is more than a 5-amine, 1_ethyl-Ν·(4·fluorophenyl)-4-(tetrahydro-2H_^-yl-4-ylamino)-1Η -pyrazolo[3,4-b]pyridine-5-carboxamide, 1-ethyl-N-ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1Η-pyridyl Zoxa[3,4_b]pyridine-5-carboxamide, 1-ethyl-indole-[4·(methylsulfonyl)-yl]·4_(tetrahydro-2H-pyran-4-ylamine -1Η-pyrazolo[3,4-b]pyridine-5-carboxyguanamine, 1-ethyl-4_(tetrahydro-:2H-hamo-4-ylamino)-Ν-(1 , 3-Deta-2-ylmethyl)-1Η-pyrazolo[3,4-b]pyridine-5-carboxamide, N-(3,4-dimethoxybenzyl)1-ethyl- 4_(tetrahydro-2H_bromo-4-ylamino)_1H-pyrazolo[3,4-b]pyridine-5-carboxyguanamine, 87841-960303.doc -65- 1283678 卜乙_N-{ 4-[(Methylsulfonyl)methyl]phenyl}-4-(tetrahydro-2H-piperidin-4-ylamino)-1Η-pyrazolo[3,4-b]pyridine-5 - Carboxylamamine, 1 · Ethyl-hydrazine·[(1_Methyl-iH-p to ton-4-yl) fluorenyl]-4-(tetrahydro-2H-pyran-4-ylamino) -1Η-ρ比峻和[3,4 _b]p than lake-5-carboxylic acid amine, or puethyl-N-(2-pyridylmethyl)-4-(tetrahydro-2H·jungan-4-ylamino)-1Η-pyrazolo[ 3,4-b]pyridine-5-carboxyguanamine; or a salt thereof. 54. A compound or salt according to any one of claims 1 to 3, 6, 7, 9, 10, 11, 19, 26 to 33, 51, 52 or 53 which is a compound or a pharmaceutical thereof Acceptable salt. 55. A compound or salt according to any one of claims 1 to 3, 6, 7, 9, 10, 11, 19, 26 to 33, 51, 52 or 53 which is in the form of a particle size reduction. 56. A compound or salt according to claim 55, wherein the reduced size of the compound or salt has a particle size (D5〇) of from 0.5 to 1 μm. 57. A compound or salt according to any one of claims 1 to 3, 6, 7, 9, 10, u, 19, % to 33, 51, 52 or 53 as a human phosphodiesterase 4 inhibitors. 58. A pharmaceutical composition comprising as defined in any one of claims 1 to 3, 6, 7, 9, 10, 11, 19, 26 to 33, 5, 52 or 53 &lt; Compound of Formula (I) or (IA) or (IB), or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers and/or excipients, wherein the composition is as a phosphoric acid Diesterase 4 inhibitors for treatment and/or prevention: human asthma, chronic bronchitis, emphysema, atopic dermatitis, urticaria, allergic nasal 87841-960303.doc -66- 1283678 inflammation, allergic binding membrane Inflammation, spring combined with membranous inflammation, sputum red granuloma, psoriasis, f arthritis, septic shock, ulcerative colitis, Crohn's disease, myocardial and brain reperfusion injury, chronic spheroid Nephritis, endotoxin shock, adult dyspnea syndrome or multiple sclerosis. 59. A pharmaceutical composition comprising, as claimed in claims 1 to 3, 6, 7, 9, 10, 11, 19, 26 to 33 a compound of formula (I) or (IA) or (IB), or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, as defined in any one of 5, 52 or / or an excipient wherein the composition is for the treatment and/or prevention of inflammatory and/or allergic diseases in humans. 60. - Formula 1 or (ia) as defined in any of the i-third to three, six, seven, nine, one, u, 19, 26 to 33' 5, 52 or 53 patent applications. Or the use of the (IB) compound or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the treatment and/or prevention of inflammatory and/or allergic diseases in humans. 61. According to the combination of the patent application No. 59 The composition, wherein the composition is for the treatment and/or prevention of chronic obstructive pulmonary disease (C〇pd), asthma or allergic rhinitis in humans. 62. The use according to claim 60, wherein the medicament is for treatment and/or Prevention of human fecal obstructive pulmonary disease (COPD), asthma or allergic rhinitis. 63. A combination comprising 1 to 3, 6, 7, 9, 10, 11, 19, 26 to 33, 51 according to the scope of the patent application. a compound of formula (I) or (IA) or (IB), or a pharmaceutically acceptable salt thereof, as defined in any one of 52 or 53 above, and an adrenergic receptor agonist, an antihistamine, an antiallergic or Anti-inflammatory agent. 64. A combination comprising, according to the scope of the patent application No. 3, 6, 7, 9, 10, 11, 19, 26 to 33, 51, 52 87841-960303.doc -67 - 1283678, or a compound of formula (I) or (IB) or a pharmaceutically acceptable salt thereof, and a muscarine (M) receptor, as defined in any one of 53 Antagonist. 65. A combination according to claim 64, wherein the muscarine (M) receptor antagonist is an M3 receptor antagonist. 87841-960303.doc 68-