1h-pyrrolo[2,3-b] pyridine derivatives and their use as kinase inhibitors

Abstract

The inventions relates to compounds of (I) and therapeutic uses thereof: (I) The terms Z, Y, and R1 are as defined in the claims.

1 . A compound of formula I: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 each Z is independently (Alk) n -R n -(Alk) n -X, 
 wherein each Alk is independently (C 1  to C 12 ) alkylene or (C 2  to C 12 ) alkenylene, each of which may be optionally substituted; 
 each n is independently 0 or 1; 
 each R is independently optionally substituted arylene or heteroarylene, or optionally substituted cycloalkylene or heterocyclic, —O—, —S—, —(C═O)—, —(C═S)—, —SO 2 —, —C(═O)O—, —C(═O)NR A —, —C(═S)NR A —, —SO 2 NR A —, —NR A C(═O)—, —NR A SO 2 — or —NR A — wherein R A  is hydrogen, C 1 -C 6  alkyl, —C 1 -C 6  alkyl(cycloalkyl), C 1 -C 6  alkyl(C 1 -C 6  alkoxy) or C 1 -C 6  alkoxy; 
 each X is independently halogen, —H, —OR A , NR A R A , optionally substituted aryl or heteroaryl, or optionally substituted cycloalkyl or heterocyclic, CN or C(halogen) a H b , where a is 1, 2, or 3, and b is (3-a); 
 Y is optionally substituted acyl or heteroaryl, or optionally substituted cycloalkyl; and 
 R 1  is H or C 1 -C 6  alkyl. 
 
     
     
         2 - 18 . (canceled) 
     
     
         19 . A method of inhibiting CHK1 activity in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of  claim 1 . 
     
     
         20 - 24 . (canceled) 
     
     
         25 . A process for the preparation of a compound of formula (I): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, 
       said process comprising the step of reacting a compound of formula (II) with a compound of formula (III) to form the compound of formula (I) 
       
         
           
           
               
               
           
         
       
       wherein:
 each Z is independently (Alk) n -R n -(Alk) n -X, 
 each Alk is independently (C 1  to C 12 ) alkylene or (C 2  to C 12 ) alkenylene, each of which may be optionally substituted; 
 each n is independently 0 or 1; 
 each R is independently optionally substituted arylene or heteroarylene, or optionally substituted cycloalkylene or heterocyclic, —O—, —S—, —(C═O)—, —(C═S)—, —SO 2 —, —C(═O)O—, —C(═O)NR A —, —C(═S)NR A —, —SO 2 NR A —, —NR A C(═O)—, —NR A SO 2 — or —NR A — wherein R A  is hydrogen, C 1 -C 6  alkyl, —C 1 -C 6  alkyl(cycloalkyl), C 1 -C 6  alkyl(C 1 -C 6  alkoxy) or C 1 -C 6  alkoxy; 
 each X is independently halogen, —H, —OR A , NR A R A , optionally substituted aryl or heteroaryl, or optionally substituted cycloalkyl or heterocyclic, CN or C(halogen) a H b , where a is 1, 2, or 3, and b is (3-a); 
 Y is optionally substituted aryl or heteroaryl, or optionally substituted cycloalkyl or heterocyclic; and 
 R 1  is H or C 1 -C 6  alkyl. 
 
     
     
         26 . The process as claimed in  claim 25 , wherein the compound of formula (II) is reacted with the compound of formula (III) in the presence of a coupling agent and a base to form the compound of formula (II). 
     
     
         27 . The process as claimed in  claim 26 , wherein the coupling agent is HATU and the base is trimethylamine. 
     
     
         28 . The process as claimed in  claim 25 , wherein a compound of formula (II) is formed by reacting a compound of formula (IV) with a reducing agent 
       
         
           
           
               
               
           
         
       
       wherein Z is as defined in  claim 25 . 
     
     
         29 . The process as claimed in  claim 28 , wherein the reducing agent is tin (II) chloride dihydrate. 
     
     
         30 . The process as claimed in  claim 28 , wherein the compound of formula (IV) is formed by reacting a compound of formula (V): 
       
         
           
           
               
               
           
         
       
       with nitric acid, 
       wherein Z is as defined in  claim 25 . 
     
     
         31 . The process as claimed in  claim 25 , wherein Y is not phenyl substituted with O-methyl. 
     
     
         32 . The process as claimed in  claim 25 , wherein R A  is hydrogen or C 1 -C 6  alkyl. 
     
     
         33 . The process as claimed in  claim 25 , wherein at least one Z is H, halogen, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted nitrogen-containing heterocycle, C 1  to C 6  alkyl, or OR A . 
     
     
         34 . The process as claimed in  claim 33 , wherein one Z group is H, halogen, OR A  or C 1  to C 6  alkyl, and the other Z group is optionally substituted aryl or optionally substituted nitrogen-containing heterocycle. 
     
     
         35 . The process as claimed in  claim 34 , wherein the nitrogen-containing heterocycle is substituted with NR A R A . 
     
     
         36 . The process as claimed in  claim 25 , wherein at least one Z is (Alk) n -optionally substituted aryl ene-(Alk) n -optionally substituted heterocycle. 
     
     
         37 . The process as claimed in  claim 25 , wherein R 1  is H. 
     
     
         38 . The process as claimed in  claim 25 , wherein R 1  is C 1 -C 6  alkyl that comprises a cycloalkyl portion. 
     
     
         39 . The process as claimed in  claim 25 , wherein Y is phenyl or heteroaryl optionally substituted with C 1  to C 6  alkyl, OR A , halogen or C 1  to C 6  alkoxy. 
     
     
         40 . The process as claimed in  claim 39 , wherein Y is pyridyl, pyrrolyl, phenyl, or phenyl substituted with methyl, bromine or chlorine. 
     
     
         41 . The process as claimed in  claim 25 , wherein the compound of formula (I) is a compound of formula (Ia): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 Z 1  and Z 2  are independently (Alk) n -R n -(Alk) n -X; and 
 Alk, n, R, X, Y, R A  and R 1  are as defined in  claim 25 . 
 
     
     
         42 . The process as claimed in  claim 41 , wherein Z 1  is halogen, phenyl, OR A  or C 1  to C 6  alkyl, and Z 2  is optionally substituted aryl or optionally substituted heterocycle. 
     
     
         43 . The process as claimed in  claim 41 , wherein Z 2  is halogen, CF 3 , cyclopropyl, phenyl, OR A  or C 1  to C 6  alkyl, and Z 1  is optionally substituted aryl or optionally substituted heterocycle. 
     
     
         44 . The process as claimed in  claim 41 , wherein the heterocycle or nitrogen-containing heterocycle is an optionally substituted piperidine, piperazine or morpholine. 
     
     
         45 . The process as claimed in  claim 25 , wherein the compound of formula (I) is one of the compounds listed below, or a pharmaceutically acceptable salt thereof:
 1-Benzyl-1H-pyrazole-4-carboxylic acid (5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid (1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid (4-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide,   1-Benzyl-1H-pyrazole-4-carboxylic acid (5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide,   1-Benzyl-1H-pyrazole-4-carboxylic acid (5-piperidin-1-yl-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;   N-{4-[(3R)-3-Aminopiperidin-1-yl]-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl}-1-benzyl-1H-pyrazole-4-carboxamide,   1-Benzyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-pyrrolidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [5-bromo-4-((R)-3-methylamino-piperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [5-bromo-4-((R)-3-ethylamino-piperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [5-bromo-4-((R)-3-hydroxy-pyrrolidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [5-bromo-4-((R)-3-hydroxy-piperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [5-bromo-4-(3-dimethylamino-piperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid {5-bromo-4-[(R)-3-(cyclopentylmethyl-amino)-piperidin-1-yl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [5-bromo-4-((R)-3-isobutylamino-piperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid {5-bromo-4-[(R)-3-(2,2-dimethyl-propylamino)-piperidin-1-yl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide   1-Benzyl-1H-pyrazole-4-carboxylic acid {5-bromo-4-[(R)-3-(cyclopropylmethyl-amino)-piperidin-1-yl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;   1-(4-Fluoro-benzyl)-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-(4-Chloro-benzyl)-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-(4-Methyl-benzyl)-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-(4-Methoxy-benzyl)-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Pyridin-2-ylmethyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Pyridin-3-ylmethyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Pyridin-4-ylmethyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   N-{4-[(3R)-3-aminopiperidin-1-yl]-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl}-1-benzyl-1H-pyrazole-4-carboxamide;   1-(4-Methyl-benzyl)-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-(1-Fluoro-benzyl)-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-(4-Chloro-benzyl)-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-(4-Methoxy-benzyl)-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-pyrrolidin-1-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   N-{4-[(3R)-3-aminopiperidin-1-yl]-5-cyclopropyl-1H-pyrrolo[2,3-b]pyridin-3-yl}-1-benzyl-1H-pyrazole-4-carboxamide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-hydroxy-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [5-(4-piperidin-1-ylmethyl-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [5-(4-{[(2-methoxy-ethyl)-methyl-amino]-methyl}-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [5-(4-pyrrolidin-1-ylmethyl-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[4-(4-fluoro-piperidin-1-ylmethyl)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [5-(4-dimethylaminomethyl-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[4-(3-fluoro-piperidin-1-ylmethyl)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [5-(4-methylaminomethyl-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [5-(4-morpholin-4-ylmethyl-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[4-(3,3-difluoro-pyrrolidin-1-ylmethyl)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [5-(3-dimethylaminomethyl-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[3-(3-fluoro-piperidin-1-ylmethyl)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[3-(3,3-difluoro-piperidin-1-ylmethyl)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [5-(3-azetidin-1-ylmethyl-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[3-(3,3-difluoro-azetidin-1-ylethyl)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [5-(5-pyrrolidin-1-ylmethyl-thiophen-2-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [5-(5-pyrrolidin-1-ylmethyl-thiophen-3-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[5-(3,3-difluoro-azetidin-1-ylmethyl)-thiophen-3-yl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [5-(3-pyrrolidin-1-ylmethyl-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-cyano-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[3-(2-morpholin-4-yl-ethoxy)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[3-(3-dimethylamino-2,2-dimethyl-propoxy)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[3-(3-morpholin-4-yl-propoxy)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[3-(1-methyl-piperidin-3-ylmethoxy)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[3-(oxetan-3-yloxy)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[3-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [4-((3R,4R)-3-amino-4-cyclopropyl-piperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [5-(2-fluoro-4-pyrrolidin-1-ylmethyl-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [5-(3-pyrrolidin-1-yl-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid (5-pyridin-4-yl-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid (5-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;   1-(3-Methoxy-benzyl)-1H-pyrazole-4-carboxylic acid (5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;   1-(2-Fluoro-benzyl)-1H-pyrazole-4-carboxylic acid (5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;   1-(2-Cyano-benzyl)-1H-pyrazole-4-carboxylic acid (5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;   1-(1H-Pyrrol-2-ylmethyl)-1H-pyrazole-4-carboxylic acid (5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;   1-(4-Fluoro-benzyl)-1H-pyrazole-4-carboxylic acid (5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid (5-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid (5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;   1-(4-Fluoro-benzyl)-1H-pyrazole-4-carboxylic acid (5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;   1-(3-Methoxy-benzyl)-1H-pyrazole-4-carboxylic acid (5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[3-((S)-1-methyl-pyrrolidin-2-ylmethoxy)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[3-(1-methyl-piperidin-3-yloxy)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[4-(3-dimethylamino-propoxy)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[1-(2-diethylamino-ethyl)-1H-pyrazol-4-yl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid {5-[1-(2-pyrrolidin-1-yl-ethyl)-1H-pyrazol-4-yl]-1H-pyrrolo[2,3-b]pyridin-3-y}-amide;   1-Pyridin-4-ylmethyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Pyridin-3-ylmethyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Pyridin-2-ylmethyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Pyridin-3-ylmethyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Pyridin-4-ylmethyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Pyridin-2-ylmethyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Pyridin-4-ylmethyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Pyridin-3-ylmethyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-(4-Fluoro-benzyl)-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-(3-Methyl-benzyl)-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-(3-Fluoro-benzyl)-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-(2-Chloro-benzyl)-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-(2-Methyl-benzyl)-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-(4-Fluoro-benzyl)-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Benzyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Pyridin-3-ylmethyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide;   1-Pyridin-2-ylmethyl-1H-pyrazole-4-carboxylic acid [4-((R)-3-amino-piperidin-1-yl)-5-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-amide.