IP Library › Granted Patent US 10,000,481

Granted Patent B2

US 10,000,481 · App. 14/375,353 · Granted Jun 19, 2018

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

Inventors: Stephen Stokes (Winnersh, GB); Christopher John Graham (Winnersh, GB); Stuart Christopher Ray (Winnersh, GB); Emma Jayne Stefaniak (Winnersh, GB)

Assignee: Vernalis (R&D) Limited

C07D471/04 A61K31/437 A61K31/4545 A61K45/06

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Quick Facts

Patent No.: US 10,000,481
App. No.: 14/375,353
Granted: Jun 19, 2018
Kind: B2

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Abstract

The inventions relates to compounds of (I) and therapeutic uses thereof: (I) The terms Z, Y, and R 1 are as defined in the claims.

Claims (212)

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 is optionally substituted;

each n is independently 0 or 1;

each R is independently optionally substituted arylene, optionally substituted heteroarylene optionally substituted cycloalkylene, optionally substituted 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; and

each X is independently halogen, —H, —OR A , NR A R A , optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl optionally substituted heterocyclic, CN or C(halogen) a H b , where a is 1, 2, or 3, and b is (3-a);

Y is phenyl optionally substituted with C 1 to C 6 alkyl or halogen; optionally substituted, bicyclic or tricyclic aryl; optionally substituted heteroaryl; optionally substituted cycloalkyl; or optionally substituted heterocycle; and

R 1 is H or C 1 -C 6 alkyl.

2. The compound according to claim 1 , wherein R A is hydrogen or C 1 -C 6 alkyl.

3. The compound according to claim 1 , 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 .

4. The compound according to claim 3 , 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.

5. The compound according to claim 4 , wherein the nitrogen-containing heterocycle is substituted with NR A R A .

6. The compound according to claim 1 , wherein at least one Z is (Alk) n -optionally substituted arylene-(Alk) n -optionally substituted heterocycle.

7. The compound according to claim 1 , wherein R 1 is H.

8. The compound according to claim 1 , wherein C 1 to C 6 alkyl includes a cycloalkyl portion.

9. The compound according to claim 1 , wherein Y is phenyl optionally substituted with C 1 to C 6 alkyl or halogen, or heteroaryl optionally substituyed with C 1 to C 6 alkyl, OR A , halogen or C 1 to C 6 alkoxy.

10. The compound according to claim 9 , wherein Y is pyridyl, pyrrolyl, phenyl, or phenyl substituted with methyl, bromine or chlorine.

11. The compound according to claim 1 , wherein the compound is of the formula Ia:

or a pharmaceutically acceptable salt thereof, wherein:

Z 1 and Z 2 are independently (Alk) n -R n -(Alk) n -X.

12. The compound according to claim 11 , 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.

13. The compound according to claim 11 , 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.

14. The compound according to claim 11 , wherein the heterocycle is an optionally substituted piperidine, optionally substituted piperazine,or optionally substituted morpholine.

15. A compound according to claim 1 , wherein the compound 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-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-(4-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-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-ylmethyl)-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-(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-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-yl}-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; and

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.

16. A pharmaceutical composition comprising 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, optionally substituted heteroarylene, optionally substituted cycloalkylene, optionally substituted 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; and

each X is independently halogen, —H, —OR A , NR A R A , optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclic, CN or C(halogen) a H b , where a is 1, 2, or 3, and b is (3-a);

R 1 is H or C 1 -C 6 alkyl,

and one or more pharmaceutically acceptable carriers and/or excipients.

17. The pharmaceutical composition according to claim 16 , 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 .

18. The pharmaceutical composition according to claim 16 , wherein R 1 is H.

19. The pharmaceutical composition according to claim 16 , 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.

20. The compound according to claim 10 , wherein Y is phenyl.

21. The compound according to claim 1 , wherein Y is phenyl optionally substituted with C 1 to C 6 alkyl or halogen.

22. The compound according to claim 1 , wherein the compound 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-l-yl-1H-pyrrolo[2,3-b]pyridin-3-yl)-amide;

N-{14-[(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-y}-amide;