IP Library Granted Patent US 9,096,598
Granted Patent B2
US 9,096,598 · App. 14/349,377 · Granted Aug 4, 2015

Azaindoles as Janus kinase inhibitors

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Quick Facts
Patent No.
US 9,096,598
App. No.
14/349,377
Granted
Aug 4, 2015
Kind
B2
Abstract

The instant invention provides compounds of formula I which are JAK inhibitors, and as such are useful for the treatment of JAK-mediated diseases such as rheumatoid arthritis, asthma, COPD and cancer.

Claims (167)

1. A compound of formula I

or a pharmaceutically acceptable salt thereof; wherein L is chosen from:

wherein L is substituted with 0, 1, 2, or 3 independently chosen R 5 ;

W is chosen from C 1-10 alkylamino, a 3-15 member saturated, unsaturated or partially saturated monocyclic or bicyclic ring system containing 0, 1, 2, 3, or 4 atoms independently selected from N, O, or S, and —NR 6 R 6 wherein two R 6 and the nitrogen to which they are attached can optionally form a -4, -5, or -6 member saturated ring system, and wherein W is substituted with 0, 1, 2 or 3 independently chosen R 5 ;

Calkoxy,

C alkylsulfonyl,

(C alkyl)sulfonylamino,

R 6 is independently selected from:

hydrogen,

(carbonyl) 0-1 C 1-10 alkyl,

(carbonyl) 0-1 C 2-10 alkenyl,

(carbonyl) 0-1 C 2-10 alkynyl,

C 0-10 alkylcarbonyl(oxy) 0-1 C 0-10 alkyl,

C 1-10 alkyl(oxy) 0-1 carbonylC 0-10 alkyl,

C 2-10 alkenylcarbonyl,

C 2-10 alkynylcarbonyl,

(C 1-10 )alkyl(oxy) 0-1 C 0-10 alkyl,

aryl(oxy) 0-1 C 0-10 alkyl,

(C 3-8 )heteroaryl(oxy) 0-1 C 0-10 alkyl,

C 3-8 cycloalkyl(oxy) 0-1 C 0-10 alkyl,

(C 3-8 )heterocycloalkyl(oxy) 0-1 C 0-10 alkyl,

(C 1-10 )heteroalkyl(oxy) 0-1 C 0-10 alkyl,

C 0-10 alkyl(oxy) 0-1 C 0-10 alkylaminocarbonylC 0-10 alkyl,

C 0-10 alkylaminocarbonylC 1-10 heteroalkyl,

C 0-10 alkylaminocarbonyl(C 3-8 )heterocycloalkylC 0-10 alkyl,

C 0-10 alkylaminocarbonyl(C 3-8 )heteroarylC 0-10 alkyl,

C 0-10 alkylaminocarbonyl(C 3-8 )cycloalkylC 0-10 alkyl,

C 0-10 alkylaminocarbonylarylC 0-10 alkyl,

hydroxy C 0-10 alkyl,

C 0-10 alkylsulfonyl,

aryl C 1-10 alkylsulfonyl,

C 3-8 heterocyclyl C 1-10 alkylsulfonyl,

C 3-8 heterocycloalkyl C 1-10 alkylsulfonyl,

C 3-8 cycloalkyl C 1-10 alkylsulfonyl, and

C 1-6 haloalkyl;

R 1 , R 2 and R 5 are independently chosen from (1-methylethyl)carbamoyl, (2-methoxyethyl)carbamoyl, (2-hydroxy-ethyl)carbamoyl, (tetrahydro-2H-pyran-4-yl)carbamoyl, azetidin-1-ylcarbonyl, 2-methylpropylcarbamoyl, carbamoyl, (tetrahydrothiophen-3-yl)carbamoyl, (1H-pyrazol-5-ylmethyl)carbamoyl, (4-hydroxypiperidin-1-yl)carbonyl, cyclopropylmethylcarbamoyl, sulfamoyl, dimethylsulfamoyl, amino, acetylamino, sulfonylamino, propanoylamino, (propan-2-ylcarbamoyl)amino, (propylcarbamoyl)amino, carbamoylamino, methylcarbamate, ethylcarbamate, (1-methylethyl)carbamate, 1H-pyrazolyl, tertbutoxymethyl, (methoxyethyl)piperazinyl, 2-morpholin-4-ylethoxy)methyl, (prop-2-en-1-yloxy)methyl, piperidinylmethoxy, pyrrolidin-1-ylmethyl, methoxymethyl, cyclopentanylcarboxamidomethyl, propanoylamino)methyl, (cyclohexanecarbonylamino)methyl, but-2-enoylaminomethyl, (cyclopropylcarbonyl)aminomethyl, (1,3-oxazol-5-yl)carbonylaminomethyl, (butanoylamino)methyl, (pyrrolidin-1-ylcarbonyl)aminomethyl, halogen, cyano, carbamoyl, methoxy, trifluoroethyl, methylsulfonyl, hydroxyl, 2-methoxyethoxy, methylethoxy, benzyloxy, cyclopentyloxy, cyclopropylmethoxy, 2-phenylethoxy, 2,3-dihydro-1H-inden-2-yloxy, tetrahydro-2H-pyran-4-yloxy, 2-oxopyrrolidin-1-yl)ethoxy, pyridin-3-ylmethoxy, 2-pyridin-2-ylethoxy, 2-(dimethylamino)ethoxy, 3-(dimethylamino)propoxy, 2-morpholin-4-ylethoxy, 1-methylpiperidin-4-yl)oxy, 2-(piperazin-1-yl)ethoxy, hydrogen, and piperidin-4-yl)methoxy, wherein R 1 , R 2 and R 5 are independently substituted with 0, 1, 2, or 3 substituents R 3 ;

wherein R 1 , R 2 , R 5 and R 6 are independently substituted with 0, 1, 2, or 3, substituents R 3 chosen from: halogen, C 1 -C 10 alkyl, CF 3 , NH 2 , N(C 1 -C 6 alkyl) 2 , NO 2 , —(C 0-6 )alkylCN, —OH, —O(C 1 -C 6 alkyl), C 3 -C 10 cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, (C 0 -C 6 alkyl) S(O) 0-2 —, (C 0 -C 6 alkyl)S(O) 0-2 (C 0 -C 6 alkyl)-, (C 0 -C 6 alkyl)C(O)NH—, H 2 N—C(NH)—, —O(C 1 -C 6 alkyl)CF 3 , (C 0 -C 6 alkyl)C(O)—, (C 0 -C 6 alkyl)OC(O)—, (C 0 -C 6 alkyl)O(C 1 -C 6 alkyl)-, (C 0 -C 6 alkyl)C(O) 1-2 (C 0 -C 6 alkyl)-, (C 0 -C 6 alkyl)OC(O)NH—, —NH(C 1 -C 6 alkyl)NHC(O)NH(C 1 -C 6 alkyl), NHC(O)OC 1 -C 6 alkyl, —NH(C 1 -C 6 alkyl)NHSO 2 (C 1 -C 6 alkyl), —(C 0 -C 6 alkyl)NHSO 2 (C 1 -C 6 alkyl), C 1-10 alkoxy, —CO 2 (C 0-10 alkyl), Oxo (═O), trifluoromethyl, trifluoroethyl, C 1-10 alkylsulfonyl, —SO 2 N(C 1-6 alkyl) 1-2 , —SO 2 CF 3 , —SO 2 CF 2 H, —C 1-10 alkylsulfinyl, —O (0-1) (C 1-10 )haloalkyl, aryl, heteroaryl, heterocyclyl, halo-aryl, halo-heterocyclyl, cyano-aryl, cyano-heteroaryl, and cyano-heterocyclyl.

2. A compound according to claim 1 , wherein W is chosen from C 1-10 alkylamino, and —NR 6 R 6 , wherein two R 6 and the nitrogen to which they are attached can optionally form a -4, -5, or -6 member saturated ring system and wherein W is substituted with 0, 1, 2 or 3 independently chosen R 5 .

3. A compound according to claim 1 wherein W is chosen from a 3-15 member saturated, unsaturated or partially saturated monocyclic or bicyclic ring system containing 0, 1, 2, 3, or 4 atoms independently selected from N, O, or S, —NR 6 R 6 wherein two R 6 and the nitrogen to which they are attached can optionally form a -4, -5, or -6 member saturated ring system, and wherein W is substituted with 0, 1, 2 or 3 independently chosen R 5 .

4. A compound selected from the group consisting of:

(2R)-2-{[5-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]amino}-3-methyl-N-(2,2,2-trifluoroethyl)butanamide;

2-{[5-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3yl)pyridin-3-yl]amino}-3-methyl-N-(2,2,2-trifluoroethyl)butanamide;

N˜2˜-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-1,2,4-triazin-5-yl]-N-(2,2,2-trifluoroethyl)-D-valinamide;

7-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-1,2,4-triazin-5-yl]-8-methyl-3-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine;

5-chloro-3-{5-[2-(1,3-thiazol-2-yl)pyrrolidin-1-yl]-1,2,4-triazin-3-yl}-1H-pyrrolo[2,3-b]pyridine;

N˜2˜-[3-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-1,2,4-triazin-5-yl]-2-methyl-N-(2,2,2-trifluoroethyl)alaninamide;

N˜-2˜-[3-(5-cyano-1H-pyrrolo[2,3-b]pyridin-3-yl)-1,2,4-triazin-5-yl]-2-methyl-N-(2,2,2-trifluoroethyl)alaninamide;

N˜2˜-[3-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-1,2,4-triazin-5-yl]-N-(2,2,2-trifluoroethyl)-D-alaninamide;

N˜2˜-[3-(5-cyano-1H-pyrrolo[2,3-b]pyridin-3-yl)-1,2,4-triazin-5-yl]N-(2,2,2-trifluoroethyl)-D-alaninamide;

7-[3-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-1,2,4-triazin-5-yl]-8-methyl-3-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine;

5-fluoro-3-{5-[2-(1,3-thiazol-2-yl)pyrrolidin-1-yl]-1,2,4-triazin-3-yl}-1H-pyrrolo[2,3-b]pyridine;

3-{5-[2-(1,3-thiazol-2-yl)pyrrolidin-1-yl]-1,2,4-triazin-3-yl}-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile;

3-[5-({1,1-dimethyl-2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl}amino)-1,2,4-triazin-3-yl]-1H-pyrrolo[2,3-b]pyridine-5-carboxamide;

3-[5-({(1R)-1-methyl-2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl}amino)-1,2,4-triazin-3-yl]-1H-pyrrolo[2,3-b]pyridine-5-carboxamide;

3-{5-[8-methyl-3-(trifluoromethyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl]-1,2,4-triazin-3-yl}-1H-pyrrolo[2,3-b]pyridine-5-carboxamide;

N˜2˜-[3-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-1,2,4-triazin-5-yl]-N-(2,2,2-trifluoroethyl)-D-valinamide;

N˜2˜-[3-(5-cyano-1H-pyrrolo[2,3-b]pyridin-3-yl)-1,2,4-triazin-5-yl]-N-(2,2,2-trifluoroethyl)-D-valinamide;

3-[5-({(1R)-2-methyl-1-[(2,2,2-trifluoroethyl)carbamoyl]propyl}amino)-1,2,4-triazin-3-yl]-1H-pyrrolo[2,3-b]pyridine-5-carboxamide;

(1S,2R)-2-{[3-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-1,2,4-triazin-5-yl]amino}-N-(2,2,2-trifluoroethyl)cyclohexanecarboxamide;

N˜2˜-[3-(5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)-1,2,4-triazin-5-yl]-N-(2,2,2-trifluoroethyl)-D-valinamide;

(1S,2R)-2-{([3-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-1,2,4-triazin-5-yl]amino}-N-(2,2,2-trifluoroethyl)cyclohexanecarboxamide;

(1S,2R)-2-{[3-(5-cyano-1H-pyrrolo[2,3-b]pyridin-3-yl)-1,2,4-triazin-5-yl]amino}-N-(2,2,2-trifluoroethyl)cyclohexanecarboxamide;

3-[5-({(1R,2S)-2-[(2,2,2-trifluoroethyl)carbamoyl]cyclohexyl}amino)-1,2,4-triazin-3-yl]-1H-pyrrolo[2,3-b]pyridine-5-carboxamide;

N˜2˜-[6-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridazin-4-yl]-N-(2,2,2-trifluoroethyl)-D-alaninamide;

N-(2,2,2-trifluoroethyl)-N˜2˜-{6-[5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridazin-4-yl)}-D-alaninamide;

5-chloro-3-{5-[2-(1,3-thiazol-2-yl)pyrrolidin-1-yl]pyridazin-3-yl}-1H-pyrrolo[2,3-b]pyridine;

N˜2˜-[5-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]-2-methyl-N-(2,2,2-trifluoroethyl)alaninamide;

5-chloro-3-{5-[2-(1,3-thiazol-2-yl)pyrrolidin-1-yl]pyridin-3-yl}-1H-pyrrolo[2,3-b]pyridine;

N˜2˜-[5-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]-N-(2,2,2-trifluoroethyl)-D-alaninamide;

N˜2˜-[5-(5-fluor-H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]-N-(2,2,2-trifluoroethyl)-D-alaninamide;

N˜2˜-[5-(5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]N-(2,2,2-trifluoroethyl)-D-alaninamide;

N˜2˜-[5-(5-cyano-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]-N-(2,2,2-trifluoroethyl)-D-alaninamide;

R)-2-{[5-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]amino}-N-(2,2,2-trifluoroethyl)cyclohexanecarboxamide;

N˜2˜-{5-[5-(methylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridin-3-yl}-N-(2,2,2-trifluoroethyl)-D-alaninamide;

2-[6-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrrolo[3,2-b]pyridin-1-yl]-N-(2,2,2-trifluoroethyl)propanamide;

N˜-2˜-[5-(5-chloro-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]-N-(2,2,2-trifluoroethyl)-D-alaninamide;

(1S,2R)-2-{[5-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]amino}-N-(2,2,2-trifluoroethyl)cyclohexanecarboxamide;

(1S,2R)-2-{[5-(5-cyano-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]amino}-N-(2,2,2-trifluoroethyl)cyclohexanecarboxamide;

N˜2˜-[5-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-fluoropyridin-3-yl]-N-(2,2,2-trifluoroethyl)alaninamide;

3-[5-({(1R,2S)-2-[(2,2,2-trifluoroethyl)carbamoyl]cyclohexyl}amino)pyridin-3-yl]-1H-pyrrolo[2,3-b]pyridine-5-carboxamide;

N˜2˜-[5-(5-cyano-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]-N-(2,2,2-trifluoroethyl)valinamide;

3-[5-({2-methyl-1-[(2,2,2-trifluoroethyl)carbamoyl]propyl}amino)pyridin-3-yl]-1H-pyrrolo[2,3-b]pyridine-5-carboxamide;

N˜2˜-[5-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]-2-methyl-N-(2,2,2-trifluoroethyl)alaninamide;

N˜2˜-[5-(5-cyan-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]-2-methyl-N-(2,2,2-trifluoroethyl)alaninamide;

N˜2˜-[5-(5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]-N-(2,2,2-trifluoroethyl)valinamide;

3-[5-({(1R)-1-methyl-2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl}amino)pyridin-3-yl]-1H-pyrrolo[2,3-b]pyridine-5-carboxamide;

3-[5-({1,1-dimethyl-2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl}amino)pyridin-3-yl]-1H-pyrrolo[2,3-b]pyridine-5-carboxamide;

2-{[5-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]amino}-2-cyclopropyl-N-(2,2,2-trifluoroethyl)acetamide;

N˜2˜-[5-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]-3-hydroxy-N-(2,2,2-trifluoroethyl)-D-valinamide;

3-hydroxy-N˜-2˜-[5-(5-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]-N-(2,2,2-trifluoroethyl)-D-valinamide;

N˜2˜-[5-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]-N-(2,22-trifluoroethyl)-D-valinamide;

N˜2˜-[5-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]-N-(2,22-trifluoroethyl)-L-valinamide;

2-{[5-(5-hydroxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]amino}-3-methyl-N-(2,2,2-trifluoroethyl)butanamide;

2-{[5-(5-hydroxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]amino}-3-methyl-N-(2,2,2-trifluoroethyl)butanamide;

N˜2˜-{5-[5-(1-methylethoxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridin-3-yl}-N-(2,2,2-trifluoroethyl)-D-valinamide;

N˜2˜-{5-[5-(benzyloxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridin-3-yl}-N-(2,2,2-trifluoroethyl)valinamide;

N˜2˜-5-[5-(cyclopentyloxy)-1H-pyrrolo[2,3-b]pyridine-3-yl]pyridin-3-yl)-N-(2,2,2-trifluoroethyl)valinamide;

N˜2˜-{5-[5-(cyclopropylmethoxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridin-3-yl}-N-(2,2,2-trifluoroethyl)valinamide;

N˜2˜-{5-[5-(2-phenylethoxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridin-3-yl}-N-(2,2,2-trifluoroethyl)valinamide;

N˜2˜-{5-[5-(2,3-dihydro-1H-inden-2-yloxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridin-3-yl}-N-(2,2,2-trifluoroethyl)valinamide;

N˜2˜-{5-[5-(tetrahydro-2H-pyran-4-yloxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridin-3-yl}-N-(2,2,2-trifluoroethyl)valinamide;

N˜2˜-(5-{5-[2-(2-oxopyrrolidin-1-yl)ethoxy]-1H-pyrrolo[2,3-b]pyridin-3-yl}pyridin-3-yl)-N-(2,2,2-trifluoroethyl)valinamide;

N˜2˜-{5-[5-(pyridin-3-ylmethoxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridin-3-yl}-N-(2,2,2-trifluoroethyl)valinamide;

N˜2˜-{5-[5-(2-pyridin-2-ylethoxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridin-3-yl}-N-(2,2,2-trifluoroethyl)valinamide;

N˜2˜-(5-{5-[2-(dimethylamino)ethoxy]-1H-pyrrolo[2,3-b]pyridin-3-yl}pyridin-3-yl)-N-(2,2,2-trifluoroethyl)valinamide;

N˜2˜-(5-{5-[3-(dimethylamino)propoxy]-1H-pyrrolo[2,3-b]pyridin-3-yl}pyridin-3-yl)-N-(2,2,2-trifluoroethyl)valinamide;

N˜2˜-{5-[5-(2-morpholin-4-ylethoxy)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridin-3-yl}-N-(2,2,2-trifluoroethyl)valinamide;

N˜2˜-(5-{5-[(1-methylpiperidin-4-yl)oxy]-1H-pyrrolo[2,3-b]pyridin-3-yl}pyridin-3-yl)-N-(2,2,2-trifluoroethyl)valinamide;

N˜2˜-(5-{5-[2-(4-methylpiperazin-1-yl)ethoxy]-1H-pyrrolo[2,3-b]pyridin-3-yl}pyridin-3-yl)-N-(2,2,2-trifluoroethyl)valinamide;

N˜2˜-(5-{5-[(1-methylpiperidin-4-yl)methoxy]-1H-pyrrolo[2,3-b]pyridin-3-yl}pyridin-3-yl)-N-(2,2,2-trifluoroethyl)valinamide;

(R)—N,N-dimethyl-3-(5-(3-methyl-1-oxo-1-(2,22-trifluoroethylamino)butan-2-ylamino)pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridine-5-carboxamide;

N-(1-methylethyl)-3-[5-({(1R)-2-methyl-1-[(2,2,2-trifluoroethyl)carbamoyl]propyl}amino)pyridin-3-yl]-1H-pyrrolo[2,3-b]pyridine-5-carboxamide;

N-(2-methoxy-1-methylethyl)-3-[5-({(1R)-2-methyl-1-[(2,2,2-trifluoroethyl)carbamoyl]propyl}amino)pyridin-3-yl]-1H-pyrrolo[2,3-b]pyridine-5-carboxamide;

N-(2-hydroxy-1-methylethyl)-3-[5-({(1R)-2-methyl-1-[(2,2,2-trifluoroethyl)carbamoyl]propyl}amino)pyridin-3-yl]-1H-pyrrolo[2,3-b]pyridine-5-carboxamide;

3-[5-({(1R)-2-methyl-1-[(2,2,2-trifluoroethyl)carbamoyl]propyl}amino)pyridine-3-yl]-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrrolo[2,3-b]pyridine-5-carboxamide;

N˜2˜-{5-[5-(azetidin-1-ylcarbonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridin-3-yl}-N-(2,2,2-trifluoroethyl)-D-valinamide;

N-(2-methylpropyl)-3-[5-({(1R)-2-methyl-1-[(2,2,2-trifluoroethyl)carbamoyl]propyl}amino)pyridin-3-yl]-1H-pyrrolo[2,3-b]pyridine-5-carboxamide;

N-methyl-3-[5-({(1R)-2-methyl-1-[(2,2,2-trifluoroethyl)carbamoyl]propyl}amino) pyridin-3-yl]-1H-pyrrolo[2,3-b]pyridine-5-carboxamide;

N-[(1,1-dioxidotetrahydrothiophen-3-yl)methyl]-3-[5-({(1R)-2-methyl-1-[(2,2,2-trifluoroethyl)carbamoyl]propyl}amino)pyridin-3-yl]-1H-pyrrolo[2,3-b]pyridine-5-carboxamide;

3-[5-({(1R)-2-methyl-1-[(2,2,2-trifluoroethyl)carbamoyl]propyl}amino)pyridin-3-yl]N-(1H-pyrazol-5-ylmethyl)-1H-pyrrolo[2,3-b]pyridine-5-carboxamide;

N-methyl-3-[5-({(1R)-2-methyl-1-[(2,2,2-trifluoroethyl)carbamoyl]propyl}amino) pyridin-3-yl]-N-[1-(1H-pyrazol-5-yl)ethyl]-1H-pyrrolo[2,3-b]pyridine-5-carboxamide;

N-[(1-methyl-1H-pyrazol-4-yl)methyl]-3-[5-({(1R)-2-methyl-1-[(2,2,2-trifluoroethyl)carbamoyl]propyl}amino)pyridin-3-yl]-1H-pyrrolo[2,3-b]pyridine-5-carboxamide;

N˜2˜-(5-{5-[(4-hydroxypiperidin-1-yl)carbonyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}pyridin-3-yl)-N-(2,2,2-trifluoroethyl)-D-valinamide;

N-[(1-hydroxycyclopropyl)methyl]-3-[5-({(1R)-2-methyl-1-[(2,2,2-trifluoroethyl)carbamoyl]propyl}amino)pyridin-3-yl]-1H-pyrrolo[2,3-b]pyridine-5-carboxamide;

3-Methyl-2-(5-(5-sulfamoyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-ylamino)-N-(2,2,2-trifluoroethyl)butanamide;

2-(5-(5-(N,N-dimethylsulfamoyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-ylamino)-3-methyl-N-(2,2,2-trifluoroethyl)butanamide;

N2-[5-(5-amino-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]-N-(2,2-trifluoroethyl)valinamide;

N2-{5-[5-(acetylamino)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridin-3-yl}-N-(2,2,2-trifluoroethyl)valinamide;

N2-(5-{5-[(methylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}pyridin-3-yl)-N-(2,2,2-trifluoroethyl)valinamide;

N2-(5-{5-[(methylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}pyridin-3-yl)-N-(2,2,2-trifluoroethyl)-L-valinamide;

N2-(5-{5-[(methylsulfonyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}pyridin-3-yl)-N-(2,2,2-trifluoroethyl)-D-valinamide;

N2-{5-[5-(propanoylamino)-1H-pyrrolo[2,3-b]pyridin-7-ium-3-yl]pyridin-3-yl}-N-(2,2,2-trifluoroethyl)valinamide;

N˜2˜-(5-{5-[(hydroxyacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}pyridin-3-yl)-N-(2,2,2-trifluoroethyl)valinamide;

N˜2˜-(5-{5-[(methoxyacetyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}pyridin-3-yl)-N-(2,2,2-trifluoroethyl)valinamide;

N2-(5-{5-[(propan-2-ylcarbamoyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}pyridin-3-yl)-N-(2,2,2-trifluoroethyl)valinamide;

N˜2˜-(5-{5-[(propylcarbamoyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}pyridin-3-yl)-N-(2,2,2-trifluoroethyl)valinamide;

N˜2˜-[5-(5-{[(2,4-difluorophenyl)carbamoyl]amino}-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]-N-(2,2,2-trifluoroethyl)valinamide;

N-({3-[5-({2-methyl-1-[(2,2,2-trifluoroethyl)carbamoyl]propyl}amino)pyridin-3-yl]-1H-pyrrolo[2,3-b]pyridin-5-yl}carbamoyl)alanine;

N˜2˜-(5-{5-[(methylcarbamoyl)amino]-1H-pyrrolo[2,3-b]pyridin-3-yl}pyridin-3-yl)-N-(2,2,2-trifluoroethyl)valinamide;

Methyl {3-[5-({3-methyl-1-oxo-1-[(2,2,2-trifluoroethyl)amino]butan-2-yl}amino)pyridin-3-yl]-1H-pyrrolo[2,3-b]pyridin-5-yl}carbamate;

ethyl {3-[5-({2-methyl-1-[(2,2,2-trifluoroethyl)carbamoyl]propyl}amino)pyridin-3yl]-1H-pyrrolo[2,3-b]pyridin-5-yl}carbamate;

1-methylethyl {3-[5-({2-methyl-1-[(2,2,2-trifluoroethyl)carbamoyl]propyl}amino)pyridin-3-yl]-1H-pyrrolo[2,3-b]pyridin-5-yl}carbamate;

N2-{5-[5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridin-3-yl}-N-(2,2,2-trifluoroethyl)valinamide;

N2-{5-[5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridin-3-yl}-N-(2,2,2-trifluoroethyl)-L-valinamide;

N2-{5-[5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridin-3-yl}-N-(2,2,2-trifluoroethyl)-D-valinamide;

(R)-3-methyl-2-(5-(5-((2-(pyrrolidin-1-yl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-ylamino)-N-(2,2,2-trifluoroethyl)butanamide;

N˜2˜-{5-[5-(tert-butoxymethyl)-1H-pyrrolo[2,3-b]pyridine-3-yl]pyridin-3-yl}N-(2,2,2-trifluoroethyl)-D-valinamide;

tert-butyl 4-[2-({3-[5-({(1R)-2-methyl-1-[(2,2,2-trifluoroethyl)carbamoyl]propyl}amino)pyridin-3-yl]-1H-pyrrolo[2,3-b]pyridin-5-yl}methoxy)ethyl]piperazine-1-carboxylate;

N˜2˜-(5-{5-[(2-morpholin-4-ylethoxy)methyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}pyridin-3-yl)-N-(2,2,2-trifluoroethyl)-D-valinamide;

N˜2˜-(5-{5-[(prop-2-en-1-yloxy)methyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}pyridin-3-yl)-N-(2,2,2-trifluoroethyl)-D-valinamide;

tert-butyl 4-({3-[5-({(1R)-2-methyl-1-[(2,2,2-trifluoroethyl)carbamoyl]propyl}amino)pyridin-3-yl]-1H-pyrrolo[2,3-b]pyridin-5-yl}methoxy)piperidine-1-carboxylate;

N˜2˜-{5-[5-(pyrrolidin-1-ylmethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridin-3-yl}-N-(2,2,2-trifluoroethyl)-D-valinamide;

N˜2˜-{3-[5-(methoxymethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-1,2,4-triazin-5-yl}-N-(2,2,2-trifluoroethyl)-D-valinamide;

N˜2˜-{5-[5-(methoxymethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridin-3-yl}-N-(2,2,2-trifluoroethyl)-D-valinamide;

N-((3-(5-(3-methyl-1-oxo-1-(2,2,2-trifluoroethylamino)butan-2-ylamino)pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)methyl)cyclopentanecarboxamide;

N˜2˜-(5-{5-[(propanoylamino)methyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}pyridin-3-yl)-N-(2,2,2-trifluoroethyl)valinamide;

N-({3-[5-({2-methyl-1-[(2,2,2-trifluoroethyl)carbamoyl]propyl}amino)pyridin-3-yl]-1H-pyrrolo[2,3-b]pyridin-5-yl}methyl)cyclohexanecarboxamide;

N˜2˜-[5-(5-{[(2E)-but-2-enoylamino]methyl}-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]-N-(2,2,2-trifluoroethyl)valinamide;

N˜2˜-(5-{5-[(acetylamino)methyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}pyridin-3-yl)-N-(2,2,2-trifluoroethyl)valinamide;

N˜2˜-[5-(5-{[(cyclopropylcarbonyl)amino]methyl}-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]-N-(2,2,2-trifluoroethyl)valinamide;

N˜2˜-{5-[5-({[(4-methyl-1,3-oxazol-5-yl)carbonyl]amino}methyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridin-3-yl}N-(2,2,2-trifluoroethyl)valinamide;

N˜2˜-[5-(5-{[(3-methylbut-2-enoyl)amino]methyl}-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]-N-(2,2,2-trifluoroethyl)valinamide;

N˜2˜-(5-{5-[(butanoylamino)methyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}pyridin-3-yl)-N-(2,2,2-trifluoroethyl)valinamide;

N-(2,2,2-trifluoroethyl)-N˜2˜-[5-(5-{[(3,3,3-trifluoropropanoyl)amino]methyl}-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]valinamide; and

N˜2˜-[5-(5-{[(pyrrolidin-1-ylcarbonyl)amino]methyl}-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl]-N-(2,2,2-trifluoroethyl)valinamide, or a pharmaceutically acceptable salt thereof.

5. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

6. A compound according to claim 1 , wherein R 1 is hydrogen.

Assignments (2)
MERGER Recorded Aug 8, 2022
From: MERCK SHARP & DOHME CORP.
To: MERCK SHARP & DOHME LLC
Reel/Frame 061102/0145 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 24, 2014
From: RIVKIN, ALEXEY; BUTCHER, JOHN W.; WITTER, DAVID; KIM, JUNE; HENDRIX, JOHN; AHEARN, SEAN P.; ACHARYA, RAKSHA; JONES, PHILIP; DINSMORE, CHRISTOPHER; JUNG, JOON
To: MERCK SHARP & DOHME CORP.
Reel/Frame 033381/0125 →