Granted Patent B2

US 8,883,819 · App. 13/599,267 · Granted Nov 11, 2014

Abstract

Claims (152)

1. A compound represented by formula (I)

or a pharmaceutically acceptable salt thereof,

wherein,

A is

R 1 is C 1 -C 4 alkyl; C 1 -C 4 alkoxy optionally substituted by one or more halogen atoms; CN; or halogen;

R 1a is H, halogen, C 1 -C 4 alkyl or C 1 -C 4 haloalkyl;

X is N or CH;

R 2 is H; C 1 -C 8 alkyl optionally substituted by one or more OH, —NR 9 R 11 or C 1 -C 4 alkoxy; C 1 -C 8 haloalkyl; C 2 -C 8 alkynyl substituted by one or more halogen, OH, —NR 9 R 11 or C 1 -C 4 alkoxy; C 3 -C 10 cycloalkyl; —(C 1 -C 4 alkyl)-C 3 -C 8 cycloalkyl; C 1 -C 8 alkoxy optionally substituted by one or more halogen, —NR 9 R 11 or OH; OH; CN; halogen; —(C 0 -C 4 alkyl)-NR 9 R 11 ; —(C 0 -C 4 alkyl)-CO 2 R 15 ; —(C 0 -C 4 alkyl)-C(O)NR 9 R 11 ; —(C 0 -C 4 alkyl)-C 6 -C 14 aryl; or —(C 0 -C 4 alkyl)-3 to 14 membered heterocyclyl; wherein the cycloalkyl, —(C 0 -C 4 alkyl)-C 6 -C 14 aryl and —(C 0 -C 4 alkyl)-3 to 14 membered heterocyclyl are each optionally substituted by one or more Z a substituents;

R 3 is H; C 1 -C 8 alkyl optionally substituted by one or more OH, —NR 9 R 11 or C 1 -C 4 alkoxy; C 1 -C 8 haloalkyl; C 2 -C 8 alkynyl substituted by one or more halogen, OH, —NR 9 R 11 , or C 1 -C 4 alkoxy; C 3 -C 10 cycloalkyl; —(C 1 -C 4 alkyl)-C 3 -C 8 cycloalkyl; C 1 -C 8 alkoxy optionally substituted by one or more halogen, —NR 9 R 11 or OH; OH; CN; halogen; —(C 0 -C 4 alkyl)-NR 9 R 11 ; —(C 0 -C 4 alkyl)-CO 2 R 15 ; —(C 0 -C 4 alkyl)-C(O)NR 9 R 11 ; —(C 0 -C 4 alkyl)-C 6 -C 14 aryl; or —(C 0 -C 4 alkyl)-3 to 14 membered heterocyclyl; wherein the cycloalkyl, —(C 0 -C 4 alkyl)-C 6 -C 14 aryl and —(C 0 -C 4 alkyl)-3 to 14 heterocyclyl are each optionally substituted by one or more Z a substituents;

each Z a is independently OH; (C 0 -C 4 alkyl)-C 6 aryl; O—C 6 aryl; C 1 -C 4 alkyl optionally substituted by one or more OH, CN or —NR 19a R 21a ; C 1 -C 4 haloalkyl; C 1 -C 4 alkoxy optionally substituted by one or more OH, —CO 2 R 19a , —NR 19a R 21a or C 1 -C 4 alkoxy; —NR 18a C(O)R 21a ; —C(O)NR 19a R 21a ; —NR 18a C(O)NR 19a R 21a ; —NR 19a R 21a ; —(C 0 -C 4 alkyl)-C(O)OR 18a ; —(C 0 -C 4 alkyl)-C(O)R 19a ; oxo; CN; NO 2 ; halogen; —(C 0 -C 4 alkyl)-4 to 6 membered heterocyclyl; or —O-(4 to 6 membered heterocyclyl); wherein the (C 0 -C 4 alkyl)-C 6 aryl, O—C 6 aryl, —(C 0 -C 4 alkyl)-4 to 6 membered heterocyclyl and —O-(4 to 6 membered heterocyclyl) are each optionally substituted by OH, halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl or C 1 -C 4 alkoxy optionally substituted by one or more halogens;

R 4 is H;

R 5 is H, C 1 -C 4 alkyl or C 1 -C 4 haloalkyl;

R 6 is selected from C 1 -C 8 alkyl optionally substituted by one or more C 1 -C 4 alkoxy or —NR 19 R 21 ; C 1 -C 8 haloalkyl; —(C 0 -C 4 alkyl)-C 3 -C 8 cycloalkyl; C 1 -C 8 alkoxy optionally substituted by one or more halogen atoms; —NR 19 R 21 ; —(C 0 -C 4 alkyl)-C 6 -C 14 aryl; and —(C 0 -C 4 alkyl)-3 to 14 membered heterocyclyl; wherein the —(C 0 -C 4 alkyl)-C 3 -C 8 cycloalkyl, —(C 0 -C 4 alkyl)-C 6 -C 14 aryl and —(C 0 -C 4 alkyl)-3 to 14 heterocyclyl are each optionally substituted by one or more Z substituents;

each Z is independently selected from (C 0 -C 4 alkyl)-C 6 aryl; O—C 6 aryl; C 1 -C 6 alkyl optionally substituted by one or more C 1 -C 6 alkoxy, CN or —NR 19 R 21 ; C 1 -C 6 haloalkyl; C 1 -C 6 alkoxy optionally substituted by one or more —NR 19 R 21 or C 1 -C 4 alkoxy; —NR 19 R 21 ; (C 0 -C 4 alkyl)-C(O)R 19 ; CN; halogen and (C 0 -C 4 alkyl)-4 to 6 membered heterocyclyl; and wherein the aryl and heterocyclyl are each optionally substituted by one or more halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl and C 1 -C 6 alkoxy optionally substituted by one or more halogens;

R 9 and R 11 are each independently selected from H; C 1 -C 6 alkyl optionally substituted by one or more C 1 -C 4 alkoxy or OH; C 1 -C 6 haloalkyl; —(C 0 -C 1 alkyl)-C 3 -C 6 cycloalkyl; (C 0 -C 4 alkyl)-C 6 -C 14 aryl optionally substituted by one or more groups selected from C 1 -C 6 alkyl, C 1 -C 6 alkoxy and halogen; and (C 0 -C 4 alkyl)-3- to 14-membered heterocyclyl optionally substituted by one or more groups selected from halogen, oxo, C 1 -C 6 alkyl and C(O)C 1 -C 6 alkyl; or

R 9 and R 11 together with the nitrogen atom to which they are attached form a 5- to 10-membered heterocyclyl, which heterocyclyl includes 0 to 3 further heteroatoms selected from N, O and S, the heterocyclyl being optionally substituted by one or more substituents selected from OH; halogen; phenyl, 5- to 10-membered heterocyclyl; C 1 -C 6 alkyl; C 1 -C 6 haloalkyl; C 1 -C 6 alkoxy optionally substituted by one or more OH or C 1 -C 4 alkoxy; and C(O)OC 1 -C 6 alkyl; wherein the phenyl and heterocyclyl substituent groups are themselves optionally substituted by C 1 -C 6 alkyl, C 1 -C 6 haloalkyl or C 1 -C 6 alkoxy;

R 15 is selected from H; C 1 -C 8 alkyl; C 1 -C 8 haloalkyl; C 3 -C 10 cycloalkyl; (—C 1 -C 4 alkyl)-C 3 -C 8 cycloalkyl; —(C 0 -C 4 alkyl)-C 6 -C 14 aryl and —(C 0 -C 4 alkyl)-3 to 14 membered heterocyclyl group; wherein the C 3 -C 10 cycloalkyl, (—C 1 -C 4 alkyl)-C 3 -C 8 cycloalkyl, —(C 0 -C 4 alkyl)-C 6 -C 14 aryl and —(C 0 -C 4 alkyl)-3 to 14 membered heterocyclyl groups are each optionally substituted by one or more Z substituents;

R 18a is independently H or C 1 -C 6 alkyl;

R 19a and R 21a are each independently H; C 1 -C 6 alkyl optionally substituted by one or more C 1 -C 4 alkoxy, —NR 22 R 23 , or OH; C 1 -C 6 haloalkyl; —(C 0 -C 1 alkyl)-C 3 -C 6 cycloalkyl; —(C 0 -C 4 alkyl)-C 6 -C 14 aryl optionally substituted by one or more groups selected from C 1 -C 6 alkyl, C 1 -C 6 alkoxy and halogen; or —(C 0 -C 4 alkyl)-3- to 14-membered heterocyclyl optionally substituted by one or more groups selected from halogen, oxo, C 1 -C 6 alkyl and C(O)C 1 -C 6 alkyl; or

R 19a and R 21a together with the nitrogen atom to which they attached form a 5- to 10-membered heterocyclyl, which heterocyclyl includes 0 to 3 further heteroatoms selected from N, O and S, the heterocyclyl being optionally substituted by one or more substituents selected from OH; halogen; phenyl; 5- to 10-membered heterocyclyl; C 1 -C 6 alkyl; C 1 -C 6 haloalkyl; C 1 -C 6 alkoxy optionally substituted by one or more OH or C 1 -C 4 alkoxy; and C(O)OC 1 -C 6 alkyl; wherein the phenyl and heterocyclyl substituent groups are themselves optionally substituted by C 1 -C 6 alkyl, C 1 -C 6 haloalkyl or C 1 -C 6 alkoxy;

R 18 is independently H or C 1 -C 6 alkyl;

R 19 and R 21 are each independently C 1 -C 6 alkyl optionally substituted by one or more C 1 -C 4 alkoxy; C 1 -C 6 haloalkyl; —(C 0 -C 1 alkyl)-C 3 -C 6 cycloalkyl; —(C 0 -C 4 alkyl)-C 6 -C 14 aryl optionally substituted by one or more groups selected from C 1 -C 6 alkyl, C 1 -C 6 alkoxy and halogen; or —(C 0 -C 4 alkyl)-3- to 14-membered heterocyclyl, optionally substituted by one or more groups selected from halogen, C 1 -C 6 alkyl and —C(O)C 1 -C 6 alkyl; or

R 19 and R 21 together with the nitrogen atom to which they attached form a 5- to 10-membered heterocyclyl, which heterocyclyl includes 0 to 3 further heteroatoms selected from N, O and S, the heterocyclyl being optionally substituted by one or more substituents selected from halogen; phenyl; 5- to 10-membered heterocyclyl; C 1 -C 6 alkyl; C 1 -C 6 haloalkyl; C 1 -C 6 alkoxy optionally substituted by one or more C 1 -C 4 alkoxy and C(O)OC 1 -C 6 alkyl; wherein the phenyl and heterocyclyl substituent groups are themselves optionally substituted by a substituent selected from C 1 -C 6 alkyl, C 1 -C 6 haloalkyl and C 1 -C 6 alkoxy; and

R 22 and R 23 are each independently H or C 1 -C 6 alkyl.

2. The compound according to claim 1 , wherein

R 5 is H;

R 6 is C 1 -C 4 alkyl optionally substituted by one or more C 1 -C 4 alkoxy; phenyl; C 1 -C 4 haloalkyl; tetrahydrofuran; pyrrolidine, —CH 2 -pyrrolidine or —CH 2 -piperidine; wherein phenyl, tetrahydrofuran, pyrrolidine, —CH 2 -pyrrolidine and —CH 2 -piperidine are each optionally substituted by one or more Z substituents; and

each Z is independently C 1 -C 4 alkoxy, halogen, C 1 -C 4 alkyl or C 1 -C 4 haloalkyl.

3. The compound according to claim 1 , wherein

R 2 is H; C 1 -C 8 alkyl optionally substituted by one or more OH, —NR 9 R 11 or C 1 -C 4 alkoxy; C 1 -C 8 haloalkyl; C 2 -C 8 alkynyl substituted by one or more halogen, OH, —NR 9 R 11 or C 1 -C 4 alkoxy; C 3 -C 10 cycloalkyl; —(C 1 -C 4 alkyl)-C 3 -C 8 cycloalkyl; C 1 -C 8 alkoxy optionally substituted by one or more halogen, —NR 9 R 11 or OH; OH; CN; halogen; —(C 0 -C 4 alkyl)-NR 9 R 11 ; —(C 0 -C 4 alkyl)-CO 2 R 15 ; —(C 0 -C 4 alkyl)-C(O)NR 9 R 11 ; —(C 0 -C 4 alkyl)-C 6 -C 14 aryl; or —(C 0 -C 4 alkyl)-3 to 14 membered heterocyclyl; wherein the cycloalkyl, —(C 0 -C 4 alkyl)-C 6 -C 14 aryl and —(C 0 -C 4 alkyl)-3 to 14 membered heterocyclyl are each optionally substituted by one or more Z a substituents;

R 3 is H;

R 9 and R 11 are each independently H; C 1 -C 6 alkyl optionally substituted by one or more C 1 -C 4 alkoxy or OH; C 1 -C 6 haloalkyl; —(C 0 -C 1 alkyl)-C 3 -C 6 cycloalkyl; (C 0 -C 4 alkyl)-C 6 -C 14 aryl optionally substituted by one or more groups selected from C 1 -C 6 alkyl, C 1 -C 6 alkoxy and halogen; or (C 0 -C 4 alkyl)-5- to 6-membered heterocyclyl optionally substituted by one or more groups selected from halogen, oxo, C 1 -C 6 alkyl and C(O)C 1 -C 6 alkyl;

Z a is independently OH; (C 0 -C 4 alkyl)-C 6 aryl; O—C 6 aryl; C 1 -C 4 alkyl optionally substituted by one or more OH, CN or —NR 19a R 21a ; C 1 -C 4 haloalkyl; C 1 -C 4 alkoxy optionally substituted by one or more OH, —CO 2 R 19a , —NR 9a R 21a or C 1 -C 4 alkoxy; —NR 18a C(O)R 21a ; —C(O)NR 19a R 21a ; —NR 18a C(O)NR 19a R 21a ; —NR 19a R 21a ; (C 0 -C 4 alkyl)-C(O)OR 18a ; (C 0 -C 4 alkyl)-C(O)R 19a ; oxo; CN; NO 2 ; halogen; or (C 0 -C 4 alkyl)-4 to 6 membered heterocyclyl; wherein the aryl and heterocyclyl are each optionally substituted by halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl or C 1 -C 4 alkoxy optionally substituted by one or more halogens;

R 18a is independently H or C 1 -C 6 alkyl;

R 19a and R 21a are each independently H; C 1 -C 6 alkyl optionally substituted by one or more C 1 -C 4 alkoxy or OH; C 1 -C 6 haloalkyl; —(C 0 -C 1 alkyl)-C 3 -C 6 cycloalkyl; —(C 0 -C 4 alkyl)-C 6 -C 14 optionally substituted by one or more groups selected from C 1 -C 6 alkyl, C 1 -C 6 alkoxy and halogen; or (C 0 -C 4 alkyl)-5- to 6-membered heterocyclyl optionally substituted by one or more groups selected from halogen, oxo, C 1 -C 6 alkyl and C(O)C 1 -C 6 alkyl; or

R 19a and R 21a together with the nitrogen atom to which they attached form a 5- to 10-membered heterocyclyl, which heterocyclyl includes 0 to 3 further heteroatoms selected from N, O and S, the heterocyclyl being optionally substituted by one or more substituents selected from OH; halogen; phenyl; 5- to 10-membered heterocyclyl; C 1 -C 6 alkyl; C 1 -C 6 haloalkyl; C 1 -C 6 alkoxy optionally substituted by one or more OH or C 1 -C 4 alkoxy; or C(O)OC 1 -C 6 alkyl; wherein the phenyl and heterocyclyl substituent groups are themselves optionally substituted by C 1 -C 6 alkyl, C 1 -C 6 haloalkyl or C 1 -C 6 alkoxy.

4. The compound according to claim 1 , wherein

R 2 is H; C 1 -C 4 alkyl optionally substituted by one or more OH or —NR 9 R 11 ; C 1 -C 4 haloalkyl; C 1 -C 4 alkoxy optionally substituted by one or more halogen, —NR 9 R 11 or OH; OH; CN; halogen; —(C 0 -C 4 alkyl)-NR 9 R 11 ; —(C 0 -C 4 alkyl)-C(O)NR 9 R 11 ; phenyl; or —(C 0 -C 4 alkyl)-5 to 6 membered heterocyclyl; wherein the phenyl and —(C 0 -C 4 alkyl)-5 to 6 membered heterocyclyl are each optionally substituted by one or more Z a substituents;

R 3 is H;

R 9 and R 11 are each independently H; C 1 -C 6 alkyl optionally substituted by one or more C 1 -C 4 alkoxy or OH; C 1 -C 6 haloalkyl; —(C 0 -C 1 alkyl)-C 3 -C 6 cycloalkyl; (C 0 -C 4 alkyl)-C 6 -C 14 optionally substituted by one or more groups selected from C 1 -C 6 alkyl, C 1 -C 6 alkoxy and halogen; or (C 0 -C 4 alkyl)-5- to 6-membered heterocyclyl optionally substituted by one or more groups selected from halogen, oxo, C 1 -C 6 alkyl and C(O)C 1 -C 6 alkyl;

each Z a is independently OH; C 1 -C 4 alkyl optionally substituted by one or more OH or —NR 19a R 21a ; C 1 -C 4 haloalkyl; C 1 -C 4 alkoxy optionally substituted by one or more OH, C 1 -C 4 alkoxy or —NR 19a R 21a ; —C(O)NR 19a R 21a ; CN; halogen or —(C 0 -C 4 alkyl)-4 to 6 membered heterocyclyl; wherein the heterocyclyl is optionally substituted by halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl or C 1 -C 4 alkoxy optionally substituted by one or more halogens;

R 19a and R 21a are each independently H; C 1 -C 4 alkyl optionally substituted by one or more C 1 -C 4 alkoxy or OH; C 1 -C 4 haloalkyl; —(C 0 -C 1 alkyl)-C 3 -C 6 cycloalkyl; —(C 0 -C 4 alkyl)-C 6 -C 14 optionally substituted by one or more groups selected from C 1 -C 6 alkyl, C 1 -C 6 alkoxy and halogen; or —(C 0 -C 4 alkyl)-5- to 6-membered heterocyclyl optionally substituted by one or more groups selected from halogen, oxo, C 1 -C 6 alkyl and C(O)C 1 -C 6 alkyl.

5. The compound according to claim 1 , wherein

R 1 is fluorine or methyl;

R 1a is H;

6. The compound according to claim 1 , which is selected from:

N-(2-Fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)-7-(1-methyl-1H-pyrazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide;

7-(3-Fluoro-4-(2-hydroxyethylcarbamoyl)phenyl)-N-(2-fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;

7-Bromo-N-(2-methyl-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;

7-(1-Methyl-1H-pyrazol-5-yl)-N-(2-methyl-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(2-Fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)-7-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(2-Fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-(3,4-difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(1-methyl-1H-pyrazol-5-yl) imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-(benzylcarbamoyl)-2-fluorophenyl)-6-(1-methyl-1H-pyrazol-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(4-fluoro-2-methyl-5-(2-(4-methyl piperazin-1-yl)benzylcarbamoyl)phenyl)-7-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-(3,4-difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(6-(3-(dimethylamino) propoxy)pyridine-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-(2-(2,6-cis-dimethylpiperidin-1-yl)ethylcarbamoyl)-2-fluorophenyl)-7-(1-methyl-1H-pyrazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide;

7-(4-(aminomethyl)phenyl)-N-(2-fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-(2-tert-butoxyethylcarbamoyl)-2-fluorophenyl)-7-(1-(2-morpholinoethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-((5,5-dimethyltetrahydrofuran-2-yl)methyl carbamoyl)-2-fluorophenyl)-7-(1-(2-morpholinoethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(2-fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)-7-(6-methoxy pyridine-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(2-fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)-6-(1-methyl-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyridine-3-carboxamide;

1-(2-(4-fluoro-3-(7-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-carboxamido)benzamido)ethyl)-2,6-cis-dimethylpiperidine;

N-(5-(2-tert-butoxyethylcarbamoyl)-2-fluorophenyl)-6-(6-(3-(dimethylamino)propoxy)pyridine-3-yl)pyrazolo[1,5-a]pyridine-3-carboxamide;

N-(2-methyl-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)-7-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;

1-methyl-4-(2-((6-methyl-5-(7-(1-methyl-1H-pyrazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamido)nicotinamido)methyl)phenyl)piperazin-1H-ium;

7-(1-Methyl-1H-pyrazol-4-yl)-imidazo[1,2-a]pyridine-3-carboxylic acid {5-[2-(2,6-cis-dimethyl-piperidin-1-yl)-ethylcarbamoyl]-2-fluoro-phenyl)}-amide;

N-(5-(2-tert-Butoxyethylcarbamoyl)-2-fluorophenyl)-7-(6-(3-(dimethylamino)propoxy)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(6-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;

6-(1-Methyl-1H-pyrazol-5-yl)-N-(2-methyl-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide;

N-(2-Bromo-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(2-Bromo-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide;

N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(3-hydroxy-3-methyl butyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(3-fluoro-4-(2-(piperidin-1-yl)ethylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(3-fluoro-4-(2-(tetrahydro-2H-pyran-4-yl)ethylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(3-fluoro-4-(3-morpholino propylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-((5,5-Dimethyltetrahydrofuran-2-yl)methylcarbamoyl)-2-fluorophenyl)-7-(5-((tetrahydro-2H-pyran-4-ylamino)methyl)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;

(S)—N-(5-(((5,5-Dimethyltetrahydrofuran-2-yl)methyl)carbamoyl)-2-fluorophenyl)-7-(5-(((2-fluoroethyl)amino)methyl)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;

(R)—N-(5-(((5,5-dimethyltetrahydrofuran-2-yl)methyl)carbamoyl)-2-fluorophenyl)-7-(5-(((2-methoxyethyl)(methyl)amino)methyl)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;

(R)-7-(5-((tert-butylamino)methyl)pyridin-3-yl)-N-(5-(((5,5-dimethyltetrahydrofuran-2-yl)methyl)carbamoyl)-2-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(6-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-((2-(tert-Butoxy)ethyl)carbamoyl)-2-fluoro phenyl)-7-(6-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-(((5,5-dimethyl tetrahydrofuran-2-yl)methyl)carbamoyl)-2-fluorophenyl)-7-(6-((1-methyl piperidin-4-yl)oxy)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;

6-(1-Methyl-1H-pyrazol-5-yl)-N-(2-methyl-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide;

N-(2-Bromo-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(2-Bromo-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide;

N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(3-hydroxy-3-methyl butyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(3-fluoro-4-(2-(piperidin-1-yl)ethylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(3-fluoro-4-(2-(tetrahydro-2H-pyran-4-yl)ethylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-((2-(2,2-Dimethylpyrrolidin-1-yl)ethyl)carbamoyl)-2-fluorophenyl)-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-(2-(2,2-Dimethylpyrrolidin-1-yl)ethylcarbamoyl)-2-fluorophenyl)-7-(3-fluoro-4-(1-hydroxy-2-methylpropan-2-ylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-(2-(2,2-Dimethylpyrrolidin-1-yl)ethylcarbamoyl)-2-methylpyridin-3-yl)-6-(3-fluoro-4-(1-hydroxy-2-methylpropan-2-ylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide;

N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(3-fluoro-4-(3-morpholino propylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-(2-(2,6-cis-Dimethylpiperidin-1-yl)ethylcarbamoyl)-2-fluorophenyl)-7-(3-fluoro-4-(1-hydroxy-2-methylpropan-2-ylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;

7-(3-Fluoro-4-(2-fluoroethylcarbamoyl)phenyl)-N-(2-fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(2-Fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)-7-(3-fluoro-5-(2-hydroxy ethylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-(2-(2,2-dimethylpyrrolidin-1-yl)ethylcarbamoyl)-2-methylpyridin-3-yl)-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide;

(S)—N-(2-Fluoro-5-(2-(2-(methoxy methyl)pyrrolidin-1-yl)ethyl carbamoyl)phenyl)-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(2-Fluoro-5-((2-(3-propylpyrrolidin-1-yl)ethyl)carbamoyl)phenyl)-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide;

(R)—N-(2-Fluoro-5-((2-(2-(methoxymethyl)pyrrolidin-1-yl)ethyl)carbamoyl)phenyl)-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-((2-(3,5-Dimethylpiperidin-1-yl)ethyl)carbamoyl)-2-fluorophenyl)-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(2-fluoro-5-((2-(2,2,6,6-tetra methylpiperidin-1-yl)ethyl)carbamoyl)phenyl)-7-(1-methyl-1H-pyrazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-((2-(2,2-dimethylpyrrolidin-1-yl)ethyl)carbamoyl)-2-methylpyridin-3-yl)-6-(1-methyl-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyridine-3-carboxamide;

N-(5-((2-(butyl(ethyl)amino)ethyl)carbamoyl)-2-fluoro phenyl)-7-(3-fluoro-4-((2-hydroxy ethyl)carbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;

7-(3-fluoro-4-((1-hydroxy-2-methylpropan-2-yl)carbamoyl)phenyl)-N-(2-fluoro-5-((2-(3-propylpyrrolidin-1-yl)ethyl)carbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-((2-(3,3-dimethylmorpholino)ethyl)carbamoyl)-2-fluorophenyl)-7-(3-fluoro-4-((1-hydroxy-2-methylpropan-2-yl)carbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;

(R)-7-(3-fluoro-4-((1-hydroxy-2-methylpropan-2-yl)carbamoyl)phenyl)-N-(2-fluoro-5-((2-(2-(methoxymethyl)pyrrolidin-1-yl)ethyl)carbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-((3,4-Difluorobenzyl)carbamoyl)-2-fluorophenyl)-7-(6-((2-(dimethylamino)ethyl)carbamoyl)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-((2-(2,2-Dimethylpiperidin-1-yl)ethyl)carbamoyl)-2-methylpyridin-3-yl)-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide;

N-(5-((2-(2,6-cis-Dimethylpiperidin-1-yl)ethyl)carbamoyl)-2-methylpyridin-3-yl)-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide;

N-(5-((2-((2S,3R)-2,3-diethylazetidin-1-yl)ethyl)carbamoyl)-2-fluorophenyl)-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(6-(((2-hydroxyethyl)(methyl)amino)methyl)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-((3,4-difluorobenzyl)carbamoyl)-2-fluorophenyl)-7-(6-((methyl(phenethyl)amino)methyl)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-((3,4-Difluoro benzyl)carbamoyl)-2-fluorophenyl)-7-(5-((methylamino)methyl)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;

7-(5-((Cyclohexyl amino)methyl)pyridin-3-yl)-N-(5-((3,4-difluorobenzyl)carbamoyl)-2-fluoro phenyl)imidazo[1,2-a]pyridine-3-carboxamide; and

N-(5-((3,4-Difluoro benzyl)carbamoyl)-2-fluorophenyl)-7-(5-(((2-methoxyethyl)(methyl)amino)methyl)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;

or a pharmaceutically acceptable salt thereof.

7. The compound of claim 1 , wherein X is N.

8. The compound of claim 7 , wherein R 2 is phenyl or 5- or 6-membered heterocyclyl, each optionally substituted by one, two or three Z a substituents.

9. The compound of claim 8 , wherein R 6 is —(C 0 -C 2 alkyl)-5 to 6 membered heterocyclyl, optionally substituted by one, two or three Z substituents.

10. The compound of claim 9 , wherein each Z is independently C 1 -C 4 alkoxy, halogen, C 1 -C 4 alkyl or C 1 -C 4 haloalkyl.

11. The compound of claim 1 , which is

N-(5-((2-(2,2-Dimethylpyrrolidin-1-yl)ethyl)carbamoyl)-2-fluorophenyl)-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide or a pharmaceutically acceptable salt thereof.

12. The compound of claim 1 , which is

N-(5-(2-(2,6-cis-Dimethylpiperidin-1-yl)ethylcarbamoyl)-2-fluorophenyl)-7-(1-methyl-1H-pyrazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide or a pharmaceutically acceptable salt thereof.

13. The compound of claim 1 , which is

N-(5-(2-(2,2-dimethylpyrrolidin-1-yl)ethylcarbamoyl)-2-methylpyridin-3-yl)-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide or a pharmaceutically acceptable salt thereof.

14. The compound of claim 1 , which is

7-(1-Methyl-1H-pyrazol-4-yl)-imidazo[1,2-a]pyridine-3-carboxylic acid {5-[2-(2,6-cis-dimethyl-piperidin-1-yl)-ethylcarbamoyl]-2-fluoro-phenyl}-amide or a pharmaceutically acceptable salt thereof.

15. The compound of claim 1 , which is

N-(5-((2-(2,2-dimethylpyrrolidin-1-yl)ethyl)carbamoyl)-2-methylpyridin-3-yl)-6-(1-methyl-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyridine-3-carboxamide or a pharmaceutically acceptable salt thereof.

16. The compound of claim 1 , which is

N-(5-(2-(2,6-cis-Dimethylpiperidin-1-yl)ethylcarbamoyl)-2-fluorophenyl)-7-(3-fluoro-4-(1-hydroxy-2-methylpropan-2-ylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide or a pharmaceutically acceptable salt thereof.

17. A pharmaceutical composition, comprising a therapeutically effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers.

18. A pharmaceutical combination, comprising a therapeutically effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a second active agent.

19. The pharmaceutical composition of claim 17 , wherein the compound is selected from:

N-(5-((2-(2,2-Dimethylpyrrolidin-1-yl)ethyl)carbamoyl)-2-fluorophenyl)-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-(2-(2,6-cis-Dimethylpiperidin-1-yl)ethylcarbamoyl)-2-fluorophenyl)-7-(1-methyl-1H-pyrazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-(2-(2,2-dimethylpyrrolidin-1-yl)ethylcarbamoyl)-2-methylpyridin-3-yl)-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide;

7-(1-Methyl-1H-pyrazol-4-yl)-imidazo[1,2-a]pyridine-3-carboxylic acid {5-[2-(2,6-cis-dimethyl-piperidin-1-yl)-ethylcarbamoyl]-2-fluoro-phenyl}-amide;

N-(5-((2-(2,2-dimethylpyrrolidin-1-yl)ethyl)carbamoyl)-2-methylpyridin-3-yl)-6-(1-methyl-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyridine-3-carboxamide; and

N-(5-(2-(2,6-cis-Dimethylpiperidin-1-yl)ethylcarbamoyl)-2-fluorophenyl)-7-(3-fluoro-4-(1-hydroxy-2-methylpropan-2-ylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;

or a pharmaceutically acceptable salt thereof.

20. The pharmaceutical combination of claim 18 , wherein the compound is selected from:

N-(5-((2-(2,2-Dimethylpyrrolidin-1-yl)ethyl)carbamoyl)-2-fluorphenyl)-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-(2-(2,6-cis-Dimethylpiperidin-1-yl)ethylcarbamoyl)-2-fluorophenyl)-7-(1-methyl-1H-pyrazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-(2-(2,2-dimethylpyrrolidin-1-yl)ethylcarbamoyl)-2-methylpyridin-3-yl)-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide;

7-(1-Methyl-1H-pyrazol-4-yl)-imidazo[1,2-a]pyridine-3-carboxylic acid {5-[2-(2,6-cis-dimethyl-piperidin-1-yl)-ethylcarbamoyl]-2-fluoro-phenyl}-amide;

N-(5-((2-(2,2-dimethylpyrrolidin-1-yl)ethyl)carbamoyl)-2-methylpyridin-3-yl)-6-(1-methyl-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyridine-3-carboxamide; and

N-(5-(2-(2,6-cis-Dimethylpiperidin-1-yl)ethylcarbamoyl)-2-fluorophenyl)-7-(3-fluoro-4-(1-hydroxy-2-methylpropan-2-ylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;

or a pharmaceutically acceptable salt thereof.

Assignments (12)