Imidazopyridines Syk inhibitors

1. A compound of Formula (I):

wherein

R 1 is selected from pyridinyl, pyrimidinyl, pyridazinyl, pyrazolyl, and thiazolyl, each of which is optionally substituted, and each of which is further optionally fused to a heterocyclic or heteroaryl group, each of which is optionally substituted,

R 2 is selected from 2,3-dimethyl-2H-indazol-6-yl, 1-methyl-1H-indazol-5-yl, 3,4-dihydro-2H-1,4-benzoxazin-3-one-6-yl, 1-(2-hydroxyethyl)-1H-benzo[d]imidazol-2(3H)-one-5-yl, 3-amino-1H-indazol-6-yl, 1H-pyrrolo[3,2-b]pyridine-6-yl, 1,3-benzoxazol-6-yl, 3,4-dihydro-2H-1,4-benzoxazin-6-yl, 2-hydroxyquinoxalin-7-yl, 3-aminoquinolin-6-yl, 2,3-dihydro-1H-indol-6-yl, 1H,2H,3H-pyrido[2,3-b][1,4]oxazin-2-one, (3-hydroxyethyl)-1H-indol-6-yl, benzothiazolyl, 2-aminoquinazolin-6-yl, 3,3-dimethylindolin-2-one, 2,3-dihydro-1H-indol-2-one, 4-fluoro-1H-indazol-6-yl, 5-fluoro-1H-indazol-6-yl, and 3-amino-1H-indazol-6-yl; and

R 3 is hydrogen or lower alkyl, provided that if R 1 is 5-(morpholine-4-carbonyl)-pyridin-2-yl, then R 3 is lower alkyl,

or a pharmaceutically acceptable salt, solvate, or solvate of the salt thereof.

2. The compound of claim 1 or a pharmaceutically acceptable salt, solvate, or solvate of the salt thereof, wherein R 1 is selected from pyridinyl, pyrimidinyl, pyridazinyl, pyrazolyl, and thiazolyl, each of which is optionally substituted with one or more groups selected from

hydroxy;

—NR b R c wherein R b is selected from hydrogen and C 1 -C 6 alkyl optionally substituted with one or two groups selected from hydroxy and —OC 1 -C 4 alkyl and R c is independently selected from hydrogen and C 1 -C 4 alkyl optionally substituted with one or two groups selected from hydroxy and —OC 1 -C 4 alkyl;

heterocycloalkyl optionally substituted with one or two groups selected from hydroxy, C 3 -C 6 cycloalkyl, C 1 -C 4 alkyl, —C 1 -C 4 alkyl-OH, —C 1 -C 4 alkyl-O—C 1 -C 4 alkyl, —C 1 -C 4 alkyl-NH 2 , —N(C 1 -C 4 alkyl)(C 1 -C 4 alkyl), —NH(C 1 -C 4 alkyl), —C(O)(C 1 -C 4 alkyl), —C(O)(C 1 -C 4 alkyl-OH), and —OC 1 -C 4 alkyl;

—OC 1 -C 6 alkyl optionally substituted with one or two groups selected from hydroxy, C 3 -C 6 cycloalkyl, C 1 -C 4 alkyl, —C 1 -C 4 alkyl-OH, —C 1 -C 4 alkyl-O—C 1 -C 4 alkyl, —C 1 -C 4 alkyl-NH 2 , —N(C 1 -C 4 alkyl)(C 1 -C 4 alkyl), —NH(C 1 -C 4 alkyl), and —OC 1 -C 4 alkyl; and

C 1 -C 6 alkyl optionally substituted with one or two groups selected from hydroxy, C 3 -C 6 cycloalkyl, C 1 -C 4 alkyl, —C 1 -C 4 alkyl-OH, —C 1 -C 4 alkyl-O—C 1 -C 4 alkyl, —C 1 -C 4 alkyl-NH 2 , —N(C 1 -C 4 alkyl)(C 1 -C 4 alkyl), —NH(C 1 -C 4 alkyl), and —OC 1 -C 4 alkyl.

3. The compound of claim 1 or a pharmaceutically acceptable salt, solvate, or solvate of the salt thereof, wherein R 1 is selected from pyridinyl, pyrimidinyl, pyridazinyl, pyrazolyl, and thiazolyl, each of which is optionally substituted with one or more groups selected from:

hydroxy;

—NR b R c wherein R b is selected from hydrogen and C 1 -C 6 alkyl optionally substituted with one or two groups selected from hydroxy and —OC 1 -C 4 alkyl and R c is independently selected from hydrogen and C 1 -C 4 alkyl optionally substituted with one or two groups selected from hydroxy and —OC 1 -C 4 alkyl;

heterocycloalkyl optionally substituted with one or two groups selected from hydroxy, —OC 1 -C 4 alkyl, —C 1 -C 4 alkyl-OH, and C 1 -C 4 alkyl;

—OC 1 -C 6 alkyl optionally substituted with one or two groups selected from hydroxy, —OC 1 -C 4 alkyl, —NH 2 , —N(C 1 -C 4 alkyl)H, and —N(C 1 -C 4 alkyl)(C 1 -C 4 alkyl); and

C 1 -C 6 alkyl optionally substituted with hydroxy.

4. The compound of claim 1 or a pharmaceutically acceptable salt, solvate, or solvate of the salt thereof, wherein R 1 is selected from

5,6-dimethoxypyridin-2-yl,

5-(morpholin-4-yl)pyridin-2-yl,

(R)-5-(2-(hydroxymethyl)morpholino)pyridin-2-yl,

(S)-5-(2-(hydroxymethyl)morpholino)pyridin-2-yl,

6-aminopyridin-2-yl,

5-(4-hydroxy-4-methylpiperidin-1-yl)pyridin-2-yl,

5-((2-hydroxyethyl)(methyl)amino)pyridin-2-yl,

5-((2-methoxyethyl)(methyl)amino)pyridin-2-yl,

5-(3-hydroxyazetidin-1-yl)pyridin-2-yl,

5-(3-hydroxy-3-methylazetidin-1-yl)pyridin-2-yl,

5-(2-hydroxy-2-methylpropoxy)pyridin-2-yl,

5-(ethyl(2-hydroxyethyl)amino)pyridin-2-yl,

5-(4-acetylpiperazin-1-yl)pyridin-2-yl,

5-(4-(2-hydroxyacetyl)piperazin-1-yl)pyridin-2-yl,

5-(4-ethylpiperazin-1-yl)pyridin-2-yl,

pyrimidin-4-yl,

2-methoxypyrimidin-4-yl,

1-methyl-1H-pyrazol-3-yl,

1-ethyl-1H-pyrazol-3-yl,

1-ethyl-5-methyl-1H-pyrazol-3-yl,

1,5-dimethyl-1H-pyrazol-3-yl,

1-(2-hydroxyethyl)-5-methyl-1H-pyrazol-3-yl,

5-(hydroxymethyl)-1-methyl-1H-pyrazol-3-yl,

6-(morpholin-4-yl)pyridazin-3-yl, and

2-morpholinothiazol-4-yl.

5. The compound of claim 1 or a pharmaceutically acceptable salt, solvate, or solvate of the salt thereof, wherein R 1 is selected from pyridinyl, pyrimidinyl, pyridazinyl, pyrazolyl, and thiazolyl, each of which is optionally substituted and each of which is fused to a heterocyclic or heteroaryl group, each of which is optionally substituted.

6. The compound of claim 1 or a pharmaceutically acceptable salt, solvate, or solvate of the salt thereof, wherein R 1 is optionally substituted pyrazolyl fused to a heterocyclic or heteroaryl group, which is optionally substituted.

7. The compound of claim 1 or a pharmaceutically acceptable salt, solvate, or solvate of the salt thereof, wherein R 1 is selected from

6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-yl,

5-acetyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl, and

5-methanesulfonyl-4H,5H,6H,7H-pyrazolo[1,5-a]pyrazin-2-yl.

8. The compound of claim 1 or a pharmaceutically acceptable salt, solvate, or solvate of the salt thereof, wherein R 3 is selected from hydrogen and methyl.

9. The compound of claim 1 or a pharmaceutically acceptable salt, solvate, or solvate of the salt thereof, wherein R 2 is selected from 1-methyl-1H-indazol-5-yl, 3,4-dihydro-2H-1,4-benzoxazin-3-one-6-yl, 1H-pyrrolo[3,2-b]pyridine-6-yl, and 3-aminoquinolin-6-yl.

10. A compound selected from the group consisting of:

N-[6-(1H-indazol-6-yl)imidazo[1,2-a]pyridin-8-yl]-5,6-dimethoxypyridin-2-amine,

N-[6-(1H-indazol-6-yl)imidazo[1,2-a]pyridin-8-yl]pyrimidin-4-amine,

N-[6-(1,3-benzothiazol-5-yl)imidazo[1,2-a]pyridin-8-yl]-5,6-dimethoxypyridin-2-amine,

7-{8-[(5,6-dimethoxypyridin-2-yl)amino]imidazo[1,2-a]pyridin-6-yl}quinoxalin-2-ol,

6-{8-[(5,6-dimethoxypyridin-2-yl)amino]imidazo[1,2-a]pyridin-6-yl}-1H-indazol-3-amine,

N-[6-(3,4-dihydro-2H-1,4-benzoxazin-6-yl)imidazo[1,2-a]pyridin-8-yl]-5,6-dimethoxypyridin-2-amine,

N-[6-(1H-indazol-6-yl)imidazo[1,2-a]pyridin-8-yl]-1,5-dimethyl-1H-pyrazol-3-amine,

6-{8-[(1-ethyl-1H-pyrazol-3-yl)amino]imidazo[1,2-a]pyridin-6-yl}-3,4-dihydro-2H-1,4-benzoxazin-3-one,

6-{8-[(1-ethyl-1H-pyrazol-3-yl)amino]imidazo[1,2-a]pyridin-6-yl}quinazolin-2-amine,

1,5-dimethyl-N-[6-(1-methyl-1H-1,3-benzodiazol-6-yl)imidazo[1,2-a]pyridin-8-yl]-1H-pyrazol-3-amine,

N-[6-(1H-indazol-6-yl)imidazo[1,2-a]pyridin-8-yl]-2-methoxypyrimidin-4-amine,

N-[6-(3,4-dihydro-2H-1,4-benzoxazin-6-yl)imidazo[1,2-a]pyridin-8-yl]-1,5-dimethyl-1H-pyrazol-3-amine,

N-[6-(1H-indazol-6-yl)imidazo[1,2-a]pyridin-8-yl]-1-methyl-1H-pyrazol-3-amine,

1,5-dimethyl-N-[6-(1-methyl-1H-1,3-benzodiazol-5-yl)imidazo[1,2-a]pyridin-8-yl]-1H-pyrazol-3-amine,

2-N-[6-(1H-indazol-6-yl)imidazo[1,2-a]pyridin-8-yl]pyridine-2,6-diamine,

1-(6-{[6-(1H-indazol-6-yl]imidazo[1,2-a]pyridin-8-yl]amino}pyridin-3-yl)-4-methylpiperidin-4-ol,

6-(1H-indazol-6-yl)-N-{4H,6H,7H-pyrazolo[3,2-c][1,4]oxazin-2-yl}imidazo[1,2-a]pyridin-8-amine,

6-(8-{[6-(morpholin-4-yl)pyridazin-3-yl]amino}imidazo[1,2-a]pyridin-6-yl)-3,4-dihydro-2H-1,4-benzoxazin-3-one;

[(2S)-4-(6-{[6-(1H-indazol-6-yl)imidazo[1,2-a]pyridin-8-yl]amino}pyridin-3-yl)morpholin-2-yl]methanol;

[(2R)-4-(6-{[6-(1H-indazol-6-yl)imidazo[1,2-a]pyridin-8-yl]amino}pyridin-3-yl)morpholin-2-yl]methanol;

N-[6-(1H-indazol-6-yl)imidazo[1,2-a]pyridin-8-yl]-2-(morpholin-4-yl)-1,3-thiazol-4-amine;

N-{4H,6H,7H-pyrazolo[3,2-c][1,4]oxazin-2-yl}-6-{1H-pyrrolo[3,2-b]pyridin-6-yl}imidazo[1,2-a]pyridin-8-amine;

1-methyl-N-(6-{1H-pyrrolo[3,2-b]pyridin-6-yl}imidazo[ 1,2-a]pyridin-8-yl)-1H-pyrazol-3-amine;

N-(5-methyl-6-{1H-pyrrolo[3,2-b]pyridin-6-yl}imidazo[1,2-a]pyridin-8-yl)-5-(morpholin-4-yl)pyridin-2-amine;

1,5-dimethyl-N-(6-{1H-pyrrolo[3,2-b]pyridin-6-yl}imidazo[1,2-a]pyridin-8-yl)-1H-pyrazol-3-amine;

1-(2-hydroxyethyl)-5-(8-{[5-(morpholin-4-yl)pyridin-2-yl]amino}imidazo[1,2-a]pyridin-6-yl)-2,3-dihydro-1H-1,3-benzodiazol-2-one;

2-[ethyl({6-[(6-{1H-pyrrolo[3,2-b]pyridin-6-yl}imidazo[1,2-a]pyridin-8-yl)amino]pyridin-3-yl})amino]ethan-1-ol;

1-(4-{6-[(6-{1H-pyrrolo[3,2-b]pyridin-6-yl}imidazo[1,2-a]pyridin-8-yl)amino]pyridin-3-yl}piperazin-1-yl)ethan-1-one;

2-[4-({6-[3-(2-hydroxyethyl)-1H-indol-6-yl]imidazo[1,2-a]pyridin-8-yl}amino)phenyl]-2-methylpropan-1-ol;

1-{4-[6-({6-[3-(2-hydroxyethyl)-1H-indol-6-yl]imidazo[1,2-a]pyridin-8-yl}amino)pyridine-3-yl]piperazin-1-yl}ethan-1-one;

2-{5-methyl-3-[(6-{1H-pyrrolo[3,2-b]pyridin-6-yl}imidazo[1,2-a]pyridin-8-yl)amino]-1H-pyrazol-1-yl}ethan-1-ol;

6-(8-{[5-(hydroxymethyl)-1-methyl-1H-pyrazol-3-yl]amino}imidazo[1,2-a]pyridin-6-yl)-2,3-dihydro-1H-indol-2-one;

6-[8-({5-acetyl-4H,5H,6H,7H-pyrazolo[1,5-a]pyrazin-2-yl}amino)imidazo[1,2-a]pyridin-6-yl]-2,3-dihydro-1H-indol-2-one;

2-hydroxy-1-(4-{6-[(6-{1H-pyrrolo[3,2-b]pyridin-6-yl}imidazo[1,2-a]pyridin-8-yl)amino]pyridin-3-yl}piperazin-1-yl)ethan-1-one;

6-(8-{[1-(2-hydroxyethyl)-5-methyl-1H-pyrazol-3-yl]amino}imidazo[1,2-a]pyridin-6-yl)-2,3-dihydro-1H-indol-2-one;

{1-methyl-3-[(6-{1H-pyrrolo[3,2-b]pyridin-6-yl}imidazo[ 1,2-a]pyridin-8-yl)amino]-1H-pyrazol-5-yl}methanol;

6-(8-{[5-methanesulfonyl-4H, 5H,6H,7H-pyrazolo[1,5-a]pyrazin-2-yl}amino)imidazo[1,2-a]pyridin-6-yl]-2,3-dihydro-1H-indol-2-one;

N-{5-methanesulfonyl-4H, 5H,6H,7H-pyrazolo[1,5-a]pyrazin-2-yl}-6-{1H-pyrrolo[3,2-b]pyridin-6-yl}imidazo[1,2-a]pyridin-8-amine;

6-(8-{[5-(4-acetylpiperazin-1-yl)pyridin-2-yl]amino}imidazo[1,2-a]pyridine-6-yl)-2,3-dihydro-1H-indol-2-one; and

5-(4-ethylpiperazin-1-yl)-N-(6-{1H-pyrrolo[3,2-b]pyridin-6-yl}imidazo[1,2-a]pyridin-8-yl)pyridin-2-amine;

or a pharmaceutically acceptable salt, solvate, or solvate of the salt thereof.

11. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt, solvate, or solvate of the salt thereof, and at least one pharmaceutically acceptable vehicle selected from a carrier, adjuvant, and excipient.