Imidazolopyrazine compounds useful for the treatment of degenerative and inflammatory diseases

1. A compound according to formula IVa, IVb, or IVc:

wherein L is —CON(H)—CH 2 —CH 2 —; the ring P is substituted or unsubstituted heterocycloalkyl; the subscript n, is selected from 1-4; each R 8a is independently selected from hydrogen, substituted or unsubstituted alkyl, alkoxy, cyano, and halo; and R 9 is independently selected from substituted or unsubstituted aryl and heteroaryl; or a pharmaceutically acceptable salt, thereof; or stereoisomers or tautomers thereof.

2. A compound according to formula IVa, IVb, or IVc:

wherein L is —OCH 2 —CH 2 — or —NHCH 2 —CH 2 —; the ring P is substituted or unsubstituted heterocycloalkyl; the subscript n, is selected from 1-4; each R 8a is independently selected from hydrogen, substituted or unsubstituted alkyl, alkoxy, cyano, and halo; and R 9 is independently selected from substituted or unsubstituted aryl and heteroaryl; or a pharmaceutically acceptable salt, thereof; or stereoisomers or tautomers thereof.

3. A compound according to any one of claims 1 and 2 , wherein the ring P is substituted or unsubstituted piperidine, morpholine or piperazine.

4. A compound according to formula III;

wherein

R 1 is H, or substituted or unsubstituted alkyl; R 2 is H, lower alkyl, lower cycloalkyl and lower alkyl-lower cycloalkyl, optionally substituted with one or more of F and Cl; R 8 is

L is selected from a single bond, alkylene, —O—, —N(R 8e )—, —CO—,—CO 2 —, —SO—, —SO 2 —, —CON(R 8e )—, —SO 2 N(R 8e )—, —N(R 8e )CO—, —N(R 8e )SO 2 —, —N(R 8e )CO N(R 8e )—, —N(R 8e )SO 2 N(R 8e )—; —O(CR 8e 2 ) m1 —, or —CON(R 8e )(CR 8e 2 ) m1 —;

each R 8a independently selected from hydrogen, substituted or unsubstituted alkyl, alkoxy, cyano, and halo;

R 8d is selected from substituted or unsubstituted heterocycloalkyl;

R 8e is selected from H, substituted or unsubstituted alkyl and substituted or unsubstituted cycloalkyl;

the subscript m 1 is 1, 2, 3, or 4; the subscript n is 1, 2, 3, or 4;

and wherein R 9 is

and each of A 1 , A 2 and A 3 is independently selected from S, O, N, NR 9a , and CR 9a ; each of R 9a is independently H or substituted or unsubstituted alkyl; and R 9b is CONH 2 , CONHMe, or CN;

or a pharmaceutically acceptable salt, thereof; or stereoisomers or tautomers thereof.

5. A compound according to formula III;

wherein

R 1 is H, or substituted or unsubstituted alkyl; R 2 is H, lower alkyl, lower cycloalkyl and lower alkyl-lower cycloalkyl, optionally substituted with one or more of F and Cl; R 8 is

L is selected from a single bond, alkylene, —O—, —N(R 8e )—, —CO—, —CO 2 —, —SO—, —SO 2 —, —CON(R 8e )—, —SO 2 N(R 8e )—, —N(R 8e )CO—, —N(R 8e )SO 2 —, —N(R 8e )CON(R 8e )—, —N(R 8e )SO 2 N(R 8e )—; —O(CR 8e 2 ) m1 —, or —CON(R 8e )(CR 8e 2 ) m1 —;

each R 8a is independently selected from hydrogen, substituted or unsubstituted alkyl, alkoxy, cyano, and halo;

R 8d is selected from substituted or unsubstituted heterocycloalkyl;

R 8e is selected from H, substituted or unsubstituted alkyl and substituted or unsubstituted cycloalkyl;

the subscript m 1 is 1, 2, 3, or 4; the subscript n is 1, 2, 3, or 4;

and wherein R 9 is

 or a pharmaceutically acceptable salt, thereof; or stereoisomers or tautomers thereof.

6. A compound according to formula III:

wherein

R 1 is H, or substituted or unsubstituted alkyl; R 2 is H, lower alkyl, lower cycloalkyl and lower alkyl-lower cycloalkyl, optionally substituted with one or more of F and Cl; R 8 is

L is selected from a single bond, alkylene, —O—, —N(R 8e )—, —CO—,—CO 2 —, —SO—, —SO 2 —, —CON(R 8e )—, —SO 2 N(R 8e )—,—N(R 8e )CO—, —N(R 8e )SO 2 —, —N(R 8e )CO N(R 8e )—, —N(R 8e )SO 2 N(R 8e )—; —O(CR 8e 2 ) m1 —, or —CON(R 8e )(CR 8e 2 ) m1 —;

each R 8a independently selected from hydrogen, substituted or unsubstituted alkyl, alkoxy, cyano, and halo;

R 8d is selected from substituted or unsubstituted heterocycloalkyl;

R 8e is selected from H, substituted or unsubstituted alkyl and substituted or unsubstituted cycloalkyl;

the subscript m 1 is 1, 2, 3, or 4; the subscript n is 1, 2, 3, or 4;

and wherein R 9 is

or a pharmaceutically acceptable salt, thereof; or stereoisomers or tautomers thereof.

7. A compound according to formula III:

wherein

R 1 is H, or substituted or unsubstituted alkyl; R 2 is H, lower alkyl, lower cycloalkyl and lower alkyl-lower cycloalkyl, optionally substituted with one or more of F and Cl; R 8 is

L is selected from a single bond, alkylene, —O—, —N(R 8e )—,—CO—,—CO 2 —, —SO—, —SO 2 —, —CON(R 8e )—, —SO 2 N(R 8e )—, —N(R 8e )CO—, —N(R 8e )SO 2 —, —N(R 8e )CO N(R 8e )—, —N(R 8e )SO 2 N(R 8e )—; —O(CR 8e 2 ) m1 —, or —CON(R 8e )(CR 8e 2 ) m1 —;

each R 8a is independently selected from hydrogen, substituted or unsubstituted alkyl, alkoxy, cyano, and halo;

R 8d is selected from substituted or unsubstituted heterocycloalkyl;

R 8e is selected from H, substituted or unsubstituted alkyl and substituted or unsubstituted cycloalkyl;

the subscript m 1 is 1, 2, 3, or 4; the subscript n is 1, 2, 3, or 4;

and wherein R 9 is

 and wherein the subscript m is selected from 1-4 and each R 9d is independently H, substituted or unsubstituted alkyl or halo; or a pharmaceutically acceptable salt, thereof; or stereoisomers or tautomers thereof.

8. A compound according to formula III:

wherein

R 1 is H, or substituted or unsubstituted alkyl; R 2 is H, lower alkyl, lower cycloalkyl and lower alkyl-lower cycloalkyl, optionally substituted with one or more of F and Cl; R 8 is

L is selected from a single bond, alkylene, —O—, —N(R 8e )—, —CO—, —CO 2 —, —SO—, —SO 2 —, —CON(R 8e )—, —SO 2 N(R 8e )—, —N(R 8e )CO—, —N(R 8e )SO 2 —, —N(R 8e )CO N(R 8e )—, —N(R 8e )SO 2 N(R 8e )—; —O(CR 8e 2 ) m1 —, or —CON(R 8e )(CR 8e 2 ) m1 —;

each R 8a is independently selected from hydrogen, substituted or unsubstituted alkyl, alkoxy, cyano, and halo;

R 8d is selected from substituted or unsubstituted heterocycloalkyl;

R 8e is selected from H, substituted or unsubstituted alkyl and substituted or unsubstituted cycloalkyl;

the subscript m 1 is 1, 2, 3, or 4; the subscript n is 1, 2, 3, or 4;

wherein R 9 is

and wherein the subscript m is selected from 1-4and each R 9d is independently H, substituted or unsubstituted alkyl or halo; or a pharmaceutically acceptable salt, thereof; or stereoisomers or tautomers thereof.

9. A compound according to formula III:

wherein

R 1 is H, or substituted or unsubstituted alkyl; R 2 is H, lower alkyl, lower cycloalkyl and lower alkyl-lower cycloalkyl, optionally substituted with one or more of F and Cl; R 8 is

L is selected from a single bond, alkylene, —O—, —N(R 8e )—, —CO—,—CO 2 —, —SO—, —SO 2 —, —CON(R 8e )—, —SO 2 N(R 8e )—, —N(R 8e )CO—, —N(R 8e )SO 2 —, —N(R 8e )CO N(R 8e )—, —N(R 8e )SO 2 N(R 8e )—; —O(CR 8e 2 ) m1 —, or —CON(R 8e )(CR 8e 2 ) m1 —;

each R 8a is independently selected from hydrogen, substituted or unsubstituted alkyl, alkoxy, cyano, and halo;

R 8d is selected from substituted or unsubstituted heterocycloalkyl;

r 8e is selected from H, substituted or unsubstituted alkyl and substituted or unsubstituted cycloalkyl;

the subscript m 1 is 1, 2, 3, or 4; the subscript n is 1, 2, 3, or 4;

wherein R 9 is

and wherein the subscript m is selected from 1-3 and each R 9d is independently H, substituted or unsubstituted alkyl or halo; or a pharmaceutically acceptable salt, thereof; or stereoisomers or tautomers thereof.

10. A compound of formula VIa, VIb, VId, or VIe:

wherein R 8b is hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted cycloalkyl.

11. A compound of formula VIIa, VIIb, VIId, or VIIe:

wherein R 8b is hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted cycloalkyl.

12. A compound of formula VIIIa, VIIIb, VIIId, or VIIIe:

wherein R 8b is hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted cycloalkyl.

13. A compound of formula IXa, IXb, IXd, or IXe:

wherein R 8b is hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted cycloalkyl.

14. A compound of formula Xa, Xb, Xd, or Xe:

wherein R 8b is hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted cycloalkyl.

15. A compound of formula XIa, XIb, XId, or XIe:

wherein R 8b is hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted cycloalkyl; and R 9e is hydrogen, Me, or CN.

16. A compound according to any one of claims 10 - 15 , wherein R 8b is H.

17. A compound according to any one of claims 10 - 15 , wherein R 8b is cycloalkyl.

18. A compound according to any one of claims 10 - 15 , wherein R 8b is cyclopropyl.

19. A compound according to any one of claims 10 - 15 , wherein R 8b is substituted or unsubstituted alkyl.

20. A compound according to any one of claims 10 - 15 , wherein R 8b is Me, Et, Pr, i-Pr, t-Bu, i-Bu, CF 3 , CH 2 CF 3 , CH 2 CONH 2 , or cyclopropylmethyl.

21. A compound of formula XIIa, XIIb, XIIc or XIId:

22. A compound of formula XIIIa, XIIIb, XIIIc or XIIId:

23. A compound of formula XVa, or XVb:

wherein L is a single bond, —CO—,or —O—CH 2 —CH 2 —; the ring P is

and R 8b is H, Me, i-Pr, t-Bu, CH 2 CONH 2 , cyclopropylmethyl, or CH 2 CF 3 .

24. A compound according to claim 23 , wherein L is a bond and the ring P is

25. A compound selected from

(4-Morpholin-4-yl-phenyl)-[5-(1H-pyrazol-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-amine;

4-[8-(4-Morpholin-4-yl-phenylamino)-imidazo[1,2-a]pyrazin-5-yl]-benzamide;

[4-(4-Methylpiperazin-1-yl)-phenyl]-[5-(1H-pyrazol-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-amine;

4-{8-[4-(4-Methyl-piperazin- 1-yl)-phenylamino]-imidazo [1,2-a]pyrazin-5-yl}-benzamide;

Morpholin-4-yl-{4-[5-(1H-pyrazol-4-yl)-imidazo[1,2-a]pyrazin-8-ylamino]-phenyl}-methanone;

N-(2-Morpholin-4-yl-ethyl)-4-[5-(1H-pyrazol-4-yl)-imidazo[1,2-a]pyrazin-8-ylamino]-benzamide;

4-{8-[4-(2-Morpholin-4-yl-ethylcarbamoyl)-phenylamino]-imidazo[1,2-a]pyrazin-5-yl}-benzoic acid;

4-[5-(1H-pyrazol-4-yl)-imidazo[1,2-a]pyrazin-8-ylamino]-N-pyrrolidin-3-yl-benzamide;

N-(1-Methyl-pyrrolidin-3-yl)-4-[5-(1H-pyrazol-4-yl)-imidazo[1,2-a]pyrazin-8-ylamino]-benzamide;

[4-(4-Methyl-piperazine-1-sulfonyl)-phenyl]-[5-(1H-pyrazol-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-amine;

4- {8-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-imidazo[1,2-a]pyrazin-5-yl}-1H-pyridin-2-one;

4-{8-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-imidazo[1,2-a]pyrazin-5-yl}-thiophene-2-carboxylic acid amide;

[4-(4-Methyl-piperazin-1-yl)-phenyl]-[5-(5-methyl-1H-pyrazol-4-yl)-imidazo [1,2-a]pyrazin-8-yl]-amine;

3-Methyl-4-{8-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-imidazo[1,2-a]pyrazin-5-yl}-benzamide;

2-Fluoro-4-{8-[4-(4-methyl-piperazin-1-yl)-phenylamino]-imidazo[1,2-a]pyrazin-5-yl}-benzamide;

3-Fluoro-4-{ 8 -[4-(4-methyl-piperazin-1-yl)-phenylamino]-imidazo[1,2-a]pyrazin-5-yl}-benzamide;

2-Chloro-4-{8-[4-(4-methyl-piperazin-1-yl)-phenylamino]-imidazo[1,2-a]pyrazin-5-yl}-benzamide;

5-{8-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-imidazo[1,2-a]pyrazin-5-yl}-thiophene-2-carboxylic acid amide;

4-(8-(3-chloro-4-(4-methylpiperazin-1-yl)phenylamino)imidazo[1,2-a]pyrazin-5-yl)benzamide;

4-(8-(4-((2R,5S)-2,4,5-trimethylpiperazin-1-yl)phenylamino)imidazo[1,2-a]pyrazin-5-yl) benzamide;

5-(8-(4-(4-methylpiperazin-1-yl)phenylamino)imidazo[1,2-a]pyrazin-5-yl)furan-2-carboxamide;

2,6-difluoro-4-(8-(4-(4-methylpiperazin-1-yl)phenylamino)imidazo[1,2-a]pyrazin-5-yl)benzamide;

4-(8(4-(4-isopropylpiperazin-1-yl)phenylamino)imidazo[1,2-a]pyrazin-5-yl)benzamide;

4-(8-(6-(4-methylpiperazin-1-yl)pyridin-3-ylamino)imidazo[1,2-a]pyrazin-5-yl)benzamide;

5-(8-(4-(4-methylpiperazin- 1-yl)phenylamino)imidazo [1,2-a]pyrazin-5-yl)thiophene-3-carboxamide;

5-(8-(4-(4-methylpiperazin-1-yl)phenylamino)imidazo[1,2-a]pyrazin-5-yl)furan-3-carboxamide;

2-fluoro-4-(8-(4-(2-morpholinoethoxy)phenylamino)imidazo[1,2-a]pyrazin-5-yl)benzamide;

N-(4-(2-morpholinoethoxy)phenyl)-5-(1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-amine;

5-(8-(4-morpholinophenylamino)imidazo[1,2-a]pyrazin-5-yl)thiophene-2-carboxamide;

4-(8-(4-((3S,5R)-3,4,5-trimethylpiperazin-1-yl)phenylamino)imidazo[1,2-a]pyrazin-5-yl)benzamide;

4-(8-(4-(4-(2-hydroxyethyl)piperazin-1-yl)phenylamino)imidazo[1,2-a]pyrazin-5-yl)benzamide;

2-(8-(4-morpholinophenylamino)imidazo[1,2-a]pyrazin-5-yl)thiazole-5-carboxamide;

2,6-Difluoro-4-[8-(4-morpholin-4-yl-phenylamino)-imidazo[1,2-a]pyrazin-5-yl]-benzamide;

4-(8-(3-fluoro-4-(4-methylpiperazin-1-yl)phenylamino)imidazo[1,2-a]pyrazin-5-yl)benzamide;

4-(8-(3-morpholinophenylamino)imidazo[1,2-a]pyrazin-5-yl)benzamide;

4-(8-(3-carbamoyl-4-morpholinophenylamino)imidazo[1,2-a]pyrazin-5-yl)-2,6-difluorobenzamide;

5-(5-methyl-1H-pyrazol-4-yl)-N-(4-morpholinophenyl)imidazo[1,2-a]pyrazin-8-amine;

4-(8-(4-morpholinophenylamino)imidazo[1,2-a]pyrazin-5-yl)thiophene-2-carboxamide;

5-(8-(4-morpholinophenylamino)imidazo[1,2-a]pyrazin-5-yl)isoindolin-1-one;

5-(8-(4-morpholinophenylamino)imidazo[1,2-a]pyrazin-5-yl)furan-3-carboxamide;

2,6-difluoro-4-(8-(4-((2S,5R)-2,4,5-trimethylpiperazin-1-yl)phenylamino)imidazo[1,2-a]pyrazin-5-yl)benzamide;

2-methyl-4-(8-(4-morpholinophenylamino)imidazo[1,2-a]pyrazin-5-yl)benzamide;

4-(8-(4((2S,5R)-2,4,5-trimethylpiperazin-1-yl)phenylamino)imidazo[1,2-a]pyrazin-5-yl)thiophene-2-carboxamide;

5-(8-(4((2S,5R)-2,4,5-trimethylpiperazin-1-yl)phenylamino)imidazo[1,2-a]pyrazin-5-yl)furan-3-carboxamide;

5-[8-(4-Piperazin-1-yl-phenylamino)-imidazo[1,2-a]pyrazin-5-yl]-furan-3-carboxylic acid amide;

2,6-difluoro-4-(8-(4-(4-isopropylpiperazin-1-yl)phenylamino)imidazo[1,2-a]pyrazin-5-yl)benzamide;

5-{8-[4-(4-Isopropyl-piperazin-1-yl)-phenylamino]-imidazo[1,2-a]pyrazin-5-yl}-2,3-dihydro-isoindol-1-one;

4-{8-[4-(4-Isopropyl-piperazin-1-yl)-phenylamino]-imidazo[1,2-a]pyrazin-5-yl}-furan-2-carboxylic acid amide;

4-[8-(4-Morpholin-4-yl-phenylamino)-imidazo[1,2-a]pyrazin-5-yl]-furan-2-carboxylic acid amide;

[6-(4-Isopropyl-piperazin-1-yl)-pyridin-3-yl]-[5-(1H-pyrazol-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-amine;

(5-Morpholin-4-yl-pyridin-2-yl)-[5-(1H-pyrazol-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-amine;

5-[8-(5-Morpholin-4-yl-pyridin-2-ylamino)-imidazo[1,2-a]pyrazin-5-yl]- 2 ,3-dihydro-isoindol-1-one;

4-[8-(4-Morpholin-4-yl-phenylamino)-imidazo[1,2-a]pyrazin-5-yl]-2H-pyrazole-3-carbonitrile;

5-{8-[6-(4-Isopropyl-piperazin-1-yl)-pyridin-3-ylamino]-imidazo[1,2-a]pyrazin-5-yl}-2,3-dihydro-isoindol-1-one;

4-{8-[6-(4-Isopropyl-piperazin-1-yl)-pyridin-3-ylamino]-imidazo[1,2-a]pyrazin-5-yl}-furan-2-carboxylic acid amide; and

pharmaceutically acceptable salts thereof

26. A compound selected from

4-[3-Methyl-8-(4-morpholin-4-yl-phenylamino)-imidazo[1,2-a]pyrazin-5-yl]-benzamide;

[3-Methyl-5-(1H-pyrazol-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-(4-morpholin-4-yl-phenyl)-amine;

4-[3-Methyl-8-(4-morpholin-4-yl-phenylamino)-imidazo[1,2-a]pyrazin-5-yl]-1H-pyridin-2-one;

4-[3-Ethyl-8-(4-morpholin-4-yl-phenylamino)-imidazo[1,2-a]pyrazin-5-yl]-benzamide;

4-[3-Ethyl-8-(4-morpholin-4-yl-phenylamino)-imidazo[1,2-a]pyrazin-5-yl]-1H-pyridin-2-one;

[3-Ethyl-5-(1H-pyrazol-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-(4-morpholin-4-yl-phenyl)-amine;

[6-(4-Isopropyl-piperazin-1-yl)-pyridin-3-yl]-[5-(1H-pyrazol-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-amine;

5-[8-(6-Morpholin-4-yl-pyridin-3-ylamino)-imidazo[1,2-a]pyrazin-5-yl]-2,3-dihydro-isoindol-1-one;

2,6-Difluoro-4-{8-[4-(2-morpholin-4-yl-ethoxy)-phenylamino]-imidazo[1,2-a]pyrazin-5-yl}-benzamide;

2-[8-(4-Morpholin-4-yl-phenylamino)-imidazo[1,2-a]pyrazin-5-yl]- 5 , 6 -dihydro-furo[2,3-c]pyrrol-4-one;

(3-Dimethylaminomethyl-4-morpholin-4-yl-phenyl)-[5-(1H-pyrazol-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-amine;

7-Fluoro-5-{8-[4-(4-isopropyl-piperazin-1-yl)-phenylamino]-imidazo[1,2-a]pyrazin-5-yl}-2,3-dihydro-isoindol-1-one;

2-{8-[4-(4-Isopropyl-piperazin-1-yl)-phenylamino]-imidazo[1,2-a]pyrazin-5-yl}-5,6-dihydro-furo[2,3-c]pyrrol-4-one;

5-{8-[4-(4-Isopropyl-piperazin-1-yl)-phenylamino]-imidazo[1,2-a]pyrazin-5-yl}-3,3-dimethyl-2,3-dihydro-isoindol-1-one;

2-{8-[4-(4-Isopropyl-piperazin-1-yl)-phenylamino]-imidazo[1,2-a]pyrazin-5-yl}-4,5-dihydro-thieno[2,3-c]pyrrol-6-one; and

pharmaceutically acceptable salts thereof.

27. A compound selected from

(4-Morpholin-4-yl-phenyl)-[5-(1H-pyrazol-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-amine;

Morpholin-4-yl-{4-[5-(1H-pyrazol-4-yl)-imidazo[1,2-a]pyrazin-8-ylamino]-phenyl}-methanone;

N-(2-Morpholin-4-yl-ethyl)-4-[5-(1H-pyrazol-4-yl)-imidazo[1,2-a]pyrazin-8-ylamino]-benzamide;

[4-(4-Methyl-piperazine-1-sulfonyl)-phenyl]-[5-(1H-pyrazol-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-amine;

4-[8-(4-Morpholin-4-yl-phenylamino)-imidazo[1,2-a]pyrazin-5-yl]-1H-pyridin-2-one;

4-{8-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-imidazo[1,2-a]pyrazin-5-yl}-1H-pyridin-2-one;

4-{8-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-imidazo[1,2-a]pyrazin-5-yl}-thiophene-2-carboxylic acid amide;

[4-(4-Methyl-piperazin-1-yl)-phenyl]-[5-(5-methyl-1H-pyrazol-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-amine;

2-Fluoro-4-{8-[4-(4-methyl-piperazin-1-yl)-phenylamino]-imidazo[1,2-a]pyrazin-5-yl}-benzamide;

3-Fluoro-4-{8-[4-(4-methyl-piperazin-1-yl)-phenylamino]-imidazo[1,2-a]pyrazin-5-yl}-benzamide;

5-{8-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-imidazo[1,2-a]pyrazin-5-yl}-thiophene-2-carboxylic acid amide; and

pharmaceutically acceptable salts thereof.

28. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound of any one of claims 25 , 26 and 27 .

29. The pharmaceutical composition of claim 28 , wherein the carrier is a parenteral carrier.

30. The pharmaceutical composition of claim 28 , wherein the carrier is an oral carrier.

31. The pharmaceutical composition of claim 28 , wherein the carrier is a topical carrier.

32. A compound according to claim 4 , wherein R 8 is

33. A compound according to formula IVa, IVb, or IVc:

and wherein L is a single bond, —CO—,—O(CH 2 ) m1 —, —CON(H)(CH 2 ) m1 —, or —NHCO—; the subscript m 1 is selected from 1-4; the ring P is substituted or unsubstituted heterocycloalkyl; the subscript n, is selected from 1-4; each R 8a is independently selected from hydrogen, substituted or unsubstituted alkyl, alkoxy, cyano, and halo; and R 9 is

and each of A 1 , A 2 and A 3 is independently selected from S, O, N, NR 9a , and CR 9a ; each of R 9a is independently H or substituted or unsubstituted alkyl; and R 9b is CONH 2 , CONHMe, or CN; or a pharmaceutically acceptable salt, thereof; or stereoisomers or tautomers thereof.

34. A compound according to claim 4 , wherein the compound is according to formula Va, Vb, Vd, or Ve:

and wherein R 8b is hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted cycloalkyl.

35. A compound according to claim 5 , wherein R 8 is

36. A compound according to formula IVa, IVb, or IVc:

and wherein L is a single bond, —CO—, —O(CH 2 ) m1 —, —CON(H)(CH 2 ) m1 —, or —NHCO—; the subscript m 1 is selected from 1-4; the ring P is substituted or unsubstituted heterocycloalkyl; the subscript n, is selected from 1-4; each R 8a independently selected from hydrogen, substituted or unsubstituted alkyl, alkoxy, cyano, and halo; and R 9 is

 or a pharmaceutically acceptable salt, thereof; or stereoisomers or tautomers thereof.

37. A compound according to claim 5 , wherein the compound is according to formula Va, Vb, Vd, or Ve:

and wherein R 8b is hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted cycloalkyl.

38. A compound according to claim 6 , wherein R 8 is

39. A compound according to formula IVa, IVb, or IVc:

and wherein L is a single bond, —CO—,—O(CH 2 ) m1 —, —CON(H)(CH 2 ) m1 —, or —NHCO—; the subscript m 1 is selected from 1-4; the ring P is substituted or unsubstituted heterocycloalkyl; the subscript n, is selected from 1-4; each R 8a is independently selected from hydrogen, substituted or unsubstituted alkyl, alkoxy, cyano, and halo; and R 9 is

or a pharmaceutically acceptable salt, thereof; or stereoisomers or tautomers thereof.

40. A compound according to claim 6 , wherein the compound is according to formula Va, Vb, Vd, or Ve:

and wherein R 8b is hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted cycloalkyl.

41. A compound according to claim 7 , wherein R 8 is

42. A compound according to formula IVa, IVb, or IVc:

and wherein L is a single bond, —CO—,—O(CH 2 ) m1 —, —CON(H)(CH 2 ) m1 —, or —NHCO—; the subscript m 1 is selected from 1-4; the ring P is substituted or unsubstituted heterocycloalkyl; the subscript n, is selected from 1-4; each R 8a is independently selected from hydrogen, substituted or unsubstituted alkyl, alkoxy, cyano, and halo; and R 9 is

 and wherein the subscript m is selected from 1-4and each R 9d is independently H, substituted or unsubstituted alkyl or halo; or a pharmaceutically acceptable salt, thereof; or stereoisomers or tautomers thereof.

43. A compound according to claim 7 , wherein the compound is according to formula Va, Vb, Vd, or Ve:

and wherein R 8b is hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted cycloalkyl.

44. A compound according to claim 8 , wherein R 8 is

45. A compound according to formula IVa, IVb, or IVc:

and wherein L is a single bond, —CO—,—O(CH 2 ) m1 —, —CON(H)(CH 2 ) m1 —, or —NHCO—; the subscript m 1 is selected from 1-4; the ring P is substituted or unsubstituted heterocycloalkyl; the subscript n, is selected from 1-4; each R 8a is independently selected from hydrogen, substituted or unsubstituted alkyl, alkoxy, cyano, and halo; and R 9 is

 and wherein the subscript m is selected from 1-4and each R 9d is independently H, substituted or unsubstituted alkyl or halo; or a pharmaceutically acceptable salt, thereof; or stereoisomers or tautomers thereof.

46. A compound according to claim 8 , wherein the compound is according to formula Va, Vb, Vd, or Ve:

and wherein R 8b is hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted cycloalkyl.

47. A compound according to claim 9 , wherein R 8 is

48. A compound according to formula IVa, IVb, or IVc:

and wherein L is a single bond, —CO—,—O(CH 2 ) m1 —, —CON(H)(CH 2 ) m1 —, or —NHCO—; the subscript m 1 is selected from 1-4; the ring P is substituted or unsubstituted heterocycloalkyl; the subscript n, is selected from 1-4; each R 8a is independently selected from hydrogen, substituted or unsubstituted alkyl, alkoxy, cyano, and halo; and R 9 is

and wherein the subscript m is selected from 1-3 and each R 9d is independently H, substituted or unsubstituted alkyl or halo; or a pharmaceutically acceptable salt, thereof; or stereoisomers or tautomers thereof.

49. A compound according to claim 9 , wherein the compound is according to formula Va, Vb, Vd, or Ve:

and wherein R 8b is hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted cycloalkyl.

50. A compound according to any one of claims 7 , 41 , 42 and 43 , wherein each R 9d is H.

51. A compound according to any one of claims 7 , 41 , 42 and 43 , wherein m is 1 or 2 and each R 9d is Me, Cl or F.

52. A compound according to any one of claims 8 , 44 , 45 and 46 , wherein each R 9d is H.

53. A compound according to any one of claims 9 , 47 , 48 and 49 , wherein each R 9d is H.

54. A compound according to any one of claims 8 , 44 , 45 and 46 , wherein m is 1 or 2 and each R 9d is Me, Cl or F.

55. A compound according to any one of claims 9 , 47 , 48 and 49 , wherein m is 1 or 2 and each R 9d is Me, Cl or F.