Compounds and compositions as protein kinase inhibitors

1. A compound of Formula I or II

wherein:

R1 is (C1-C3)alkyl optionally substituted with cyano, —C(O)NH2, or hydroxy,

or R1 is —X1NHC(O)OR1a or —X1NHC(O)NHR1a, where X1 is (C1-C4)alkylene optionally substituted with 1 to 3 groups each independently selected from (C1-C4)alkyl and halosubstituted(C1-C4)alkyl, and R1a is (C1-C4)alkyl or halosubstituted(C1-C4)alkyl;

R1b is H or methyl;

R2 is H or halogen;

R3 is H, halogen, (C1-C4)alkoxy, (C1-C4)alkyl, halosubstituted(C1-C4)alkoxy, or halosubstituted(C1-C4)alkyl;

R4 is halogen, H, or (C1-C4)alkyl;

R5 is (C1-C6)alkyl, (C3-C6)cycloalkyl, (C3-C8)branched alkyl, halosubstituted(C1-C6)alkyl, or halosubstituted(C3-C8)branched alkyl;

R6 is H, (C1-C4)alkyl, or halogen; and

R7 is (C1-C6)alkyl, (C3-C6)cycloalkyl, 1-methyl-(C3-C6)cycloalkyl, or (C3-C8)branched alkyl;

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 wherein said compound is a compound of Formula I;

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 , wherein:

R1 is —X1NHC(O)OR1a, where X1 is a (C1-C4)alkylene optionally substituted with 1 to 3 groups each independently selected from (C1-C4)alkyl or halosubstituted(C1-C4)alkyl and R1a is (C1-C2)alkyl or halosubstituted(C1-C2)alkyl;

R2 is H or F;

R3 is H, halogen, (C1-C2)alkoxy, (C1-C2)alkyl, halosubstituted(C1-C2)alkoxy, or halosubstituted(C1-C2)alkyl;

R4 is H or methyl;

R5 is (C1-C4)alkyl, (C3-C6)cycloalkyl, (C3-C5)branched alkyl, halosubstituted(C1-C4)alkyl, or halosubstituted(C3-C6)branched alkyl; and

R7 is (C3-C6)cycloalkyl, 1-methyl-(C3-C6)cycloalkyl, or (C3-C6)branched alkyl;

or a pharmaceutically acceptable salt thereof.

4. The compound of claim 2 , wherein:

R1 is —X1NHC(O)OR1a, where X1 is a (C1-C4)alkylene optionally substituted with 1 to 3 groups each independently selected from (C1-C4)alkyl or halosubstituted(C1-C4)alkyl and R1a is (C1-C2)alkyl or halosubstituted(C1-C2)alkyl;

R2 is H or F;

R3 is H, halogen, (C1-C2)alkyl, or halosubstituted(C1-C2)alkyl;

R4 is H or methyl;

R5 is (C1-C4)alkyl, (C3-C6)cycloalkyl, halosubstituted(C1-C4)alkyl, or (C3-C5)branched alkyl;

R6 is H, (C1-C2)alkyl, or halogen; and

R7 is (C3-C6)cycloalkyl, 1-methyl-(C3-C6)cycloalkyl, or (C3-C6)branched alkyl;

or a pharmaceutically acceptable salt thereof.

5. The compound of claim 4 , wherein:

R1 is —X1NHC(O)OR1a, where X1 is (C1-C2)alkylene substituted with (C1-C2)alkyl and R1a is (C1-C2)alkyl;

R2 is H;

R3 is H, Cl, F, or methyl;

R4 is H;

R5 is methyl, cyclopropyl, ethyl, propyl, isopropyl, sec-butyl, isobutyl, trifluoromethyl, or 3,3,3-trifluoropropyl;

R6 is H, methyl, F, or Cl; and

R7 is t-butyl, cyclopropyl, or 1-methylcyclopropyl;

or a pharmaceutically acceptable salt thereof.

6. The compound of claim 1 wherein R1 has the following formula (1a)

or a pharmaceutically acceptable salt thereof.

7. The compound of claim 5 wherein R1 has the following formula (1a)

or a pharmaceutically acceptable salt thereof.

8. The compound of claim 1 wherein said compound is a compound of Formula I

wherein

R1 is —X1NHC(O)OR1a, where X1 is (C1-C4)alkylene optionally substituted with 1 to 3 groups each independently selected from halo, (C1-C4)alkyl, and halosubstituted(C1-C4)alkyl, and R1a is H, (C1-C4)alkyl, or halosubstituted(C1-C4)alkyl;

R2 is H or halogen;

R3 is halogen, (C1-C4)alkyl, or halosubstituted(C1-C4)alkyl;

R4 is H, or (C1-C4)alkyl;

R5 is (C1-C6)alkyl, (C3-C6)cycloalkyl, (C3-C8)branched alkyl, or halosubstituted(C1-C6)alkyl;

R6 is halogen; and

R7 is (C1-C6)alkyl, (C3-C6)cycloalkyl, 1-methyl-(C3-C6)cycloalkyl, or (C3-C8)branched alkyl;

or a pharmaceutically acceptable salt thereof.

9. The compound of claim 1 wherein said compound is a compound of Formula II;

or a pharmaceutically acceptable salt thereof.

10. The compound of claim 9 wherein

R2 is H or F;

R3 is halogen;

R4 is H or methyl;

R5 is (C1-C4)alkyl, (C3-C6)cycloalkyl, (C3-C5)branched alkyl, or halosubstituted(C1-C4)alkyl;

R6 is (C1-C2)alkyl, or halogen; and

R7 is (C3-C6)cycloalkyl, 1-methyl-(C3-C6)cycloalkyl, or (C3-C6)branched alkyl;

or a pharmaceutically acceptable salt thereof.

11. The compound of claim 10 wherein

R2 is H;

R3 is Cl or F;

R4 is H;

R5 is methyl, cyclopropyl, ethyl, propyl, isopropyl, sec-butyl, isobutyl, trifluoromethyl, or 3,3,3-trifluoropropyl;

R6 is F or Cl; and

R7 is t-butyl, cyclopropyl, or 1-methylcyclopropyl;

or a pharmaceutically acceptable salt thereof.

12. The compound of claim 11 , wherein R5 is methyl, ethyl, or cyclopropyl.

13. The compound of claim 1 selected from the group consisting of

(S)-Methyl 1-(4-(4-(2-chloro-5-fluoro-3-(methylsulfonamido)phenyl)-2-cyclopropyl-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate;

(S)-Methyl 1-(4-(2-cyclopropyl-4-(2-fluoro-5-methyl-3-(methylsulfonamido)phenyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate;

(S)-Methyl 1-(4-(2-cyclopropyl-4-(2,5-dichloro-3-(methylsulfonamido)phenyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate;

(S)-Methyl 1-(4-(4-(2-chloro-3-(methylsulfonamido)phenyl)-2-cyclopropyl-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate;

(S)-Methyl 1-(4-(2-cyclopropyl-4-(2-fluoro-3-(methylsulfonamido)phenyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate;

Methyl (2S)-1-(4-(2-cyclopropyl-4-(2,5-difluoro-3-(methylsulfonamido)phenyl)-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate; and

(S)-Methyl 1-(4-(4-(2-chloro-5-methyl-3-(methylsulfonamido)phenyl)-2-cyclopropyl-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate;

or a pharmaceutically acceptable salt thereof.

14. A compound selected from the group consisting of

(S)-Methyl 1-(4-(5-(5-chloro-2-fluoro-3-(3,3,3-trifluoropropylsulfonamido)phenyl)-2-cyclopropyl-1H-imidazol-4-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate;

(S)-Methyl 1-(4-(5-(5-chloro-3-(cyclopropylmethylsulfonamido)-2-fluorophenyl)-2-cyclopropyl-1H-imidazol-4-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate;

(S)-Methyl 1-(4-(4-(2-chloro-3-(ethylsulfonamido)-5-fluorophenyl)-2-cyclopropyl-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate; and

(S)-Methyl 1-(4-(4-(2-chloro-3-(cyclopropanesulfonamido)-5-fluorophenyl)-2-cyclopropyl-1H-imidazol-5-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate;

or a pharmaceutically acceptable salt thereof.

15. A pharmaceutical composition comprising a compound of claim 1 and a diluent, carrier or excipient.

16. The pharmaceutical composition of claim 15 , further comprising an additional therapeutic agent, wherein said additional therapeutic agent is selected from the group consisting of an anticancer compound, an analgesic, an antiemetic, an antidepressant, and an anti-inflammatory agent.