Pyrimidine cyclohexyl glucocorticoid receptor modulators

1. A compound of formula I:

wherein

the dashed line is absent or a bond;

X is selected from the group consisting of O and S;

R 1 is selected from the group consisting of cycloalkyl, heterocycloalkyl, aryl and heteroaryl, optionally substituted with from 1 to 3 R 1a groups;

each R 1a is independently selected from the group consisting of H, C 1-6 alkyl, C 2-6 alkenyl,

C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkyl-OR 1b , halogen, C 1-6 haloalkyl,

C 1-6 haloaloxy, —OR 1b , —NR 1b R 1c , —C(O)R 1b , —C(O)OR 1b , —OC(O)R 1b , —C(O)NR 1b R 1c , —NR 1b C(O)R 1c , —SO 2 R 1b , —SO 2 NR 1b R 1c , cycloalkyl, heterocycloalkyl, aryl and heteroaryl;

R 1b and R 1c are each independently selected from the group consisting of H and C 1-6 alkyl;

R 2 is selected from the group consisting of H, C 1-6 alkyl, C 1-6 alkyl-OR 1b , C 1-6 alkyl-NR 1b R 1c and C 1-6 alkylene-heterocycloalkyl;

R 3 is selected from the group consisting of H and C 1-6 alkyl;

Ar is aryl, optionally substituted with 1-4 R 4 groups;

each R 4 is independently selected from the group consisting of H, C 1-6 alkyl, C 1-6 alkoxy, halogen, C 1-6 haloalkyl and C 1-6 haloalkoxy;

L 1 is a bond or C 1-6 alkylene;

subscript n is an integer from 0 to 3,

and salts and isomers thereof.

2. The compound of claim 1 , having formula Ia:

3. The compound of claim 1 , having formula Ib:

4. The compound of claim 1 , having formula Ic:

5. The compound of claim 1 , wherein R 1 is selected from the group consisting of aryl and heteroaryl.

6. The compound of claim 1 , wherein R 1 is selected from the group consisting of phenyl, pyridyl, pyrimidine, and thiazole.

7. The compound of claim 1 , wherein each R 1a is independently selected from the group consisting of H, C 1-6 alkyl, C 1-6 alkoxy, halogen, C 1-6 haloalkyl, —NR 1b R 1c , and —SO 2 R 1b .

8. The compound of claim 1 , wherein each R 1a is C 1-6 haloalkyl.

9. The compound of claim 1 , wherein each R 1a is independently selected from the group consisting of H, Me, Et, —OMe, F, Cl, —CF 3 , —NMe 2 , and —SO 2 Me.

10. The compound of claim 1 , wherein each R 1a is —CF 3 .

11. The compound of claim 1 , wherein R 2 is selected from the group consisting of H and C 1-6 alkyl.

12. The compound of claim 1 , wherein R 2 is H.

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

14. The compound of claim 1 , having the formula:

15. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 1 .