Pyrimidine cyclohexenyl glucocorticoid receptor modulators

1. A compound of formula Ic-1:

or a pharmaceutically acceptable salt thereof, or an isomer thereof,

wherein

each R b is independently H, halogen, CN, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 hydroxyalkyl, C 1-4 haloalkyl, C 1-4 haloalkoxy, —OR b4 , —NR b1 R b2 , —C(O)NR b1 R b2 , —SO 2 R b1 , —SO 2 NR b1 R b2 , or C 3-6 cycloalkyl;

R b1 and R b2 are each independently H or C 1-4 alkyl; or R b1 and R b2 when attached to a nitrogen atom are combined to form a 4-6 membered heterocycle having 1-2 nitrogen atoms, which is optionally substituted with 1-2 R b3 ;

each R b3 is independently H, halogen, C 1-4 alkyl, or C 1-4 alkoxy; and

each R b4 is independently C 1-4 hydroxyalkyl, C 3-6 cycloalkyl or C 3-6 cycloalkyl-C 1-4 alkyl.

2. The compound of claim 1 , wherein

each R b is independently H, halogen, CN, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 hydroxyalkyl, C 1-4 haloalkyl, or C 1-4 haloalkoxy.

3. The compound of claim 1 , wherein

each R b is independently H, F, Cl, CN, Me, Et, nPr, iPr, nBu, iBu, sBu, tBu, OMe, OEt, OnPr, OiPr, CH 2 F, CHF 2 , CF 3 , CH 2 CF 3 , OCH 2 F, OCHF 2 , OCF 3 , OCH 2 CF 3 , —CH 2 OH, —OCH 2 CH 2 OH, —O-cyclopropyl, —O-cyclobutyl, —O-cyclopentyl, —O— cyclohexyl, —O-cyclopropylmethyl, —O-cyclobutylmethyl, —O-cyclopentylmethyl, —O-cyclohexylmethyl, —NH 2 , —NHMe, —NMe 2 , —SO 2 Me, —SO 2 Et, —S(O) 2 iPr, —S(O) 2 NHMe, —S(O) 2 NMe 2 , 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl, —C(O)-1-pyrrolidinyl, —C(O)-1-piperidinyl, —C(O)-1-piperazinyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, wherein

each of 1-pyrrolidinyl, 1-piperidinyl, and 1-piperazinyl is optionally substituted with 1-2 R b3 ; and

each R b3 is independently H, F, Me, or OMe.

4. The compound of claim 1 , wherein

each R b is independently H, F, Cl, CN, Me, Et, iBu, OMe, OEt, OiPr, CF 3 , OCHF 2 , OCF 3 , OCH 2 CF 3 , —CH 2 OH, —OCH 2 CH 2 OH, —O-cyclopropyl, —O— cyclopropylmethyl, —NMe 2 , —S(O) 2 Me, —S(O) 2 Et, —S(O) 2 iPr, —S(O) 2 NHMe, —S(O) 2 NMe 2 , 1-pyrrolidinyl, 1-piperidinyl, 4,4-difluoro-1-piperidinyl, 3,3-dimethyl-1-piperidinyl, 3-methyl-1-piperidinyl, 3-methoxy-1-piperidinyl, —C(O)-1-pyrrolidinyl, —C(O)-4-methyl-1-piperazinyl, or cyclopropyl.

5. The compound of claim 1 , wherein each R b is independently H, F, Cl, CN, Me, CF 3 , OCF 3 , or —CH 2 OH.

6. The compound of claim 1 , wherein R 1 is H.

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

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

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

10. The compound of claim 7 , selected from the group consisting of:

11. The compound of claim 10 , wherein the compound is:

12. The compound of claim 10 , wherein the compound is:

13. The compound of claim 10 , wherein the compound is:

14. A pharmaceutical composition comprising one or more pharmaceutically acceptable excipients and a compound of claim 1 .