Azadecalin Glucocorticoid receptor modulators

1. A compound having the formula:

wherein:

L 4 is selected from a bond, substituted or unsubstituted alkylene, and substituted or unsubstituted heteroalkylene;

L 3 is unsubstituted methylene;

the dashed line b is optionally a bond;

R 3 has the formula:

wherein

q is an integer selected from 1 to 5;

R 3D is a member independently selected from hydrogen, halogen, —OH, —COOH, —CF 3 , —NH 2 , —SH, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —NR 3D1 R 3D2 , —OR 3D3 , —C(O)NR 3D4 R 3D5 , and —C(O)R 3D6 , wherein

R 3D1 , R 3D2 , R 3D3 , R 3D4 , R 3D5 , and R 3D6 are members independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl, wherein

R 3D1 and R 3D2 are optionally joined to form a substituted or unsubstituted ring with the nitrogen to which they are attached, and

R 3D4 and R 3D5 are optionally joined to form a substituted or unsubstituted ring with the nitrogen to which they are attached;

R 4 has the formula:

wherein

R 4G is a member independently selected from hydrogen, halogen, —OH, —COOH, —CF 3 , —NH 2 , —SH, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;

A is a substituted or unsubstituted ring selected from substituted or unsubstituted (C 3 -C 7 )cycloalkyl, substituted or unsubstituted 3-7 membered heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;

X is a member selected from a bond, —S(O) v —, and —S(O) v NR 4I —, wherein

R 4I is a member selected from hydrogen, substituted or unsubstituted alkyl, and substituted or unsubstituted heteroalkyl, and

v is 0, 1, or 2; and

w is an integer from 1 to 5.

2. The compound of claim 1 , wherein the dashed line b is a bond.

3. The compound of claim 1 , wherein

q is an integer selected from 1 to 3; and

R 3D is a member independently selected from hydrogen, substituted alkyl, substituted or unsubstituted heteroalkyl, substituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted aryl, and substituted or unsubstituted heteroaryl.

4. The compound of claim 1 , wherein

R 3D is a member independently selected from hydrogen, R 3D7 -substituted (C 1 -C 10 )alkyl, R 3D7 -substituted or unsubstituted 2-10 membered heteroalkyl, R 3D7 -substituted or unsubstituted (C 3 -C 8 )cycloalkyl, R 3D7 -substituted or unsubstituted 3-8 membered heterocycloalkyl, R 3D8 -substituted or unsubstituted aryl, R 3D8 -substituted or unsubstituted heteroaryl, —NR 3D1 R 3D2 , —OR 3D3 , —C(O)NR 3D4 R 3D5 , and —C(O)R 3D6 , wherein

R 3D1 , R 3D2 , R 3D3 , R 3D4 , R 3D5 , and R 3D6 are members independently selected from hydrogen, R 3D7 -substituted or unsubstituted alkyl, R 3D7 -substituted or unsubstituted heteroalkyl, R 3D7 -substituted or unsubstituted cycloalkyl, R 3D7 -substituted or unsubstituted heterocycloalkyl, R 3D8 -substituted or unsubstituted aryl, and R 3D8 -substituted or unsubstituted heteroaryl,

wherein R 3D1 and R 3D2 are optionally joined with the nitrogen to which they are attached to form a R 3D7 -substituted or unsubstituted heterocycloalkyl, or R 3D8 -substituted or unsubstituted heteroaryl, and

wherein R 3D4 and R 3D5 are optionally joined with the nitrogen to which they are attached to form a R 3D7 -substituted or unsubstituted heterocycloalkyl, or R 3D8 -substituted or unsubstituted heteroaryl,

wherein

R 3D7 is a member selected from halogen, oxo, —OH, —COOH, —CF 3 , —NH 2 , —SH, R 3D9 -substituted or unsubstituted (C 1 -C 10 )alkyl, R 3D9 -substituted or unsubstituted 2-10 membered heteroalkyl, R 3D9 -substituted or unsubstituted (C 3 -C 8 )cycloalkyl, R 3D9 -substituted or unsubstituted 3-8 membered heterocycloalkyl, R 3D10 -substituted or unsubstituted aryl, and R 3D10 -substituted or unsubstituted heteroaryl, and

R 3D8 is a member selected from halogen, —OH, —COOH, —CF 3 , —NH 2 , —SH, R 3D9 -substituted or unsubstituted (C 1 -C 10 )alkyl, R 3D9 -substituted or unsubstituted 2-10 membered heteroalkyl, R 3D9 -substituted or unsubstituted (C 3 -C 8 )cycloalkyl, R 3D9 -substituted or unsubstituted 3-8 membered heterocycloalkyl, R 3D10 -substituted or unsubstituted aryl, and R 3D10 -substituted or unsubstituted heteroaryl,

R 3D9 is a member selected from halogen, oxo, —OH, —COOH, —CF 3 , —NH 2 , —SH, unsubstituted (C 1 -C 10 )alkyl, unsubstituted 2-10 membered heteroalkyl, unsubstituted (C 3 -C 8 )cycloalkyl, unsubstituted 3-8 membered heterocycloalkyl, unsubstituted aryl, and unsubstituted heteroaryl, and

R 3D10 is a member selected from halogen, —OH, —COOH, —CF 3 , —NH 2 , —SH, unsubstituted (C 1 -C 10 )alkyl, unsubstituted 2-10 membered heteroalkyl, unsubstituted (C 3 -C 8 )cycloalkyl, unsubstituted 3-8 membered heterocycloalkyl, unsubstituted aryl, and unsubstituted heteroaryl.

5. The compound of claim 4 , wherein R 3 has the formula:

wherein

R 3D is a member selected from hydrogen, R 3D7 -substituted (C 1 -C 5 )alkyl, R 3D7 -substituted or unsubstituted 2-5 membered heteroalkyl, R 3D7 -substituted (C 5 -C 7 )cycloalkyl, R 3D7 -substituted or unsubstituted 5-7 membered heterocycloalkyl, R 3D8 -substituted aryl, R 3D8 -substituted or unsubstituted heteroaryl, —NR 3D1 R 3D2 , —OR 3D3 , —C(O)NR 3D4 R 3D5 , and —C(O)R 3D6 .

6. The compound of claim 5 , wherein

R 3D is a member selected from —NR 3D1 R 3D2 , —OR 3D3 , —C(O)NR 3D4 R 3D5 , and R 3D7 -substituted or unsubstituted heteroaryl comprising a ring nitrogen, wherein

R 3D1 and R 3D2 are members independently selected from hydrogen, R 3D7 -substituted alkyl, R 3D7 -substituted or unsubstituted heteroalkyl, R 3D7 -substituted or unsubstituted heterocycloalkyl, and R 3D8 -substituted or unsubstituted heteroaryl,

wherein R 3D1 and R 3D2 are optionally joined with the nitrogen to which they are attached to form a R 3D7 -substituted or unsubstituted heterocycloalkyl, or R 3D8 -substituted or unsubstituted heteroaryl, wherein said ring optionally comprises an additional ring heteroatom; and

R 3D3 , R 3D4 and R 3D5 are members independently selected from hydrogen,

R 3D7 -substituted or unsubstituted heteroalkyl comprising a nitrogen heteroatom,

R 3D7 -substituted or unsubstituted heterocycloalkyl comprising a ring nitrogen,

R 3D8 -substituted or unsubstituted heteroaryl comprising a ring nitrogen, and

alkyl substituted with a R 3D9 -substituted or unsubstituted heteroalkyl comprising a nitrogen heteroatom, R 3D9 -substituted or unsubstituted heterocycloalkyl comprising a ring nitrogen, or R 3D10 -substituted or unsubstituted heteroaryl comprising a ring nitrogen,

wherein R 3D4 and R 3D5 are optionally joined with the nitrogen to which they are attached to form a R 3D7 -substituted or unsubstituted heterocycloalkyl, or R 3D8 -substituted or unsubstituted heteroaryl, wherein said ring optionally comprises a heteroatom.

7. The compound of claim 6 , wherein

R 3D1 and R 3D2 , and R 3D4 and R 3D5 are optionally joined with the nitrogen to which they are attached to form a R 3D7 -substituted or unsubstituted heterocycloalkyl comprising an additional heteroatom, or R 3D8 -substituted or unsubstituted heteroaryl comprising an additional heteroatom.

8. The compound of claim 7 , wherein R 3D1 and R 3D2 , and R 3D4 and R 3D5 are optionally joined with the nitrogen to which they are attached to form a R 3D8 -substituted or unsubstituted oxazolyl, imidazolyl, thiazolyl, isooxazolyl, pyrazolyl, isothiazolyl, purinyl, pyradizinyl, pyrimidinyl, pyrazinyl, or quinoxalinyl.

9. The compound of claim 1 , wherein

R 4G is a member independently selected from hydrogen, halogen, —OH, —COOH, —CF 3 , —NH 2 , —SH, R 4G1 -substituted or unsubstituted alkyl, R 4G1 -substituted or unsubstituted heteroalkyl, R 4G1 -substituted or unsubstituted cycloalkyl, R 4G1 -substituted or unsubstituted heterocycloalkyl, R 4G2 -substituted or unsubstituted aryl, and R 4G2 -substituted or unsubstituted heteroaryl, wherein

R 4G1 is a member selected from halogen, oxo, —OH, —COOH, —CF 3 , —NH 2 , —SH, R 4G3- substituted or unsubstituted (C 1 -C 10 )alkyl, R 4G3- substituted or unsubstituted 2-10 membered heteroalkyl, R 4G3- substituted or unsubstituted (C 3 -C 8 )cycloalkyl, R 4G3- substituted or unsubstituted 3-8 membered heterocycloalkyl, R 4G4- substituted or unsubstituted aryl, and R 4G4- substituted or unsubstituted heteroaryl, and

R 4G2 is a member selected from halogen, —OH, —COOH, —CF 3 , —NH 2 , —SH, R 4G3- substituted or unsubstituted (C 1 -C 10 )alkyl, R 4G3- substituted or unsubstituted 2-10 membered heteroalkyl, R 4G3- substituted or unsubstituted (C 3 -C 8 )cycloalkyl, R 4G3- substituted or unsubstituted 3-8 membered heterocycloalkyl, R 4G4- substituted or unsubstituted aryl, and R 4G4- substituted or unsubstituted heteroaryl,

R 4G3 is a member selected from halogen, oxo, —OH, —COOH, —CF 3 , —NH 2 , —SH, unsubstituted (C 1 -C 10 )alkyl, unsubstituted 2-10 membered heteroalkyl, unsubstituted (C 3 -C 8 )cycloalkyl, unsubstituted 3-8 membered heterocycloalkyl, unsubstituted aryl, and unsubstituted heteroaryl, and

R 4G4 is a member selected from halogen, —OH, —COOH, —CF 3 , —NH 2 , —SH, unsubstituted (C 1 -C 10 )alkyl, unsubstituted 2-10 membered heteroalkyl, unsubstituted (C 3 -C 8 )cycloalkyl, unsubstituted 3-8 membered heterocycloalkyl, unsubstituted aryl, and unsubstituted heteroaryl.

10. The compound of claim 9 , wherein A is a member selected from phenyl, pyrazolyl, furanyl, imidazolyl, isoxazolyl, oxadiazolyl, oxazolyl, pyrrolyl, pyridyl, pyrazyl, pyrimidyl, pyridazinyl, thiazolyl, isothioazolyl, triazolyl, thienyl, triazinyl, thiadiazolyl, dioxolanyl, dioxanyl, trioxanyl, tetrahydrothienyl, tetrahydrofuranyl, tetrahydrothiophenyl, tetrahydropyranyl, tetrahydrothiopyranyl, pyrrolidinyl, morpholino, piperidinyl, and piperazinyl.

11. The compound of claim 1 , wherein

R 4G is selected from hydrogen, substituted (C 1 -C 5 )alkyl, substituted or unsubstituted 2-5 membered heteroalkyl, substituted (C 5 -C 7 )cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted aryl, and substituted or unsubstituted heteroaryl;

A is a substituted or unsubstituted ring selected from substituted or unsubstituted 3-7 membered heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; and

R 4I is hydrogen.

12. The compound of claim 1 , wherein R 4G is a branched or unbranched (C 1 -C 10 )alkyl.

13. The compound of claim 1 , wherein X is —S(O) 2 —.

14. The compound of claim 1 , wherein

L 4 is selected from a bond and unsubstituted (C 1 -C 5 )alkylene.

15. The compound of claim 1 wherein

the dashed line b is a bond;

R 4G is a member selected from substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl,

X is —S(O) 2 —;

W is 1;

and

L 4 is a bond.

16. The compound of claim 1 having the formula:

17. The compound of claim 1 having the formula:

18. The compound of claim 1 having the formula:

wherein

R 4G is a member selected from substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;

and

X is a member selected from a bond, —S(O) 2 —, and —S(O) 2 NR 4I —, wherein

R 4I is a member selected from hydrogen, substituted or unsubstituted alkyl, and substituted or unsubstituted heteroalkyl.

19. The compound of claim 1 having the formula:

wherein

R 4A is selected from the group consisting of cycloalkyl, heterocycloalkyl, aryl, and heteroaryl.

20. A compound selected from the group consisting of:

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