Liver X receptor (LXR) modulators for the treatment of dermal diseases, disorders and conditions

1. A compound of Formula (D):

wherein:

X is —N(R 12 )— or —O—;

A and B are each nitrogen, wherein A and B are bonded together to form a five-membered heteroaryl ring;

L 1 is a bond, C 1 -C 6 alkyl, or C 1 -C 6 heteroalkyl;

L 2 is C 1 -C 6 alkyl or C 1 -C 6 heteroalkyl;

R 1 is hydrogen, halogen, —CF 3 , —OR 8 , —N(R 8 ) 2 , —C(═O)R 8 , —C(═O)OR 8 , —C(═O)N(R 8 ) 2 , —C(═N—OH)R 8 , —C(═S)N(R 8 ) 2 , —C(═CH 2 )CH 3 , or —C(═O)OCH 2 SCH 3 ;

R 2 is —C(═O)OR 9 , —C(═O)N(R 9 ) 2 , —NR 10 C(═O)R 9 , —C(═N—OH)R 9 , —C(═S)N(R 9 ) 2 , or —C(═O)OCH 2 SCH 3 ;

R 3 is hydrogen, halogen, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;

R 4 is aryl or heteroaryl; wherein aryl or heteroaryl is substituted with at least one R 11 ;

each R 8 , each R 9 , and each R 10 are each independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, —C 1 -C 6 alkyl-aryl, aryl, or heteroaryl;

R 11 is independently halogen, nitro, —OR 10 , —N(R 10 ) 2 , —CN, —C(═O)R 10 , —C(═O)OR 10 , —C(═O)N(R 10 ) 2 , —NR 10 C(═O)R 10 , NR 10 SO 2 R 10 , —SOR 10 , —SO 2 R 10 , —SO 2 N(R 10 ) 2 , —C(═O)OCH 2 SCH 3 , C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 6 haloalkyl, C 1 -C 6 heteroalkyl, —C 1 -C 6 alkyl-aryl, optionally substituted aryl, or optionally substituted heteroaryl;

R 12 is hydrogen or C 1 -C 6 alkyl;

or a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof.

2. The compound of claim 1 , or a pharmaceutically acceptable or a pharmaceutically acceptable solvate thereof, wherein X is —N(R 12 )—.

3. The compound of claim 1 , or a pharmaceutically acceptable or a pharmaceutically acceptable solvate thereof, wherein R 1 is —CF 3 .

4. The compound of claim 1 , or a pharmaceutically acceptable or a pharmaceutically acceptable solvate thereof, wherein R 2 is —C(═O)OR 9 .

5. The compound of claim 1 , or a pharmaceutically acceptable or a pharmaceutically acceptable solvate thereof, wherein L 1 is a bond and L 2 is C 1 -C 6 alkyl.

6. The compound of claim 1 , or a pharmaceutically acceptable or a pharmaceutically acceptable solvate thereof, wherein R 4 is phenyl substituted with one R 11 .

7. The compound of claim 1 , or a pharmaceutically acceptable or a pharmaceutically acceptable solvate thereof, wherein R 4 is phenyl substituted with two R 11 .

8. The compound of claim 1 , or a pharmaceutically acceptable or a pharmaceutically acceptable solvate thereof, wherein R 11 is —SO 2 R 10 .

9. The compound of claim 1 , or a pharmaceutically acceptable or a pharmaceutically acceptable solvate thereof, wherein R 11 is —SO 2 N(R 10 ) 2 .

10. The compound of claim 1 , or a pharmaceutically acceptable or a pharmaceutically acceptable solvate thereof, wherein X is —N(R 12 )—, L 1 is a bond, R 1 is —CF 3 , L 2 is C 1 -C 6 alkyl, R 2 is C(═O)OR 9 , R 9 is C 1 -C 6 alkyl, R 4 is phenyl substituted with one R 11 , R 11 is —SO 2 R 10 , and R 10 is C 1 -C 6 alkyl.

11. The compound of claim 1 , or a pharmaceutically acceptable or a pharmaceutically acceptable solvate thereof, wherein X is —N(R 12 )—, L 1 is a bond, R 1 is —CF 3 , L 2 is C 1 -C 6 alkyl, R 2 is C(═O)OR 9 , R 9 is C 1 -C 6 heteroalkyl, R 4 is phenyl substituted with one R 11 , R 11 is —SO 2 R 10 , and R 10 is C 1 -C 6 alkyl.

12. The compound of claim 1 , or a pharmaceutically acceptable or a pharmaceutically acceptable solvate thereof, wherein R 3 is hydrogen or halogen.

13. The compound of claim 1 , or a pharmaceutically acceptable or a pharmaceutically acceptable solvate thereof, wherein X is —O—.

14. The compound of claim 1 , or a pharmaceutically acceptable or a pharmaceutically acceptable solvate thereof, wherein R 1 is —CF 3 .

15. The compound of claim 1 , or a pharmaceutically acceptable or a pharmaceutically acceptable solvate thereof, wherein R 2 is —C(═O)OR 9 .

16. The compound of claim 1 , or a pharmaceutically acceptable or a pharmaceutically acceptable solvate thereof, wherein L 1 is a bond and L 2 is C 1 -C 6 alkyl.

17. The compound of claim 1 , or a pharmaceutically acceptable or a pharmaceutically acceptable solvate thereof, wherein R 4 is phenyl substituted with one R 11 .

18. The compound of claim 1 , or a pharmaceutically acceptable or a pharmaceutically acceptable solvate thereof, wherein R 4 is phenyl substituted with two R 11 .

19. The compound of claim 1 , or a pharmaceutically acceptable or a pharmaceutically acceptable solvate thereof, wherein R 11 is —SO 2 R 10 .

20. The compound of claim 1 , or a pharmaceutically acceptable or a pharmaceutically acceptable solvate thereof, wherein R 11 is C 1 -C 6 heteroalkyl.

21. The compound of claim 1 , or a pharmaceutically acceptable or a pharmaceutically acceptable solvate thereof, wherein X is —O—, L 1 is a bond, R 1 is —CF 3 , L 2 is C 1 -C 6 alkyl, R 2 is C(═O)OR 9 , R 9 is C 1 -C 6 alkyl, R 4 is phenyl substituted with one R 11 , R 11 is —SO 2 R 10 , and R 10 is C 1 -C 6 alkyl.

22. The compound of claim 1 , or a pharmaceutically acceptable or a pharmaceutically acceptable solvate thereof, wherein R 3 is hydrogen or halogen.

23. The compound of claim 1 , or a pharmaceutically acceptable or a pharmaceutically acceptable solvate thereof, selected from:

or a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof.

24. A pharmaceutical composition comprising a pharmaceutically acceptable diluent, excipient or binder, and a compound of claim 1 , or a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof.

25. A method of treating a disease, disorder or condition selected from selected from skin aging, scarring, psoriasis, dermatitis, eczema, urticaria, rosacea, burns, acne, ichthyoses, vitiligo, metastatic melanoma, and xerosis in a mammal, comprising administering to the mammal a compound of claim 1 , or a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof.

26. The method of claim 25 , wherein the disease is dermatitis.

27. The method of claim 26 , wherein the dermatitis is atopic dermatitis.

28. The method of claim 26 , wherein the dermatitis is dermatitis resulting from allergic and irritant contact.