Pyrido[4,3-B]indoles and methods of use

1. A compound of the formula (A):

wherein:

R 1 is H, hydroxyl, nitro, cyano, halo, substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 2 -C 8 alkenyl, substituted or unsubstituted C 2 -C 8 alkynyl, perhaloalkyl, acyl, acyloxy, carbonylalkoxy, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, C 1 -C 8 perhaloalkoxy, alkoxy, aryloxy, carboxyl, thiol, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl or carbonylalkylenealkoxy;

R 2 is H, hydroxyl, nitro, cyano, halo, C 1 -C 8 perhaloalkyl, substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 2 -C 8 alkenyl, substituted or unsubstituted C 2 -C 8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, C 1 -C 8 perhaloalkoxy, C 1 -C 8 alkoxy, aryloxy, carboxyl, carbonylalkoxy, thiol, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl, carbonylalkylenealkoxy, alkylsulfonylamino or acyl;

X is OH, H, C 1 -C 8 unsubstituted alkyl or is taken together with Y to form a cyclic moiety of the formula —OCH 2 CH 2 O—;

Y is halo, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, C 1 -C 8 alkyl substituted with a carbonylalkoxy, carboxyl or acylamino moiety or is taken together with X to form a cyclic moiety of the formula —OCH 2 CH 2 O—; and

R 3 is a substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkenyl or substituted or a unsubstituted heterocyclyl

or a salt or solvate thereof.

2. The compound of claim 1 , or a salt or solvate thereof, wherein X is OH and Y is an unsubstituted aryl.

3. The compound of claim 2 , or a salt or solvate thereof, wherein the compound is of the formula (I):

and wherein R 1 , R 2 and R 3 are as defined for formula (A).

4. The compound of claim 3 , or a salt or solvate thereof, wherein R 1 and R 2 are independently an unsubstituted C 1 -C 8 alkyl or halo, and R 3 is a substituted aryl or unsubstituted heteroaryl.

5. The compound of claim 4 , wherein R 1 is methyl.

6. The compound of claim 4 , wherein R 2 is methyl or chloro.

7. The compound of claim 4 , wherein R 3 is a substituted phenyl, or unsubstituted pyridyl, pyrimidinyl, pyrazinyl, imidazolyl, oxazolyl, oxadiazolyl, furanyl, pyrrolyl or thiophenyl group.

8. The compound of claim 1 , or a salt or solvate thereof, where the compound is of the formula (II):

and wherein R 1 , R 2 and R 3 are as defined for formula (A).

9. The compound of claim 8 , or a salt or solvate thereof, wherein R 1 is an unsubstituted C 1 -C 8 alkyl, R 2 is H, an unsubstituted C 1 -C 8 alkyl or halo, and R 3 is a substituted or unsubstituted aryl or a substituted or unsubstituted heteroaryl.

10. The compound of claim 9 , wherein R 1 is methyl.

11. The compound of claim 9 , wherein R 2 is methyl or chloro.

12. The compound of claim 9 , wherein R 3 is a substituted or unsubstituted phenyl, pyridyl, pyrimidinyl, pyrazinyl, imidazolyl, oxazolyl, oxadiazolyl, furanyl, pyrrolyl or thiophenyl group.

13. The compound of claim 1 , or a salt or solvate thereof, wherein X is H and Y is a C 1 -C 8 alkyl substituted with a carbonylalkoxy, carboxyl or acylamino moiety.

14. The compound of claim 13 , or a salt or solvate thereof, wherein Y is a moiety selected from the structures:

where R 4 is a C 1 -C 8 unsubstituted alkyl.

15. The compound of claim 14 , or a salt or solvate thereof, wherein the compound is of the formula (III):

and wherein R 1 , R 2 and R 3 are as defined for formula (A) and R 4 is an unsubstituted C 1 -C 8 alkyl.

16. The compound of claim 15 , or a salt or solvate thereof, wherein R 1 is an unsubstituted C 1 -C 8 alkyl, R 2 is an unsubstituted C 1 -C 8 alkyl or halo, and R 3 is a substituted aryl or a substituted or unsubstituted heteroaryl.

17. The compound of claim 16 , wherein R 1 is methyl.

18. The compound of claim 16 , wherein R 2 is methyl or chloro.

19. The compound of claim 16 , wherein R 3 is a substituted phenyl, or a substituted or unsubstituted pyridyl, pyrimidinyl, pyrazinyl, imidazolyl, oxazolyl, oxadiazolyl, furanyl, pyrrolyl or thiophenyl group.

20. The compound of claim 14 , or a salt or solvate thereof, wherein the compound is of the formula (IV):

and wherein R 1 , R 2 and R 3 are as defined for formula (A).

21. The compound of claim 20 , or a salt or solvate thereof, wherein R 1 is an unsubstituted C 1 -C 8 alkyl, R 2 is an unsubstituted C 1 -C 8 alkyl or halo, and R 3 is a substituted aryl or a substituted or unsubstituted heteroaryl.

22. The compound of claim 21 , wherein R 1 is methyl.

23. The compound of claim 21 , wherein R 2 is methyl or chloro.

24. The compound of claim 21 , wherein R 3 is a substituted phenyl, or a substituted or unsubstituted pyridyl, pyrimidinyl, pyrazinyl, imidazolyl, oxazolyl, oxadiazolyl, furanyl, pyrrolyl or thiophenyl group.

25. The compound of claim 14 , or a salt or solvate thereof, wherein the compound is of the formula (V):

and wherein R 1 , R 2 and R 3 are as defined for formula (A).

26. The compound of claim 25 , or a salt or solvate thereof, wherein R 1 is an unsubstituted C 1 -C 8 alkyl, R 2 is an unsubstituted C 1 -C 8 alkyl or halo, and R 3 is a substituted aryl or a substituted or unsubstituted heteroaryl.

27. The compound of claim 26 , wherein R 1 is methyl.

28. The compound of claim 26 , wherein R 2 is methyl or chloro.

29. The compound of claim 26 , wherein R 3 is a substituted phenyl, or a substituted or unsubstituted pyridyl, pyrimidinyl, pyrazinyl, imidazolyl, oxazolyl, oxadiazolyl, furanyl, pyrrolyl or thiophenyl group.

30. The compound of claim 1 , or a salt or solvate thereof, wherein X is an H or an unsubstituted C 1 -C 8 alkyl and Y is halo.

31. The compound of claim 30 , or a salt or solvate thereof, wherein the compound is of the formula (VI):

and wherein R 1 , R 2 and R 3 are as defined for formula (A).

32. The compound of claim 31 , wherein R 1 is an unsubstituted C 1 -C 8 alkyl, R 2 is an unsubstituted C 1 -C 8 alkyl or halo, and R 3 is an unsubstituted heteroaryl.

33. The compound of claim 32 , wherein R 1 is methyl.

34. The compound of claim 32 , wherein R 2 is methyl or chloro.

35. The compound of claim 32 , wherein R 3 is an unsubstituted pyridyl, pyrimidinyl, pyrazinyl, imidazolyl, oxazolyl, oxadiazolyl, furanyl, pyrrolyl or thiophenyl group.

36. The compound of claim 30 , or a salt or solvate thereof, wherein the compound is of the formula (VII):

and wherein R 1 , R 2 and R 3 are as defined for formula (A).

37. The compound of claim 30 wherein R 1 and R 2 are independently an unsubstituted C 1 -C 8 alkyl and R 3 is an unsubstituted heteroaryl.

38. The compound of claim 37 , wherein R 1 is methyl.

39. The compound of claim 37 , wherein R 2 is methyl.

40. The compound of claim 37 , wherein R 3 is an unsubstituted pyridyl, pyrimidinyl, pyrazinyl, imidazolyl, oxazolyl, oxadiazolyl, furanyl, pyrrolyl or thiophenyl group.

41. A compound selected from the group consisting of:

2-(2,8-Dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-1-(4-fluorophenyl)-1-phenylethanol;

2,8-Dimethyl-5-((2-phenyl-1,3-dioxolan-2-yl)methyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole;

5-((2-(4-Fluorophenyl)-1,3-dioxolan-2-yl)methyl)-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole;

8-Chloro-5-((2-(4-fluorophenyl)-1,3-dioxolan-2-yl)methyl)-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole;

8-Chloro-5-((2-(4-chlorophenyl)-1,3-dioxolan-2-yl)methyl)-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole;

Ethyl 4-(2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-3-(4-fluorophenyl)butanoate;

4-(2,8-Dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-3-(4-fluorophenyl)butanoic acid;

4-(2,8-Dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-3-(4-fluorophenyl)-N-methylbutanamide;

5-(2-Fluoro-2-(pyridin-4-yl)propyl)-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole;

8-Chloro-5-(2-fluoro-2-(pyridin-4-yl)propyl)-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole;

2-(2,8-Dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-1-phenyl-1-(pyridin-4-yl)EtOH;

2-Methyl-5-((2-(pyridin-4-yl)-1,3-dioxolan-2-yl)methyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole;

2,8-Dimethyl-5-((2-(pyridin-3-yl)-1,3-dioxolan-2-yl)methyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole;

5-((2-(2,4-Difluorophenyl)-1,3-dioxolan-2-yl)methyl)-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole;

2,8-Dimethyl-5-((2-(pyrimidin-4-yl)-1,3-dioxolan-2-yl)methyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole;

8-Chloro-5-((2-(2-chlorophenyl)-1,3-dioxolan-2-yl)methyl)-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole;

8-Chloro-2-methyl-5-((2-(2-methylpyridin-4-yl)-1,3-dioxolan-2-yl)methyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole;

8-Chloro-5-((2-(2-fluorophenyl)-1,3-dioxolan-2-yl)methyl)-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole;

8-Chloro-2-methyl-5-((2-(6-methylpyridin-3-yl)-1,3-dioxolan-2-yl)methyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole;

8-Chloro-2-methyl-5-((2-(3-methylpyridin-4-yl)-1,3-dioxolan-2-yl)methyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole;

8-Chloro-5-((2-(4-methoxyphenyl)-1,3-dioxolan-2-yl)methyl)-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole;

Isopropyl 4-(8-chloro-2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-3-(4-methoxyphenyl)butanoate;

Isopropyl 4-(8-chloro-2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-3-(4-chlorophenyl)butanoate;

Isopropyl 4-(8-chloro-2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-3-(6-methylpyridin-3-yl)butanoate;

tert-Butyl 4-(2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-3-(4-fluorophenyl)butanoate;

Methyl 3-(2,4-difluorophenyl)-4-(2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)butanoate;

Ethyl 4-(8-chloro-2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-3-(3-methylpyridin-4-yl)butanoate;

Ethyl 4-(2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-3-(pyridin-4-yl)butanoate;

Ethyl 4-(2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-3-(pyridin-3-yl)butanoate;

Ethyl 4-(8-chloro-2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-3-(pyrimidin-4-yl)butanoate;

Ethyl 4-(2-ethyl-8-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-3-(2-methylpyridin-4-yl)butanoate;

4-(2,8-Dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-3-(pyridin-4-yl)butanoic acid;

4-(2,8-Dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-3-(pyridin-3-yl)butanoic acid;

4-(8-Chloro-2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-3-(pyrimidin-4-yl)butanoic acid;

4-(2-Ethyl-8-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-3-(2-methylpyridin-4-yl)butanoic acid;

4-(8-Chloro-2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-3-(6-methylpyridin-3-yl)butanoic acid;

4-(2,8-Dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-3-(2-fluorophenyl)butanoic acid;

3-(2,4-Difluorophenyl)-4-(2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)butanoic acid;

4-(8-Chloro-2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-3-(3-methylpyridin-4-yl)butanoic acid;

4-(8-Chloro-2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-3-(4-methoxyphenyl)butanoic acid;

4-(8-Chloro-2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-3-(4-chlorophenyl)butanoic acid;

4-(2,8-Dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-N-methyl-3-(pyridin-4-yl)butanamide;

4-(2,8-Dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-N-methyl-3-(pyridin-3-yl)butanamide;

4-(8-Chloro-2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-N-methyl-3-(pyrimidin-4-yl)butanamide;

4-(2,8-Dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-N-methyl-3-(2-methylpyridin-4-yl)butanamide;

4-(8-Chloro-2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-N-methyl-3-(6-methylpyridin-3-yl)butanamide;

4-(2,8-Dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-3-(2-fluorophenyl)-N-methylbutanamide;

3-(2,4-Difluorophenyl)-4-(2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-N-methylbutanamide;

4-(8-Chloro-2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-N-methyl-3-(3-methylpyridin-4-yl)butanamide;

4-(8-Chloro-2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-3-(4-methoxyphenyl)-N-methylbutanamide;

4-(8-Chloro-2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-3-(4-chlorophenyl)-N-methylbutanamide;

5-(2-Fluoro-2-(4-fluorophenyl)propyl)-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole;

8-Chloro-5-(2-(2,4-difluorophenyl)-2-fluoropropyl)-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole;

5-(2-(4-Chlorophenyl)-2-fluoropropyl)-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole;

8-Chloro-5-(2-fluoro-2-(pyridin-3-yl)propyl)-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole;

2-Ethyl-5-(2-fluoro-2-(pyridin-3-yl)propyl)-8-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole;

5-(2-Fluoro-2-(pyrimidin-4-yl)propyl)-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole;

8-Chloro-5-(2-fluoro-2-(6-methylpyridin-3-yl)propyl)-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole;

5-(2-Fluoro-2-(2-methylpyridin-4-yl)propyl)-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole;

2-Cyclopropyl-5-(2-fluoro-2-(4-methoxyphenyl)propyl)-8-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole;

8-Chloro-5-(2-fluoro-2-(3-methylpyridin-4-yl)propyl)-2-isopropyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole; and

5-(2-Fluoro-2-(pyridin-4-yl)ethyl)-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole,

or a pharmaceutically acceptable salt thereof.

42. A method of modulating a histamine receptor in an individual comprising administering to an individual in need thereof a compound according to claim 1 or 41 .

43. A pharmaceutical composition comprising (a) a compound of claim 1 or 41 or a pharmaceutically acceptable salt thereof, and (b) a pharmaceutically acceptable carrier.

44. A kit comprising a compound according to claim 1 or 41 and instructions for use.