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

1. A compound of the formula (A):

wherein:

R 1 , R 2 , R 3 and R 4 are independently H, halo, C 1 -C 8 unsubstituted alkyl or C 1 -C 8 unsubstituted alkoxy, provided that R 3 is other than methyl or chloro when R 1 , R 2 and R 4 are each H and X is OH and Y is methyl;

R 5 is unsubstituted C 1 -C 8 alkyl or a C 1 -C 8 alkyl substituted with a perhaloalkyl moiety;

R 6 is H or an unsubstituted C 1 -C 8 alkyl;

X is OH, C 1 -C 8 alkyl or is taken together with Y to form a cyclopropyl moiety; and

Y is H, C 1 -C 8 alkyl or is taken together with X to form a cyclopropyl moiety,

or a salt thereof.

2. The compound of claim 1 or a salt thereof, wherein R 5 is methyl, ethyl, cyclopropyl, trifluoroethyl, isopropyl, tert-butyl, sec-butyl, 2-methylbutyl, cyclobutyl, cyclopentyl, or cyclohexyl.

3. The compound of claim 2 or a salt thereof, wherein R 5 is methyl.

4. The compound of claim 1 or a salt thereof, wherein R 3 is halo or C 1 -C 8 unsubstituted alkyl.

5. The compound of claim 4 or a salt thereof, wherein R 3 is chloro or methyl.

6. The compound of claim 1 or a salt thereof, wherein X is OH and Y is C 1 -C 8 alkyl.

7. The compound of claim 6 or a salt thereof, wherein Y is methyl.

8. A compound of the formula (B):

wherein:

R 7 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, 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; and

Z is H, halo or C 1 -C 8 alkyl,

or a salt thereof.

9. The compound of claim 8 or a salt thereof, wherein R 7 is halo or C 1 -C 8 unsubstituted alkyl.

10. The compound of claim 9 or a salt thereof, wherein R 7 is chloro or methyl.

11. The compound of claim 8 or a salt thereof, wherein Z is H or halo.

12. A compound of the formula (C1):

wherein:

R 1 , R 2 , R 3 and R 4 are independently H, halo, C 1 -C 8 unsubstituted alkyl or C 1 -C 8 unsubstituted alkoxy;

R 8 is a substituted or unsubstituted aryl or a substituted or unsubstituted heteroaryl; and

X is a C 4 -C 6 unsubstituted alkyl,

or a salt thereof.

13. The compound of claim 12 or a salt thereof, wherein R 3 is halo or C 1 -C 8 unsubstituted alkyl.

14. The compound of claim 13 or a salt thereof, wherein R 3 is chloro or methyl.

15. The compound of claim 14 or a salt thereof, wherein R 8 is a substituted or unsubstituted pyridyl, phenyl, pyrimidinyl, pyrazinyl, imidazolyl, oxazolyl, oxadiazolyl, furanyl, pyrrolyl or thiophenyl group.

16. A compound of the formula (D1):

wherein:

R 1 , R 2 , R 3 and R 4 are independently H, halo, C 1 -C 8 unsubstituted alkyl or C 1 -C 8 unsubstituted alkoxy;

and

V is a halo,

or a salt thereof.

17. The compound of claim 16 or a salt thereof, wherein R 3 is halo or C 1 -C 8 unsubstituted alkyl.

18. The compound of claim 17 or a salt thereof, wherein R 3 is chloro or methyl.

19. A compound of the formula (E1):

wherein:

R 1 , R 2 , and R 4 are independently H, halo, C 1 -C 8 unsubstituted alkyl or C 1 -C 8 unsubstituted alkoxy;

R 8 is 6-pyrimidyl, 3-methyl-4-pyridyl or a phenyl substituted either: (i) with at least one alkoxy or hydroxyl group or (ii) with at least two halo groups; and

R 9 is an unsubstituted C 1 -C 3 alkyl,

or a salt thereof.

20. The compound of claim 19 or a salt thereof, wherein R 9 is methyl.

21. A compound of the formula (F1):

wherein:

R 1 , R 2 , R 3 and R 4 are independently H, halo, C 1 -C 8 unsubstituted alkyl or C 1 -C 8 unsubstituted alkoxy;

R 5 is

where T is 3 or 4

X is H or OH;

Y is H or C 1 -C 8 alkyl; and

R 8 is a substituted or unsubstituted heteroaryl,

or a salt thereof.

22. The compound of claim 21 or a salt thereof, wherein R 3 is halo or C 1 -C 8 unsubstituted alkyl.

23. The compound of claim 22 or a salt thereof, wherein R 3 is chloro or methyl.

24. The compound of claim 21 or a salt thereof, wherein X is OH and Y is C 1 -C 8 alkyl.

25. The compound of claim 24 or a salt thereof, wherein Y is methyl.

26. The compound of claim 21 or a salt thereof, wherein R 8 is a substituted or unsubstituted pyridyl, phenyl, pyrimidinyl, pyrazinyl, imidazolyl, oxazolyl, oxadiazolyl, furanyl, pyrrolyl or thiophenyl group.

27. A compound of the formula (G):

wherein:

R 1 , R 2 and R 4 are independently H, halo, C 1 -C 8 unsubstituted alkyl or C 1 -C 8 unsubstituted alkoxy;

R 3 is methyl or chloro, provided that R 3 is methyl when R 8 is a substituted heteroaryl;

X is H or OH;

Y is H or C 1 -C 8 alkyl; and

R 8 is a substituted or unsubstituted heteroaryl,

or a salt thereof.

28. The compound of claim 27 or a salt thereof, wherein X is OH and Y is C 1 -C 8 alkyl.

29. The compound of claim 28 or a salt thereof, wherein Y is methyl.

30. A compound selected from the group consisting of:

Comp. #

Compound Structure

1-1

1-2

1-3

1-4

1-5

1-6

1-7

1-8

1-9

1-10

1-11

1-12

1-13

1-14

1-15

1-16

1-17

1-18

1-19

1-20

1-21

1-22

1-23

1-24

1-25

1-26

1-27

1-28

1-29

1-30

1-31

1-32

1-33

1-34

1-35

1-36

1-37

1-38

1-39

1-40

1-41

1-42

1-43

1-44

1-45

1-46

1-47

1-48

1-49

1-50

1-51

1-52

1-53

1-54

1-56

1-57

1-58

1-59

or a pharmaceutically acceptable salt thereof.

31. A method of modulating a histamine receptor in an individual comprising administering to an individual in need thereof a compound according to any one of claims 1 , 8 , 12 , 16 , 19 , 21 , 27 , and 30 , or a pharmaceutically acceptable salt thereof.

32. A pharmaceutical composition comprising (a) a compound of any one of claims 1 , 8 , 12 , 16 , 19 , 21 , 27 , and 30 , or a pharmaceutically acceptable salt thereof, and (b) a pharmaceutically acceptable carrier.

33. A kit comprising a compound according to any one of claims 1 , 8 , 12 , 16 , 19 , 21 , 27 , and 30 , or a pharmaceutically acceptable salt thereof, and instructions for use.