2,3,4,5-tetrahydro-1H-pyrido[4,3-B]indole compounds and methods of use thereof

1. A compound of the Formula (E):

or a salt thereof, 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;

each R 2a and R 2b is independently H, substituted or unsubstituted C 1 -C 8 alkyl, halo, cyano, hydroxyl, alkoxy, nitro or R 2a and R 2b are taken together with the carbon to which they are attached to form a cycloalkyl moiety or a carbonyl moiety;

each R 3a and R 3b is independently H, substituted or unsubstituted C 1 -C 8 alkyl, halo, cyano hydroxyl, alkoxy, nitro or R 3a and R 3b are taken together with the carbon to which they are attached to form a cycloalkyl moiety or a carbonyl moiety;

each X 7 , X 8 , X 9 and X 10 is independently CR 4 ;

m and q are independently 0 or 1;

n is 1;

each R 4 is independently 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, 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;

each R 8a , R 8b , R 8c , R 8d , R 8e and R 8f is independently H, hydroxyl, substituted or unsubstituted alkyl or is taken together with the carbon to which it is attached and a geminal R 8(a-f) to form a cycloalkyl moiety;

each R 10a and R 10b is independently H, substituted or unsubstituted C 1 -C 8 alkyl, halo, hydroxyl, alkoxyl or R 10a and R 10b are taken together with the carbon to which they are attached to form a cycloalkyl moiety or a carbonyl moiety; and

Q is acyclic or cyclic acylamino, acyloxy, aminoacyl, or aminocarbonylalkoxy;

provided that: Q is cyclic acylamino only when each of m, n and q is 1, and (ii) the compound is other than a compound selected from the group consisting of compounds: 2H-Pyrido[4,3-b]indole-2-carboxylic acid, 5-[2-(dimethylamino)-2-oxoethyl]-1,3,4,5-tetrahydro-8-[(4-methyl-1-piperidinyl)carbonyl]-, 1,1-dimethylethyl ester (Compound No. 1x); 5H-Pyrido[4,3-b]indole-5-acetamide, 1,2,3,4-tetrahydro-N,N-dimethyl-8-[(4-methyl-1-piperidinyl)carbonyl]- (Compound No. 2x); 5H-Pyrido[4,3-b]indole-5-acetamide, 2-cyclobutyl-1,2,3,4-tetrahydro-N,N-dimethyl-8-[(4-methyl-1-piperidinyl)carbonyl]- (Compound No. 3x); 5H-Pyrido[4,3-b]indole-5-acetamide, 2-cyclohexyl-1,2,3,4-tetrahydro-N,N-dimethyl-8-[(4-methyl-1-piperidinyl)carbonyl] (Compound No. 4x); 5H-Pyrido[4,3-b]indole-5-acetamide, 2-cyclopentyl-1,2,3,4-tetrahydro-N,N-dimethyl-8-[(4-methyl-1-piperidinyl)carbonyl]- (Compound No. 5x); 5H-Pyrido[4,3-b]indole-5-acetamide, 8-formyl-1,2,3,4-tetrahydro-2-(1-methylethyl)- (Compound No. 6x); 5H-Pyrido[4,3-b]indole-5-acetamide, 1,2,3,4-tetrahydro-2-(1-methylethyl)- (Compound No. 11x); 5H-Pyrido[4,3-b]indole-5-acetamide, 1,2,3,4-tetrahydro-2,8-bis(1-methylethyl)- (Compound No. 12x); 5H-Pyrido[4,3-b]indole-5-acetamide, 1,2,3,4-tetrahydro-8-methyl-2-(1-methylethyl)- (Compound No. 13x); 5H-Pyrido[4,3-b]indole-5-acetamide, N-cyclohexyl-1,2,3,4-tetrahydro-2-(1-methylethyl)-(Compound No. 14x); 5H-Pyrido[4,3-b]indole-5-acetamide, N-cyclopentyl-1,2,3,4-tetrahydro-2-(1-methylethyl)- (Compound No. 15x); and 5H-Pyrido[4,3-b]indole-5-propanamide, 1,2,3,4-tetrahydro-2-methyl- (Compound No. 63x); and salts thereof.

2. The compound of claim 1 wherein the compound is selected from the group consisting of compounds:

or a salt thereof.

3. The compound of claim 1 , or a salt thereof, wherein each X 7 , X 8 and X 10 is CR 4 where R 4 is H, X 9 is CR 4 where R 4 is chloro, R 1 is methyl, each R 2a , R 2b , R 3a , R 3b , R 10a and R 10b is H, each R 8a , R 8b , R 8c , R 8d , R 8e and R 8f is H when present and Q is acyclic acylamino or aminoacyl.

4. The compound of claim 1 , or a salt thereof, wherein each X 7 , X 8 and X 10 is CR 4 where R 4 is H, X 9 is CR 4 where R 4 is methyl, R 1 is methyl, each R 2a , R 2b , R 3a , R 3b , R 10a and R 10b is H, each R 8a , R 8b , R 8c , R 8d , R 8e and R 8f is H when present and Q is acyclic acylamino or aminoacyl.

5. The compound of claim 1 , or a salt thereof, wherein each X 7 , X 8 and X 10 is CR 4 where R 4 is H, X 9 is CR 4 where R 4 is chloro or methyl, R 1 is methyl, each R 2a , R 2b , R 3a , R 3b , R 10a and R 10b is H, each R 8a , R 8b , R 8c , R 8d , R 8e and R 8f is H when present and Q is acylamino of the formula —C(O)NHR′ where R′ is unsubstituted or substituted alkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl or unsubstituted or substituted heterocyclyl.

6. The compound of claim 1 , or a salt thereof, wherein each X 7 , X 8 and X 10 is CR 4 where R 4 is H, X 9 is CR 4 where R 4 is methyl, R 1 is methyl, each R 2a , R 2b , R 3a , R 3b , R 10a and R 10b is H, each R 8a , R 8b , R 8c , R 8d , R 8e and R 8f is H when present and Q is of the formula —NHC(O)R′ where R′ is alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, alkoxy or substituted alkoxy.

7. A compound of the formula (Vf):

wherein:

R 1 is methyl;

R 4 is chloro or methyl;

m and q are independently 0 or 1;

each R 8a , R 8b , R 8c , R 8d , R 8e and R 8f is independently H, hydroxyl, substituted or unsubstituted alkyl or is taken together with the carbon to which it is attached and a geminal R 8(a-f) to form a cycloalkyl moiety; and

Q is acyclic or cyclic acylamino, acyloxy, aminoacyl or aminocarbonylalkoxy; or a salt thereof.

8. The compound of claim 7 , or a salt thereof, wherein R 1 is methyl and R 4 is chloro.

9. The compound of claim 7 , or a salt thereof, wherein R 1 and R 4 are methyl and Q is acyclic acylamino, acyloxy, aminoacyl or aminocarbonylalkoxy.

10. The compound of claim 1 , or a salt thereof, wherein the compound modulates at least one of the following receptors: adrenergic receptor, serotonin receptor, dopamine receptor and histamine receptor.

11. A pharmaceutical composition comprising a compound according to any one of claims 1 , 2 and 7 , or a salt thereof, and a pharmaceutically acceptable carrier.

12. The compound of claim 1 , or a salt thereof, wherein X 9 is CR 4 where R 4 is halo or alkyl.

13. The compound of claim 1 , or a salt thereof, wherein X 9 is CR 4 where R 4 is chloro or methyl.

14. The compound of claim 1 , or a salt thereof, wherein each X 7 , X 8 and X 10 is CR 4 where R 4 is H.

15. The compound of claim 1 , or a salt thereof, wherein each of R 2a , R 2b , R 3a , R 3b , R 10a and R 10b is H.

16. The compound of claim 1 , or a salt thereof, wherein R 1 is methyl.

17. The compound of claim 1 , or a salt thereof, wherein at least one of m and q is 1.

18. The compound of claim 1 , or a salt thereof, wherein q is 0 and m is 1.

19. The compound of claim 1 , or a salt thereof, wherein each R 8a , R 8b , R 8c , R 8d , R 8e and R 8 , when present, is H.

20. The compound of claim 1 , or a salt thereof, wherein Q is an acylamino of the formula —C(O)NHR′ where R′ is unsubstituted or substituted alkyl, substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl or unsubstituted or substituted heterocyclyl.

21. The compound of claim 1 , or a salt thereof, wherein Q is of the formula —NHC(O)R′ where R′ is alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, alkoxy or substituted alkoxy.

22. A method of treating a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder or a neuronal disorder in an individual comprising administering to an individual in need thereof an effective amount of a compound of claim 1 , or a salt thereof.

23. A kit comprising a compound according to claim 1 and instructions for use in the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder or a neuronal disorder.