AZA-bridged ring-fused indoles and indolines

1. A compound of formula (I),

or a pharmaceutically acceptable salt thereof, wherein

a is a single or double bond;

i is 0;

j is 0;

h is 1, 2, or 3;

m is 1;

n is 0;

X is O, S, S(O), or a bond;

L is —[C(R a )(R b )] p —, —[C(R a )(R b )] q1 —[(CR c )═(CR d )]—[C(R a )(R b )] q2 —,—[C(R a )(R b )] r1 —[C≡C]—[C(R a )(R b )] r2 —, —[C(R a )(R b )] s -cyclopropylene-[C(R a )(R b )] t —, a bond or Y, wherein Y is substituted or unsubstituted monocyclic aryl or substituted or unsubstituted furanyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, 1,3-oxazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrazolyl, pyrrolyl, tetrazolyl, thiadiazolyl, 1,3-thiazolyl, thienyl, triazolyl, or triazinyl; or X and L taken together are a bond;

Q is substituted or unsubstituted monocyclic aryl, substituted or unsubstituted bicyclic aryl, substituted or unsubstituted monocyclic heteroaryl, or substituted or unsubstituted bicyclic heteroaryl;

R 1 is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, —C(O)—C 1 -C 4 alkyl, —C(O)—C 1 -C 4 haloalkyl, —C(O)O-C 1 -C 4 alkyl, or —C(O)O-C 1 -C 4 haloalkyl;

R 2 is hydrogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, or C 2 -C 4 alkynyl, wherein C 1 -C 4 alkyl, and the saturated carbon atoms of C 2 -C 4 alkenyl and C 2 -C 4 alkynyl, can be unsubstituted or substituted by hydroxyl, C 1 -C 8 alkyl, C 1 -C 8 haloalkyl, carboxy, or alkoxycarbonyl;

R 3 is hydrogen, halogen, C 1 -C 5 haloalkyl, C 1 -C 5 alkoxy, C 1 -C 5 haloalkoxy, or cyano;

R a , R b , R c , and R d , are, at each occurrence, independently hydrogen, halogen, C 1 -C 8 alkyl, C 1 -C 8 haloalkyl, carboxy, or alkoxycarbonyl;

p is 1, 2, 3, 4, or 5;

q1 and q2 are independently 0, 1, 2, or 3, provided that the sum of q1 and q2 is 0, 1, 2, or 3;

r1 and r2 are independently 0, 1, 2, or 3, provided that the sum of r1 and r2 is 0, 1, 2, or 3;

s is 0, 1 or 2; and

t is 0 or 1;

wherein Q or Y, when substituted, are independently substituted with 1, 2, 3, 4, or 5 substituents, wherein the substituent is halogen, cyano, C 1 -C 5 haloalkyl, C 1 -C 5 alkyl, C 2 -C 5 alkenyl, C 2 -C 5 alkynyl, hydroxy, C 1 -C 5 alkoxy, —O—C 1 -C 5 haloalkyl, —S—C 1 -C 5 alkyl, —S—C 1 -C 5 haloalkyl, —SO 2 —C 1 -C 5 alkyl, —SO 2 —C 1 -C 5 haloalkyl, C 1 -C 5 cyanoalkyl, or —NO 2 .

2. The compound of claim 1 , wherein the compound of formula (I) has the structure:

wherein R 1 , R 2 , R 3 , X, L, and Q, are as defined in claim 1 .

3. The compound of claim 1 , wherein X is O or a bond and L is —[C(R a )(R b )] p —.

4. The compound of claim 3 , wherein R 2 is hydrogen.

5. The compound of claim 3 , wherein R 2 is C 1 -C 4 alkyl.

6. The compound of claim 3 , wherein R 2 is C 2 -C 4 alkenyl.

7. The compound of claim 3 , wherein R 2 is C 2 -C 4 alkynyl.

8. The compound of claim 1 , wherein X is a bond and L is —[C(R a )(R b )] q1 —[(CR c )═(CR d )]—[C(R a )(R b )] q2 —.

9. The compound of claim 8 , wherein R 2 is hydrogen.

10. The compound of claim 8 , wherein R 2 is C 1 -C 4 alkyl.

11. The compound of claim 8 , wherein R 2 is C 2 -C 4 alkenyl.

12. The compound of claim 8 , wherein R 2 is C 2 -C 4 alkynyl.

13. The compound of claim 1 , wherein X is a bond and L is —[C(R a )(R b )] r1 —[C≡C]—[C(R a )(R b )] r2 —.

14. The compound of claim 13 , wherein R 2 is hydrogen.

15. The compound of claim 13 , wherein R 2 is C 1 -C 4 alkyl.

16. The compound of claim 13 , wherein R 2 is C 2 -C 4 alkenyl.

17. The compound of claim 13 , wherein R 2 is C 2 -C 4 alkynyl.

18. The compound of claim 1 , wherein L is Y.

19. The compound of claim 18 , wherein R 2 is hydrogen.

20. The compound of claim 18 , wherein R 2 is C 1 -C 4 alkyl.

21. The compound of claim 18 , wherein R 2 is C 2 -C 4 alkenyl.

22. The compound of claim 18 , wherein R 2 is C 2 -C 4 alkynyl.

23. The compound of claim 1 , wherein X and L together are a bond.

24. The compound of claim 23 , wherein R 2 is hydrogen.

25. The compound of claim 23 , wherein R 2 is C 1 -C 4 alkyl.

26. The compound of claim 23 , wherein R 2 is C 2 -C 4 alkenyl.

27. The compound of claim 23 , wherein R 2 is C 2 -C 4 alkynyl.

28. The compound of claim 1 , wherein R 1 is hydrogen.

29. The compound of claim 1 , wherein R 1 is C 1 -C 4 alkyl or C 1 -C 4 haloalkyl.

30. The compound of claim 1 , wherein R 1 is —C(O)—C 1 -C 4 alkyl or —C(O)—C 1 -C 4 haloalkyl.

31. The compound of claim 1 , wherein R 1 is —C(O)O-C 1 -C 4 alkyl or —C(O)O—C 1 -C 4 haloalkyl.

32. The compound of claim 1 , wherein R 3 is hydrogen.

33. The compound of claim 1 , wherein R 3 is halogen.

34. The compound of claim 1 , wherein R 3 is C 1 -C 5 haloalkyl.

35. The compound of claim 1 , wherein R 3 is C 1 -C 5 alkoxy, C 1 -C 5 haloalkoxy, or cyano.

36. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

11-methyl-4-[(E)-2-(6-methylpyridin-3-yl)vinyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;

11-methyl-4-[2-(6-methylpyridin-3-yl)ethyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;

11-methyl-4-[(6-methylpyridin-3-yl)ethynyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;

11-methyl-2-[(E)-2-(6-methylpyridin-3-yl)vinyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;

(7R*,10S*)-4-(benzyloxy)-11-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;

(7S*,10R*)-4-(benzyloxy)-11-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;

(−)-(7R*,11S*)-4-(benzyloxy)-12-methyl-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;

(+)-(7S*,11R*)-4-(benzyloxy)-12-methyl-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;

(7R*,11S*)-4-(benzyloxy)-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;

(7S*,11R*)-4-(benzyloxy)-6,7,8,9,10,11-hexahydro-5H-7,11-epiminocycloocta[b]indole;

4-(4-chlorophenyl)-11-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;

2-fluoro-11-methyl-4-[(E)-2-(6-methylpyridin-3-yl)vinyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;

4-[(E)-2-(6-methylpyridin-3-yl)vinyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;

(+)-(7S*,10R*)-11-methyl-4-[(E)-2-(6-methylpyridin-3-yl)vinyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;

(−)-(7R*,10S*)-11-methyl-4-[(E)-2-(6-methylpyridin-3-yl)vinyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;

(+)-(7S*,10R*)-11-methyl-4-[(6-methylpyridin-3-yl)ethynyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;

(−)-(7R*,10S*)-11-methyl-4-[(6-methylpyridin-3-yl)ethynyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;

11-acetyl-4-[(E)-2-(6-methylpyridin-3-yl)vinyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;

methyl 4-[(E)-2-(6-methylpyridin-3-yl)vinyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole-11-carboxylate;

methyl 4-isoquinolin-7-yl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole-11-carboxylate;

11-acetyl-4-quinolin-3-yl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;

methyl 4-quinolin-6-yl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole-11-carboxylate;

11-acetyl-4-quinolin-6-yl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;

5-methyl-4-[(E)-2-(6-methylpyridin-3-yl)vinyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;

(7R,10S)-4-[(E)-2-(6-methylpyridin-3-yl)vinyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;

((7S,10R)-4-[(E)-2-(6-methylpyridin-3-yl)vinyl]-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;

4-(6-chloropyridin-3-yl)-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;

4-(6′-chloro-2,3′-bipyridin-5-yl)-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;

1-[4-(6-chloropyridin-3-yl)-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indol-11-yl]ethanone;

4-(pyridin-4-yl)-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;

4-(quinolin-3-yl)-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;

11-methyl-4-(6-methylpyridin-3-yl)-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;

11-methyl-4-(quinolin-3-yl)-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole;

4-(pyridin-3-yl)-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole; and

methyl 4-(quinolin-3-yl)-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole-11-carboxylate.

37. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) according to claim 1 .

38. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier.