Substituted benzimidazole-type piperidine compounds and uses thereof

1. A compound of Formula (I ‡ A):

or a pharmaceutically acceptable salt or solvate thereof wherein:

the Q a ring is fused benzo or fused (5- or 6-membered)heteroaryl;

each R 2 is independently selected from:

(a) -halo, —CN, —NO 2 , —OT 3 , —C(═O)T 3 , —C(═O)OT 3 , —C(═O)N(T 1 )(T 2 ), —S(═O) 2 OT 3 , —S(═O)T 3 , —S(═O) 2 T 3 , —O —S(═O) 2 T 3 , —S(═O) 2 N(T 1 )(T 2 ), —N(T 1 )(T 2 ), —N(T 3 )C(═O)T 3 , —N(T 3 )C(═O)N(T 1 )(T 2 ), —N(T 3 )S(═O)T 3 , —N(T 3 )S(═O) 2 T 3 , —N(T 3 )C(═O)OT 3 , and —N(T 3 )S(═O) 2 N(T 1 )(T 2 ); and

(b) —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 1 -C 6 )alkoxy, —(C 3 -C 7 )cycloalkyl, —(C 6 -C 10 )bicycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 7 -C 10 )bicycloalkenyl, and -(5-or 6-membered)heterocycle, each of which is unsubstituted or substituted with 1, 2, or 3 independently selected R 8 groups; and

(c) -phenyl, -naphthalenyl, and -(5- or 6- membered)heteroaryl, each of which is unsubstituted or substituted with 1, 2, or 3 independently selected R 7 groups;

each dashed line denotes the presence or absence of a bond, provided that:

(a) one dashed line must denote the presence of a bond;

(b) when one dashed line denotes the presence of a bond then the other dashed line denotes the absence of a bond;

(c) when the dashed line within the 5-membered, nitrogen-containing ring that is fused to the Q a ring is present, then R 3 is absent; and

(d) when the dashed line within the 5-membered, nitrogen-containing ring that is fused to the Q a ring is absent, then R 3 is present;

R 3 , when present, is:

(a) —H; or

(b) —(C 1 -C 4 )alkyl which is unsubstituted or substituted with 1, 2, or 3 groups independently selected from —OH, —(C 1 -C 4 )alkoxy, —N(R 6 ) 2 , —C(═O) OR 9 , and —C(═O)N(R 6 ) 2 ; or

(c) —(C 3 -C 7 )cycloalkyl which is unsubstituted or substituted with 1, 2, or 3 groups independently selected from —OH, —(C 1 -C 4 )alkoxy, —N(R 6 ) 2 , —C(═O)OR 9 , and —C(═O)N(R 6 ) 2 ;

U 1 is C, CH, or N;

U 2 is a bond, N, N(R 4 ), O or S, provided that when U 1 is C or CH, U 2 is N or N(R 4 );

t is an integer selected from 0, 1, 2, and 3;

when t is 0, the Q x ring is a -(4-, 5-, 6-, or 7-membered)heterocycle containing 1, 2, 3, or 4 ring heteroatoms selected from N, N(R 4 ), O and S wherein said heterocycle is unsubstituted or substituted with)(R 10 ) s groups provided that at least one ring heteroatom is N or N(R 4 ) and provided that when the dashed line connecting the Q x ring to the 5-membered, nitrogen-containing ring that is fused to the Q a ring is present, U 1 is C or CH, and

when t is 1, 2, or 3 the Q x ring is a (5- or 6-membered)heterocycle selected from:

each R 4 , when present, is independently selected from:

(a) —H; and

(b) —X, —(C 1 -C 6 )alkyl-X -(5- or 6-membered)heterocycle-X, or -(5- or 6-membered)heterocycle—(C 1 -C 6 )alkyl-X; and

(c) —(CH 2 ) d —C(═Y)CN, —(CH 2 ) d —C(═Y)X, —(CH 2 ) d —C(═Y)T 3 , —(CH 2 ) d —C(═Y)YX, —(CH 2 ) d —C(═Y)YT 3 , —(CH 2 ) d —C(═Y)N(T 1 )(T 2 ), —(CH 2 ) d —C(═Y)N(R 9 )CN, —(CH 2 ) d —C(═Y)N(R 9 )X, —(CH 2 ) d —C(═Y)N(R 9 )YH, —(CH 2 ) d —C(═Y)N(R 9 )YX, —(CH 2 ) d —C(═Y)N(R 9 )YCH 2 X, —(CH 2 ) d —C(═Y)N(R 9 )YCH 2 CH 2 X, —(CH 2 ) d —C(═Y)N(R 9 )S(═O) 2 T 3 , —(CH 2 ) d —N(R 9 )S(═O), 2 T 3 , or —(CH 2 ) d —S(═O) 2 T 4 ; and

(d) —[CH 2 —O] b —R 16 , —[CH(CH 3 )—O] b —R 16 , —[CH 2 —CH 2 —O] b ,—R 16 , —[CH(CH 3 )—CH 2—O] b —R 16 , —[CH 2 —CH(CH 3 )—O] b —R 16 , —[CH 2 —CH 2 CH 2 —O] b —R 16 , —[CH(CH 3 )—CH 2 —CH 2 —O] b —R 16 , —[CH 2 —CH(CH 3 )—CH 2 —O] b —R 16 , or —[CH 2 —CH 2 —CH(CH 3 )—O] b —R 16 ;

X is selected from:

(a) —H, —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C 1 -C 6 )alkoxy, —(C 3 -C 7 )cycloalkyl, —(C 5 -C 10 )cycloalkenyl, and -(5- or 6-membered)heterocycle, each of which is unsubstituted or substituted with 1, 2, or 3 independently selected R 8 groups; and

(b) -phenyl and -(5- or 6-membered)heteroaryl, each of which is unsubstituted or substituted with 1, 2, or 3 independently selected R 7 groups;

each Y is independently O or S;

each R 16 is independently H or CH 3 ;

s is an integer selected from 0, 1, 2, 3, and 4;

when s is 1, 2, 3, or 4, each R 10 is independently —F, —Cl, —CH 3 , —CH 2 CH 3 , —OCH 3 , —OCH 2 CH 3 , —(CH 2 ) d —C(═Y)YT 3 , or —(CH 2 ) d —C(═Y)N(T 1 )(T 2 ), and when s is 2, 3, or 4, each R 10 is independently —F, —Cl, —CH 3 , —CH 2 CH 3 , —OCH 3 , —OCH 2 CH 3 , —(CH 2 ) d —C(═Y)YT 3 , or —(CH 2 ) d —C(═Y)N(T 1 )( T 2 ) or two R 10 groups attached to the same carbon atom and are gem-dimethyl, gem-difluoro, ═O, or ═S;

A and B together form a (C 2 -C 6 )bridge, which is unsubstituted or substituted with 1, 2, 3, 4, 5, 6, 7, or 8 substituents independently selected from —OH, —(C 1 -C 4 )alkyl, -halo, and —C(halo) 3 , and which bridge optionally contains —HC═CH— or —O— within the (C 2 -C 6 )bridge; wherein the 5-membered, nitrogen-containing ring that is fused to the Q a ring can be in the endo- or exo- configuration with respect to the A-B bridge;

Z is —[(C 1 -C 10 )alkyl optionally substituted by R 13 ] h —, wherein h is 0 or 1; or —[(C 2 -C 10 )alkenyl optionally substituted by R 13 ]—, or —[(C 1 -C 10 )alkyl-NR 6 C(═Y)]—;

R 1 is selected from:

(a) —H, -halo, —CN, —OH, —CH 2 OH, —CH 2 CH 2 OH, —NO 2 , —N(R 6 ) 2 , —S(═O)NH 2 , —S(═O) 2 NH 2 , —C(═O)OV 1 , and —C(═O)CN; and

(b) —(C 1 -C 10 )alkyl, —(C 2 -C 10 )alkenyl, —(C 2 -C 10 )alkynyl, —O(C 1 -C 6 )alkyl, —(C 3 -C 7 )cycloalkoxy, —(C 6 -C 14 )bicycloalkyl, —(C 8 -C 20 )tricycloalkyl, —(C 5 -C 10 )cycloalkenyl, —(C 7 -C 14 )bicycloalkenyl, —(C 8 -C 20 )tricycloalkenyl, and -(3- to 7-membered)heterocycle, each of which is unsubstituted or substituted with 1, 2, 3, or 4 independently selected R 8 groups; and

(c)

(d) -phenyl, -naphthalenyl, —(C 14 )aryl, and -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with 1, 2, 3, or 4 independently selected re groups;

each R 5 is independently —(C 1 -C 4 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, -(5- or 6-membered)heteroaryl, —(C 1 -C 6 )alkyl-C(═O)OR 9 —OR 9 , —SR 9 , —C(halo) 3 , —CH(halo) 2 , —CH 2 (halo), —CN, ═O, ═S, -halo, —N 3 , —NO 2 , —CH═N(R 9 ), —N(R 9 )(C 1 -C 6 )alkyl-C(═O)OR 9 , —N(R 9 ) 2 , —N(R 9 )OH, —N(R 9 )S(═O)R 12 , —N(R 9 )S(═O) 2 R 12 , —N(R 9 )C(═O)R 12 , —N(R 9 )C(═O)OR 12 , —C(═O)R 9 , —C(═O)OR 9 , —OC(═O)R 9 , —OC(═O)OR 9 , —S(═O)R 9 , or —S(═O) 2 R 9 ;

each R 6 is independently —H, —(C 1 -C 6 )alkyl, or —(C 3 -C 7 )cycloalkyl, or two R 6 groups attached to the same nitrogen atom can together form a -(5- to 8-membered)heterocyclic ring, wherein the number of atoms in the ring includes the nitrogen atom, and in which one of the -(5- to 8-membered)heterocyclic ring carbon atoms is optionally replaced by O, S, or N(T 3 );

each R 7 is independently —(C 1 -C 4 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —OR 9 , —SR 9 , —C(halo) 3 , —CH(halo) 2 , —CH 2 ,(halo), —CN, -halo, —N 3 , —NO 2 , —CH═N(R 9 ), —N(R 9 ) 2 , —N(R 9 )OH, —N(R 9 )S(═O)R 12 , —N(R 9 )S(═O) 2 R 12 , —N(R 9 )C(═O)R 12 , —N(R 9 )C(═O)N(T 1 )(T 2 ), —N(R 9 )C(═O)OR 12 , —C(═O)R 9 , —C(═O)N(T 1 )(T 2 ), —C(═O)OR 9 , —OC(═O)R 9 , —OC(═O)N(T 1 )(T 2 ), —OC(═O)OR 9 , —S(═O)R 9 , or —S(═O) 2 R 9 ;

each R 8 is independently —(C 1 -C 4 )alkyl, —(C 2 -C 6 )alkenyl, —(C2-C 6 )alkynyl, -(5- or 6-membered)heteroaryl, —(C 1 -C 6 )alkyl-C(═O)OR 9 , —N(R 9 )(C 1 -C 6 )alkyl-C(═O)OR 9 , —OR 9 , —SR 9 , —C(halo) 3 , —CH(halo) 2 , —CH 2 (halo), —CN, ═O, ═S, ═N(R 9 ), -halo, —N 3 , —NO 2 , —CH═N(R 9 ), —N(R 9 ) 2 , —N(R 9 )OR 9 , —N(R 9 )S(═O)R 12 , —N(R 9 )S(═O) 2 R 12 , —N(R 9 )C(═O)R 12 , —N(R 9 )C(═O)N(T 1 )(T 2 ), —N(R 9 )C(═O)OR 12 , —C(═O)R 9 , —C(═O)N(T 1 )(T 2 ), —C(═O)OR 9 , —OC(═O)R 9 , —OC(═O)N(T 1 )(T 2 ), —OC(═O)OR 9 , —S(═O)R 9 , or —S(═O) 2 (halo);

each R 9 is independently —H, —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 2 -C 6 )alkynyl, —(C3-C 8 )cycloalkyl, —(C 5 -C 8 )cycloalkenyl, -phenyl, -benzyl, -(3- to 7-membered)heterocycle, —C(halo) 3 , —CH(halo) 2 , or —CH 2 (halo);

each R 12 is independently —H or —(C 1 -C 4 )alkyl;

R 13 is selected from:

(a) -halo, —CN, —OH, —CH 2 OH, —CH 2 CH 2 OH, —NO 2 , —N(R 6 ) 2 , —S(═O)NH 2 , —S(═O) 2 NH 2 , —C(═O)OV 1 , and —C(═O)CN; and

(b) —(C 1 -C 10 )alkyl, —(C 2 -C 10 )alkenyl, —(C 2 -C 10 )alkynyl, —O(C 1 -C 6 )alkyl, -(C 3 -C 7 )cycloalkoxy, —(C 5 -C 10 )cycloalkenyl, and -(3- to 7-membered)heterocycle, each of which is unsubstituted or substituted with 1, 2, 3, or 4 independently selected R 8 groups; and

(c)

(d) -phenyl and -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with 1, 2, or 3 independently selected R 7 groups;

each T 1 and T 2 is independently —H or —(C 1 -C 10 )alkyl which is unsubstituted or substituted with 1, 2, or 3 independently selected R 5 groups and, optionally, in which any —(C 1 —C 10 )alkyl carbon atom except the carbon atom bonded directly to the atom to which T 1 or T 2 is attached is independently replaced by O, S, or N(R 6 ), or T 1 and T 2 can together form a -(5- to 8-membered)heterocyclic ring wherein the number of atoms in the ring includes the nitrogen atom to which T 1 and T 2 are bonded, said -(5- to 8-membered)heterocyclic ring is unsubstituted or substituted with 1, 2, or 3 independently selected R 5 groups and, optionally, any 1 or 2 carbon atoms in said -(5- to 8-membered)heterocyclic ring is independently replaced by O, S, or N(R 6 );

each T 3 is independently —H or —(C 1 -C 10 )alkyl which is unsubstituted or substituted with 1, 2, or 3 independently selected R 5 groups and, optionally, in which any —(C 1 -C 10 )alkyl carbon atom except the carbon atom bonded directly to the atom to which T 3 is attached is independently replaced by O, S, or N(R 12 );

each T 4 is independently a -(5- or 6-membered)heteroaryl which is unsubstituted or substituted with 1 or 2 independently selected R 12 groups;

each V 1 is independently —H, —(C 1 -C 6 )alkyl, -(C 3 -C 7 )cycloalkyl, -phenyl, or -benzyl;

a is an integer selected from 0, 1, and 2;

each b is, independently, an integer selected from 1, 2, 3, 4, 5, and 6;

each d is, independently, an integer selected from 0, 1, 2, and 3;

m is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11;

n is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9;

e and f are each an integer independently selected from 0, 1, 2, 3, 4, and 5 provided that 2≦(e+f)≦5;

each p is an integer independently selected from 0, 1, 2, 3, and 4; and

each halo is independently —F, —Cl, —Br, or —I.

2. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein Q a is benzo, pyridino, pyrimidino, pyrazino, or pyridazino wherein the 2- and 3-positions of the pyridino are fused to the 5-membered, nitrogen-containing ring.

3. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein Q a is benzo.

4. The compound of claim 3 or a pharmaceutically acceptable salt or solvate thereof, wherein a is 0.

5. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein:

Q a is benzo;

a is 0;

A-B together form a (C 2 -C 6 )bridge, which is unsubstituted or substituted with 1, 2, 3, 4, 5, 6, 7 or 8 substituents independently selected from —OH, —(C 1 -C 4 )alkyl, -halo, and —C(halo) 3 , and which bridge optionally contains —HC═CH— or —O— within the (C 2 -C 6 )bridge; wherein the A-B bridge can be in the endo- or exo- configuration with respect to the 5-membered, nitrogen-containing ring that is fused to the Q a ring;

Z is —[(C 1 -C 10 )alkyl] h —, wherein h is 0 or 1; and

R 1 is selected from:

(a) —CN, —OH, —CH 2 OH, —CH 2 CH 2 OH, —NO 2 , —N(R 6 ) 2 , —S(═O)NH 2 , —S(═O) 2 NH 2 , —C(═O)OV 1 , and —C(═O)CN; and

(b) —(C 1 -C 10 )alkyl, —O(C 1 -C 6 )alkyl, —(C 3 -C 7 )cycloalkoxy, —(C 3 -C 14 )cycloalkyl, —(C 6 -C 14 )bicycloalkyl, —(C 8 -C 20 )tricycloalkyl, —(C 5 -C 14 )cycloalkenyl, —(C 7 -C 14 )bicycloalkenyl, —(C 8 -C 20 )tricycloalkenyl, and -(3- to 7-membered)heterocycle, each of which is unsubstituted or substituted with 1, 2, 3, or 4 independently selected R 8 groups; and

(c)

 and

(d) -phenyl and -(5- to 10-membered)heteroaryl, each of which is unsubstituted or substituted with 1, 2, or 3 independently selected R 7 groups.

6. The compound of claim 5 or a pharmaceutically acceptable salt or solvate thereof, wherein each b is, independently, an integer selected from 2 and 3.

7. The compound of claim 6 or a pharmaceutically acceptable salt or solvate thereof, wherein each b is 3.

8. The compound of claim 5 or a pharmaceutically acceptable salt or solvate thereof, wherein t is 1 and the Q x ring is selected from:

9. The compound of claim 8 or a pharmaceutically acceptable salt or solvate thereof, wherein the Q x ring is selected from:

10. The compound of claim 9 or a pharmaceutically acceptable salt or solvate thereof, wherein s is 0.

11. The compound of claim 5 or a pharmaceutically acceptable salt or solvate thereof, wherein t is 1, 2, or 3 and the Q x ring is selected from:

12. The compound of claim 5 or a pharmaceutically acceptable salt or solvate thereof, wherein t is 0 and the Q x ring is selected from:

13. The compound of claim 12 or a pharmaceutically acceptable salt or solvate thereof, wherein s is 0.

14. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein the dashed line within the 5-membered, nitrogen-containing ring that is fused to the Q a ring is present to provide one bond of a double bond.

15. A compound which is:

or a pharmaceutically acceptable salt or solvate thereof.

16. The compound of claim 15 which is:

or a pharmaceutically acceptable salt or solvate thereof.

17. The compound of claim 5 or a pharmaceutically acceptable salt or solvate thereof, wherein h is 1.

18. The compound of claim 17 or a pharmaceutically acceptable salt or solvate thereof, wherein Z is —(C 1 -C 3 )alkyl- optionally substituted by R 13 .

19. The compound of claim 18 or a pharmaceutically acceptable salt or solvate thereof, wherein R 13 is absent.

20. The compound of claim 19 or a pharmaceutically acceptable salt or solvate thereof, wherein R 13 is absent and Z is —CH 2 —CH 2 —.

21. The compound of claim 20 or a pharmaceutically acceptable salt or solvate thereof, wherein —Z—R 1 is:

wherein each R z is independently —H, —CH 3 , or —CH 2 CH 3 .

22. The compound of claim 5 or a pharmaceutically acceptable salt or solvate thereof, wherein h is 0.

23. The compound of claim 22 or a pharmaceutically acceptable salt or solvate thereof, wherein A and B together form a bridge such that the bridged-piperidine is:

wherein each R d is independently —H, —(C 1 -C 4 )alkyl, -halo, or —C(halo) 3 .

24. The compound of claim 23 or a pharmaceutically acceptable salt or solvate thereof, wherein A and B together form a bridge such that the bridged-piperidine is:

25. The compound of claim 24 or a pharmaceutically acceptable salt or solvate thereof, wherein the A-B bridge of the bridged-piperidine is in the endo- configuration with respect to the 5-membered, nitrogen-containing ring that is fused to the Q a ring.

26. The compound of claim 24 or a pharmaceutically acceptable salt or solvate thereof, wherein:

(a) R 1 is —(C 3 -C 14 )cycloalkyl, —(C 5 -C 14 )cycloalkenyl, —(C 6 -C 14 )bicycloalkyl, —(C 7 -C 14 )bicycloalkenyl, or —(C 8 -C 20 )tricycloalkyl, each of which is unsubstituted or substituted with 1, 2, 3, or 4 independently selected R 8 groups; and

(b) each R 8 is independently —(C 1 -C 4 )alkyl, —(C 1 -C 6 )alkyl-C(═O)OR 9 , —N(R 9 )(C 1 -C 6 )alkyl-C(═O)OR 9 , —OR 9 , —C(halo) 3 , —CH(halo) 2 , —CH 2 (halo), -halo, —N(R 9 ) 2 , —C(═O)N(T 1 )(T 2 ), or —C(═O)OR 9 .

27. The compound of claim 26 or a pharmaceutically acceptable salt or solvate thereof, wherein —Z—R 1 is:

28. The compound of claim 26 or a pharmaceutically acceptable salt or solvate thereof, wherein —Z—R 1 is:

wherein each R z is independently —H, —CH 3 , or —CH 2 CH 3 .

29. The compound of claim 28 or a pharmaceutically acceptable salt or solvate thereof, wherein —Z—R 1 is:

wherein R z is —H, —CH 3 , or —CH 2 CH 3 .

30. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein a is 1 and R 2 is -halo.

31. The compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein the R 1 group is in the exo-configuration with respect to the A-B bridge of the bridged piperidine.

32. The compound of claim 15 , wherein the pharmaceutically acceptable salt is a hydrochloride-salt, a sodium-salt, a potassium-salt, or a para-toluenesulfonic acid-salt.

33. The compound of claim 1 , wherein the pharmaceutically acceptable salt is a hydrochloride-salt, a sodium-salt, a potassium-salt, or a para-toluenesulfonic acid-salt.

34. The compound of claim 16 , wherein the pharmaceutically acceptable salt is a hydrochloride-salt, a sodium-salt, a potassium-salt, or a para-toluenesulfonic acid-salt.

35. A composition comprising an effective amount of the compound or a pharmaceutically acceptable salt or solvate of the compound of claim 15 and a pharmaceutically acceptable carrier or excipient.

36. A composition comprising an effective amount of the compound or a pharmaceutically acceptable salt or solvate of the compound of claim 1 and a pharmaceutically acceptable carrier or excipient.

37. A composition comprising an effective amount of the compound or a pharmaceutically acceptable salt or solvate of the compound of claim 16 and a pharmaceutically acceptable carrier or excipient.

38. A method for modulating ORL-1 receptor function in a cell, comprising contacting a cell capable of expressing the ORL-1 receptor with an effective amount of the composition or the compound or a pharmaceutically acceptable salt or solvate of the compound of claim 1 .

39. The method of claim 38 wherein the composition or the compound or the pharmaceutically acceptable salt or solvate of the compound acts as an agonist or as a partial agonist at the ORL-1 receptor.

40. The compound of claim 10 which is:

or a pharmaceutically acceptable salt thereof.

41. The compound of claim 40 , wherein the pharmaceutically acceptable salt is a hydrochloride-salt, a sodium-salt, a potassium-salt, or a para-toluenesulfonic acid-salt.

42. A method for modulating ORL-1 receptor function in a cell, comprising contacting a cell capable of expressing the ORL-1 receptor with an effective amount of the composition or the compound or a pharmaceutically acceptable salt or solvate of the compound of claim 15 .

43. The method of claim 42 wherein the composition or the compound or the pharmaceutically acceptable salt or solvate of the compound acts as an agonist or as a partial agonist at the ORI,-1 receptor.

44. A method for modulating ORL-1 receptor function in a cell, comprising contacting a cell capable of expressing the ORL-1 receptor with an effective amount of the composition or the compound or a pharmaceutically acceptable salt or solvate of the compound of claim 16 .

45. The method of claim 44 wherein the composition or the compound or the pharmaceutically acceptable salt or solvate of the compound acts as an agonist or as a partial agonist at the ORL-1 receptor.

46. A method for modulating ORL-1 receptor function in a cell, comprising contacting a cell capable of expressing the ORL-1 receptor with an effective amount of the composition or the compound or a pharmaceutically acceptable salt or solvate of the compound of claim 40 .

47. The method of claim 46 wherein the composition or the compound or the pharmaceutically acceptable salt or solvate of the compound acts as an agonist or as a partial agonist at the ORL-1 receptor.