Allosteric modulators of the A

1. A compound of formula (I)

wherein

R 1 is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl or substituted cycloalkyl;

R 2 , R 3 , and R 4 are, independently from each other, hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, halogen, hydroxyl, nitro, cyano, alkoxy or substituted alkoxy;

Q is selected from the group consisting of

 in which

R 5 is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, heteroaryl, substituted heteroaryl, heteroaralkyl, substituted heteroaralkyl, acyl or substituted acyl;

R 6 and R 7 are, independently from each other, hydrogen, C 1 -C 3 alkyl or C 1 -C 3 substituted alkyl; or

R 6 and R 7 , provided they are attached to the same carbon atom, combined are alkylene which together with the carbon atom to which they are attached form a 3- to 7-membered spirocyclic ring;

R 8 , R 9 , R 10 , R 11 , R 12 and R 13 are, independently from each other, hydrogen, C 1 -C 3 alkyl or C 1 -C 3 substituted alkyl;

X is C—H; or

X is C—NR 14 R 15 wherein R 14 and R 15 are, independently from each other, hydrogen, C 1 -C 3 alkyl, C 1 -C 3 substituted alkyl, aryl or substituted aryl; or

X is C—R 16 wherein R 16 and R 5 combined are a carbonyl oxygen; or

X is C—R 16 wherein R 16 and R 5 combined are a divalent radical of the formula

←Y—CHR 17 —(CH 2 ) n —CHR 18 —Y→

 which together with the carbon atom to which R 16 and R 5 are attached form a 5- to 7-membered spirocyclic ring, and in which

Y is oxygen or sulfur;

R 17 and R 18 are, independently from each other, hydrogen, C 1 -C 6 alkyl, C 1 -C 6 substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl or substituted aryl;

n is zero, or an integer of 1 or 2; or

X is C—R 16 wherein R 16 and R 5 combined are a divalent radical of the formula

 which together with the carbon atom to which R 16 and R 5 are attached form a 5-membered spirocyclic ring, and in which

Y is oxygen or sulfur;

R 19 and R 20 are, independently from each other, hydrogen, halogen, cyano, trifluoromethyl, C 1 -C 6 alkyl, C 1 -C 6 substituted alkyl or C 1 -C 6 alkoxy;

or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1 , wherein

R 1 is hydrogen, alkyl, substituted alkyl, aryl or substituted aryl;

or a pharmaceutically acceptable salt thereof.

3. A compound according to claim 2 , wherein Q is

in which

R 5 is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, heteroaryl, substituted heteroaryl, heteroaralkyl, substituted heteroaralkyl, acyl or substituted acyl;

R 6 and R 7 are, independently from each other, hydrogen, C 1 -C 3 alkyl or C 1 -C 3 substituted alkyl; or

R 6 and R 7 , provided they are attached to the same carbon atom, combined are alkylene which together with the carbon atom to which they are attached form a 3- to 7-membered spirocyclic ring;

X is C—H; or

X is C—NR 14 R 15 wherein R 14 and R 15 are, independently from each other, hydrogen, C 1 -C 3 alkyl, C 1 -C 3 substituted alkyl, aryl or substituted aryl; or

X is C—R 16 wherein R 16 and R 5 combined are a divalent radical of the formula

 which together with the carbon atom to which R 16 and R 5 are attached form a 5-membered spirocyclic ring, and in which

Y is oxygen or sulfur;

R 19 and R 20 are, independently from each other, hydrogen, halogen,

cyano, trifluoromethyl, C 1 -C 6 alkyl, C 1 -C 6 substituted alkyl or C 1 -C 6 alkoxy;

or a pharmaceutically acceptable salt thereof.

4. A compound according to claim 3 , wherein

X is C—R 16 wherein R 16 and R 5 combined are a divalent radical of the formula

 which together with the carbon atom to which R 16 and R 5 are attached form a 5-membered spirocyclic ring, and in which

Y is oxygen;

R 19 and R 20 are, independently from each other, hydrogen, halogen, cyano,

trifluoromethyl, C 1 -C 6 alkyl, C 1 -C 6 substituted alkyl or C 1 -C 6 alkoxy;

or a pharmaceutically acceptable salt thereof.

5. A compound according to claim 4 of formula (IB)

wherein

R 1 is hydrogen, alkyl, substituted alkyl, aryl or substituted aryl;

R 2 , R 3 , and R 4 are, independently from each other, hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, halogen, hydroxyl, nitro, cyano, alkoxy or substituted alkoxy;

R 6 , R 7 , R 8 and R 9 are, independently from each other, hydrogen, C 1 -C 3 alkyl or C 1 -C 3 substituted alkyl;

R 19 and R 20 are, independently from each other, hydrogen, halogen, cyano, trifluoromethyl, C 1 -C 6 alkyl, C 1 -C 6 substituted alkyl or C 1 -C 6 alkoxy;

or a pharmaceutically acceptable salt thereof.

6. A compound according claim 5 , wherein

R 1 is hydrogen or C 1 -C 3 alkyl;

or a pharmaceutically acceptable salt thereof.

7. A compound according to claim 5 , wherein

R 19 and R 20 are, independently from each other, hydrogen, halogen, cyano, trifluoromethyl or C 1 -C 4 alkyl;

or a pharmaceutically acceptable salt thereof.

8. A compound according to claim 5 , wherein

R 2 and R 4 are hydrogen;

or a pharmaceutically acceptable salt thereof.

9. A compound according to claim 8 , wherein

R 3 is halogen, cyano or trifluoromethyl;

or a pharmaceutically acceptable salt thereof.

10. A compound according to claim 5 , wherein

R 2 and R 3 are hydrogen;

or a pharmaceutically acceptable salt thereof.

11. A compound according to claim 10 , wherein

R 4 is halogen, cyano or trifluoromethyl;

or a pharmaceutically acceptable salt thereof.

12. A compound according to claim 5 , wherein

R 6 , R 7 , R 5 and R 9 are hydrogen;

or a pharmaceutically acceptable salt thereof.

13. A compound according to claim 12 , wherein

R 19 and R 20 are, independently from each other, hydrogen, halogen, cyano, trifluoromethyl or C 1 -C 4 alkyl;

or a pharmaceutically acceptable salt thereof.

14. A compound according to claim 13 , wherein

R 2 and R 4 are hydrogen;

or a pharmaceutically acceptable salt thereof.

15. A compound according to claim 14 , wherein

R 3 is halogen, cyano or trifluoromethyl;

or a pharmaceutically acceptable salt thereof.

16. A compound according claim 15 , wherein

R 1 is hydrogen or C 1 -C 3 alkyl;

or a pharmaceutically acceptable salt thereof.

17. A compound according to claim 13 , wherein

R 2 and R 3 are hydrogen;

or a pharmaceutically acceptable salt thereof.

18. A compound according to claim 17 , wherein

R 4 is halogen, cyano or trifluoromethyl;

or a pharmaceutically acceptable salt thereof.

19. A compound according claim 18 , wherein

R 1 is hydrogen or C 1 -C 3 alkyl;

or a pharmaceutically acceptable salt thereof.

20. A compound selected from the group consisting of:

{2-Amino-4-[(4-(4-chlorophenyl)piperidin-1-yl)methyl]thiophen-3-yl}(4-chlorophenyl)methanone;

{2-Amino-4-(spiro[benzo[d][1,3]-dioxole-2,4′piperidine]-1′-ylmethyl)thiophen-3-yl}(4-chlorophenyl)methanone;

{2-Amino-4-(5-tert-butylspiro[benzo[d][1,3]-dioxole-2,4′-piperidine]-1′-ylmethyl)thiophen-3-yl}(4-chlorophenyl)methanone;

{2-Amino-4-(4-fluorospiro[benzo[d][1,3]-dioxole-2,4′-piperidine]-1′-ylmethyl)thiophen-3-yl}(4-chlorophenyl)methanone;

{2-Amino-4-(4-methylspiro[benzo[d][1,3]-dioxole-2,4′piperidine]-1′-ylmethyl)thiophen-3-yl}(4-chlorophenyl)methanone;

{2-Amino-4-(5-methylspiro[benzo[d][1,3]-dioxole-2,4′-piperidine]-1′-ylmethyl)thiophen-3-yl}(4-chlorophenyl)methanone;

{2-Amino-4-[(4-(4-chlorophenylamino)piperidin-1-yl)methyl]thiophen-3-yl}(4-chlorophenyl)methanone;

{2-Amino-4-[(4-(4-chlorophenylmethylamino)piperidin-1-yl)methyl]thiophen-3-yl}(4-chlorophenyl)methanone; and

{2-Amino-5-phenyl-4-[(piperidin-1-yl)methyl]thiophen-3-yl}(4-chlorophenyl)methanone;

or a pharmaceutically acceptable salt thereof.

21. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 in combination with one or more pharmaceutically acceptable carriers.

22. A pharmaceutical composition according to claim 21 for the treatment of chronic pain.

23. A pharmaceutical composition according to claim 22 , wherein the chronic pain is neuropathic pain.

24. A method for the treatment of chronic pain in a mammal which method comprises administering to the mammal, in need thereof, a therapeutically effective amount of a compound of formula (I)

wherein

R 1 is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl or substituted cycloalkyl;

R 2 , R 3 , and R 4 are, independently from each other, hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, halogen, hydroxyl, nitro, cyano, alkoxy or substituted alkoxy;

Q is selected from the group consisting of

 in which

R 5 is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, heteroaryl, substituted heteroaryl, heteroaralkyl, substituted heteroaralkyl, acyl or substituted acyl;

R 6 and R 7 are, independently from each other, hydrogen, C 1 -C 3 alkyl or C 1 -C 3 substituted alkyl; or

R 6 and R 7 , provided they are attached to the same carbon atom, combined are alkylene which together with the carbon atom to which they are attached form a 3- to 7-membered spirocyclic ring;

R 8 , R 9 , R 10 , R 11 , R 12 and R 13 are, independently from each other, hydrogen, C 1 -C 3 alkyl or C 1 -C 3 substituted alkyl;

X is C—H; or

X is C—NR 14 R 15 wherein R 14 and R 15 are, independently from each other, hydrogen, C 1 -C 3 alkyl, C 1 -C 3 substituted alkyl, aryl or substituted aryl; or

X is C—R 16 wherein R 16 and R 5 combined are a carbonyl oxygen; or

X is C—R 16 wherein R 16 and R 5 combined are a divalent radical of the formula

←Y—CHR 17 —(CH 2 ) n —CHR 18 —Y→

 which together with the carbon atom to which R 16 and R 5 are attached form a 5- to 7-membered spirocyclic ring, and in which

Y is oxygen or sulfur;

R 17 and R 18 are, independently from each other, hydrogen, C 1 -C 6 alkyl, C 1 -C 6 substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl or substituted aryl;

n is zero, or an integer of 1 or 2; or

X is C—R 16 wherein R 16 and R 5 combined are a divalent radical of the formula

 which together with the carbon atom to which R 16 and R 5 are attached form a 5-membered spirocyclic ring, and in which

Y is oxygen or sulfur;

R 19 and R 20 are, independently from each other, hydrogen, halogen, cyano, trifluoromethyl, C 1 -C 6 alkyl, C 1 -C 6 substituted alkyl or C 1 -C 6 alkoxy;

or a pharmaceutically acceptable salt thereof.

25. A method according to claim 24 , wherein the chronic pain is neuropathic pain.