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

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

X is N;

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 of formula (IA)

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

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;

or a pharmaceutically acceptable salt thereof.

4. A compound according claim 3 , wherein

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

or a pharmaceutically acceptable salt thereof.

5. A compound according to claim 3 , wherein

R 5 is monocyclic aryl optionally substituted by one to three substituents selected from the group consisting of halogen, cyano or trifluoromethyl;

or a pharmaceutically acceptable salt thereof.

6. A compound according to claim 3 , wherein

R 2 and R 4 are hydrogen;

or a pharmaceutically acceptable salt thereof.

7. A compound according to claim 6 , wherein

R 3 is halogen, cyano or trifluoromethyl;

or a pharmaceutically acceptable salt thereof.

8. A compound according to claim 3 , wherein

R 2 and R 3 are hydrogen;

or a pharmaceutically acceptable salt thereof.

9. A compound according to claim 8 , wherein

R 4 is halogen, cyano or trifluoromethyl;

or a pharmaceutically acceptable salt thereof.

10. A compound according to claim 3 , wherein

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

or a pharmaceutically acceptable salt thereof.

11. A compound according to claim 10 , wherein

R 5 is monocyclic aryl optionally substituted by one to three substituents selected from the group consisting of halogen, cyano or trifluoromethyl;

or a pharmaceutically acceptable salt thereof.

12. A compound according to claim 11 , wherein

R 2 and R 4 are hydrogen;

or a pharmaceutically acceptable salt thereof.

13. A compound according to claim 12 , wherein

R 3 is halogen, cyano or trifluoromethyl;

or a pharmaceutically acceptable salt thereof.

14. A compound according claim 13 , wherein

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

or a pharmaceutically acceptable salt thereof.

15. A compound according to claim 11 , wherein

R 2 and R 3 are hydrogen;

or a pharmaceutically acceptable salt thereof.

16. A compound according to claim 15 , wherein

R 4 is halogen, cyano or trifluoromethyl;

or a pharmaceutically acceptable salt thereof.

17. A compound according claim 16 , wherein

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

or a pharmaceutically acceptable salt thereof.

18. A compound selected from the group consisting of:

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

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

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

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

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

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

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

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

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

4-{4-[(5-Amino-4-(4-chlorobenzoyl)thiophen-3-yl)methyl]piperazin-1-yl}benzonitrile;

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

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

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

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

1-{4-[(5-Amino-4-(4-chlorobenzoyl)thiophen-3-yl)methyl]piperazin-1-yl}-2-(4-chlorophenyl)ethanone;

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

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

{2-Amino-4-[(4-(benzo[d][1,3]dioxol-5-yl)piperazin-1-yl)methyl]thiophen-3-yl}(4-chlorophenyl)methanone;

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

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

{2-Amino-4-[(4-(3,5-dichlorophenyl)piperazin-1-yl)methyl]thiophen-3-yl}(4-chlorophenyl)methanone;

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

2-{4-[(5-Amino-4-(4-chlorobenzoyl)thiophen-3-yl)methyl]piperazin-1-yl}-1-(4-chlorophenyl)ethanone;

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

{2-Amino-4-[(4-(2,6-difluorophenyl)piperazin-1-yl)methyl]thiophen-3-yl}(4-chlorophenyl)methanone;

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

{2-Amino-4-[(4-(2,5-difluorophenyl)piperazin-1-yl)methyl]thiophen-3-yl}(4-chlorophenyl)methanone;

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

{2-Amino-4-[(4-(4-chloro-3-(trifluoromethyl)phenyl)piperazin-1-yl)methyl]thiophen-3-yl}(4-chlorophenyl)methanone;

{2-Amino-4-[(4-(2,4,6-trifluorophenyl)piperazin-1-yl)methyl]thiophen-3-yl}(4-chlorophenyl)methanone;

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

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

{2-Amino-4-[(4-(3,5-diflourophenyl)piperazin-1-yl)methyl]thiophen-3-yl}(4-chlorophenyl)methanone;

{2-Amino-4-[(4-(2,6-dichlorophenyl)piperazin-1-yl)methyl]thiophen-3-yl}(4-chlorophenyl)methanone;

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

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

{2-Amino-4-[(4-(2,5-dichlorophenyl)piperazin-1-yl)methyl]thiophen-3-yl}(4-chlorophenyl)methanone;

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

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

{2-Amino-4-[(4-(4-(trifluoromethyl)phenyl)piperazin-1-yl)methyl]thiophen-3-yl}[3-(trifluoromethyl)phenyl]methanone;

{2-Amino-4-[(4-(3-fluorophenyl)piperazin-1-yl)methyl]thiophen-3-yl}[3-(trifluoromethyl)phenyl]methanone;

{2-Amino-4-[(4-(2,6-difluorophenyl)piperazin-1-yl)methyl]thiophen-3-yl}[3-(trifluoromethyl)phenyl]methanone;

{2-Amino-4-[(4-(4-fluorophenyl)piperazin-1-yl)methyl]-5-methylthiophen-3-yl}(4-chlorophenyl)methanone;

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

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

{2-Amino-4-[(4-(4-chlorophenyl)piperazin-1-yl)methyl]-5-methylthiophen-3-yl}(4-chlorophenyl)methanone;

{2-Amino-4-[(4-(4-bromophenyl)piperazin-1-yl)methyl]-5-methylthiophen-3-yl}(4-chlorophenyl)methanone;

{2-Amino-4-[(4-(4-iodophenyl)piperazin-1-yl)methyl]-5-methylthiophen-3-yl}(4-chlorophenyl)methanone;

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

4-{4-[(5-Amino-4-(4-chlorobenzoyl)-2-methylthiophen-3-yl)methyl]piperazin-1-yl}benzonitrile;

{2-Amino-4-[(4-benzylpiperazin-1-yl)methyl)-5-methylthiophen-3-yl](4-chlorophenyl)methanone;

{2-Amino-4-[(4-(4-methoxyphenyl)piperazin-1-yl)methyl]-5-methylthiophen-3-yl}(4-chlorophenyl)methanone;

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

{2-Amino-4-[(4-(3,4-dichlorophenyl)piperazin-1-yl)methyl]-5-methylthiophen-3-yl}(4-chlorophenyl)methanone;

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

{2-Amino-4-[(4-(3-chlorophenyl)piperazin-1-yl)methyl]-5-methylthiophen-3-yl}(4-chlorophenyl)methanone;

{2-Amino-4-[(4-(4-chloro-3-(trifluoromethyl)phenyl)piperazin-1-yl)methyl]-5-methylthiophen-3-yl}(4-chlorophenyl)methanone;

{2-Amino-4-[4-(4-fluorophenyl)piperazin-1-yl)methyl]-5-ethylthiophen-3-yl}(4-chlorophenyl)methanone;

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

{2-Amino-4-[(4-(4-chlorophenyl)piperazin-1-yl)methyl]-5-ethylthiophen-3-yl}(4-chlorophenyl)methanone; and

{2-Amino-4-[(4-(3-fluorophenyl)piperazin-1-yl)methyl]-5-methylthiophen-3-yl}(4-chlorophenyl)methanone;

or a pharmaceutically acceptable salt thereof.

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

20. A pharmaceutical composition according to claim 19 for the treatment of pain, cardiac disease or disorder, neurological disease or injury, sleep disorder, epilepsy and depression.

21. A pharmaceutical composition according to claim 20 , wherein the pain is neuropathic pain.