Heterocyclic amide derivatives as P2X

1. A compound of the formula (I),

wherein

n represents 1, 2 or 3;

X represents —O— or —CH 2 —;

R 3 represents hydrogen, (C 1 -C 2 )alkyl or hydroxy-(C 1 -C 2 )alkyl;

R 2 represents hydrogen and R 3 represents heterocyclyl; or R 2 and R 3 form, together with the carbon atom to which they are attached, a 5- to 7-membered saturated carbocyclic ring which is unsubstituted or mono- or di-substituted with fluoro; and

R 4 represents hydrogen or heteroaryl which is unsubstituted or mono- or di-substituted with (C 1 -C 4 )alkyl, (C 1 -C 3 )fluoroalkyl or halogen;

or a salt of such a compound.

2. The compound of formula (I) according to claim 1 , wherein

n represents 1 or 2;

X represents —O— or —CH 2 —;

R 1 represents hydrogen;

R 2 represents hydrogen and R 3 represents heterocyclyl; or R 2 and R 3 form, together with the carbon atom to which they are attached, a 6- or 7-membered saturated carbocyclic ring which is unsubstituted or mono- or di-substituted with fluoro; and

R 4 represents heteroaryl which is unsubstituted or mono- or di-substituted with (C 1 -C 4 )alkyl, (C 1 -C 3 )fluoroalkyl or halogen;

or a salt of such a compound.

3. The compound of formula (I) according to claim 1 , wherein

n represents 1 or 2;

X represents —O— or —CH 2 —;

IV represents hydrogen;

R 2 and R 3 form, together with the carbon atom to which they are attached, a 6-membered saturated carbocyclic ring which is unsubstituted or di-substituted with fluoro; and

R 4 represents a 6-membered heteroaryl group, which group is mono-substituted with chloro;

or a salt of such a compound.

4. The compound of formula (I) according to claim 1 , wherein

X represents —O—;

or a salt of such a compound.

5. The compound of formula (I) according to claim 1 , wherein

X represents —CH 2 —;

or a salt of such a compound.

6. The compound of formula (I) according to claim 1 , wherein

R 2 represents hydrogen and R 3 represents heterocyclyl;

or a salt of such a compound.

7. The compound of formula (I) according to claim 1 , wherein

R 2 and R 3 form, together with the carbon atom to which they are attached, a 6-membered saturated carbocyclic ring which is unsubstituted or di-substituted with fluoro;

or a salt of such a compound.

8. The compound of formula (I) according to claim 1 , wherein

R 4 represents a 6-membered heteroaryl group, which group is unsubstituted or mono-substituted with methyl, trifluoromethyl or chloro;

or a salt of such a compound.

9. The compound of formula (I) according to claim 1 , selected from the group consisting of:

N-(1-cycloheptyl-2-hydroxyethyl)-5,6-dihydrofuro[2,3-d]thiazole-6-carboxamide;

N-((1-(6-chloropyridin-3-yl)cyclohexyl)methyl)-5,6-dihydrofuro[2,3-d]thiazole-6-carboxamide;

N-(2-(4,4-difluoropiperidin-1-yl)-2-(2-methylpyrimidin-5-yl)ethyl)-5,6-dihydrofuro[2,3-d]thiazole-6-carboxamide;

N-(2-morpholino-2-(6-(trifluoromethyl)pyridin-3-yl)ethyl)-5,6-dihydrofuro[2,3-d]thiazole-6-carboxamide;

N—((S)-1-cyclohexyl-2-hydroxyethyl)-5,6-dihydro-4H-cyclopenta[d]thiazole-6-carboxamide;

N-(2-(2-methylpyrimidin-5-yl)-2-morpholinoethyl)-5,6-dihydro-4H-cyclopenta[d]thiazole-6-carboxamide;

N-(2-(4,4-difluoropiperidin-1-yl)-2-(2-methylpyrimidin-5-yl)ethyl)-5,6-dihydro-4H-cyclopenta[d]thiazole-6-carboxamide;

N—((S)-1-cyclohexyl-2-hydroxyethyl)-6,7-dihydro-5H-pyrano[2,3-d]thiazole-7-carboxamide;

N-(2-(2-methylpyrimidin-5-yl)-2-morpholinoethyl)-6,7-dihydro-5H-pyrano[2,3-d]thiazole-7-carboxamide;

N-(2-(6-chloropyridin-3-yl)-2-(4,4-difluoropiperidin-1-yl)ethyl)-6,7-dihydro-5H-pyrano[2,3-d]thiazole-7-carboxamide;

N—((R)-1-cyclohexylethyl)-4,5,6,7-tetrahydrobenzo[d]thiazole-7-carboxamide;

N—((S)-1-cyclohexyl-2-hydroxyethyl)-4,5,6,7-tetrahydrobenzo[d]thiazole-7-carboxamide;

N-((1-(6-chloropyridin-3-yl)cyclohexyl)methyl)-4,5,6,7-tetrahydrobenzo[d]thiazole-7-carboxamide;

N-((1-(6-chloropyridin-3-yl)-4,4-difluorocyclohexyl)methyl)-4,5,6,7-tetrahydrobenzo[d]thiazole-7-carboxamide;

N-(2-morpholino-2-(2-(trifluoromethyl)pyrimidin-5-yl)ethyl)-4,5,6,7-tetrahydrobenzo[d]thiazole-7-carboxamide;

N—((S)-1-cyclohexyl-2-hydroxyethyl)-(S)-5,6,7,8-tetrahydro-4H-cyclohepta[d]thiazole-8-carboxamide; and

N—((S)-1-cyclohexyl-2-hydroxyethyl)-(R)-5,6,7,8-tetrahydro-4H-cyclohepta[d]thiazole-8-carboxamide;

or a salt of such a compound.

10. A pharmaceutical composition containing, as active principle, the compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert excipient.

11. A pharmaceutical composition containing, as active principle, a compound of formula (I) according to claim 9 , or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert excipient.

12. A method for the treatment of a disease selected from spinal cord injury, stroke, Alzheimer's disease, epilepsy, amyotrophic lateral sclerosis, pain, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, lung emphysema, glomerulonephritis, irritable bowel syndrome, psoriasis, atopic dermatitis, Crohn's disease, ulcerative colitis, diabetes mellitus, osteoporosis, and ischemic heart disease, comprising administering to a subject a pharmaceutically active amount of a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof.

13. A method for the treatment of a disease selected from spinal cord injury, stroke, Alzheimer's disease, epilepsy, amyotrophic lateral sclerosis, pain, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, lung emphysema, glomerulonephritis, irritable bowel syndrome, psoriasis, atopic dermatitis, Crohn's disease, ulcerative colitis, diabetes mellitus, osteoporosis, and ischemic heart disease, comprising administering to a subject a pharmaceutically active amount of a compound of formula (I) according to claim 9 or a pharmaceutically acceptable salt thereof.

14. The compound of formula (I) according to claim 2 , wherein

R 2 represents hydrogen and R 3 represents heterocyclyl;

or a salt of such a compound.

15. The compound of formula (I) according to claim 2 , wherein

R 2 and R 3 form, together with the carbon atom to which they are attached, a 6-membered saturated carbocyclic ring which is unsubstituted or di-substituted with fluoro;

or a salt of such a compound.

16. The compound of formula (I) according to claim 2 , wherein

R 4 represents a 6-membered heteroaryl group, which group is unsubstituted or mono-substituted with methyl, trifluoromethyl or chloro;

or a salt of such a compound.

17. The method of claim 12 , wherein the disease is selected from spinal cord injury, Alzheimer's disease, amyotrophic lateral sclerosis, pain, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, lung emphysema, glomerulonephritis, irritable bowel syndrome, psoriasis, atopic dermatitis, Crohn's disease, ulcerative colitis, diabetes mellitus, and osteoporosis.