Oxazolone and pyrrolidinone-substituted pryidine amides as P2X

1. A compound of formula I:

or a pharmaceutically acceptable salt thereof,

wherein:

R 1 is:

C 1-6 alkyl; or

halo;

R 2 is:

C 3-6 cycloalkyl;

C 1-6 alkoxy-C 1-6 alkyl;

hydroxy-C 1-6 alkyl; or

heteroaryl-C 1-6 alkyl wherein the heteroaryl portion thereof is optionally substituted once or twice with C 1-6 alkyl;

R 3 is:

hydrogen;

halo;

C 1-6 alkyl; or

C 1-6 alkoxy-carbonyl;

R 4 is:

hydrogen;

halo; or

C 1-6 alkyl;

or R 3 and R 4 together with the atoms to which they are attached may form a fused 6-membered aromatic ring that optionally includes one or two nitrogens;

or R 3 and R 4 together with the atom to which they are attached may form C 3-6 cycloalkyl;

R 5 , R 6 and R 7 each independently is fluoro or hydrogen;

X is: —N; and

Y is: —O—; —CHR b —; or —NR c —; wherein R b and R c each independently is hydrogen or C 1-6 alkyl.

2. The compound of claim 1 , wherein R 5 , R 6 and R 7 are hydrogen.

3. The compound of claim 2 , wherein R 1 is methyl.

4. The compound of claim 2 , wherein R 2 is: cyclopropyl; 2-methoxy-1-methyl-ethyl; 2-hydroxy-1-methyl-ethyl; 5-methylpyrazin-2-yl-methyl; 1-pyrazin-2-yl-ethyl; pyrimidin-5-yl-methyl; 6-methyl-pyridazin-3-yl-methyl; pyridazin-3-yl-methyl; 5-methyl-pyrimidin-2-yl-methyl; or 2-methyl-pyrimidin-5-yl-methyl.

5. The compound of claim 2 , wherein R 2 is 2-hydroxy-1-methyl-ethyl; 5-methylpyrazin-2-yl-methyl; or 1-pyrazin-2-yl-ethyl.

6. The compound of claim 2 , wherein R 3 is C 1-6 alkyl.

7. The compound of claim 2 , wherein R 3 is ethyl or isopropyl.

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

9. The compound of claim 2 , wherein R 3 and R 4 together with the atoms to which they are attached form a fused phenyl ring.

10. The compound of claim 2 , wherein Y is —O—.

11. The compound of claim 2 , wherein Y is —CHR b —.

12. The compound of claim 2 , wherein Y is —NR c —.

13. A pharmaceutical composition comprising:

(a) a pharmaceutically acceptable carrier; and

(b) a compound of claim 1 .

14. A compound of formula III:

wherein:

n is 0, 1 or 2;

X is: —N;

Y is: —O—; —CH 2 — or —NH—;

R 1 is:

C 1-6 alkyl; or

halo;

R 2 is:

C 3-6 cycloalkyl;

C 1-6 alkoxy-C 1-6 alkyl;

hydroxy-C 1-6 alkyl; or

heteroaryl-C 1-6 alkyl wherein the heteroaryl portion thereof is optionally substituted once or twice with C 1-6 alkyl; and

R 8 is:

C 1-6 alkyl;

C 1-6 alkoxy;

C 1-6 alkyl-sulfonyl;

halo-C 1-6 alkyl; or

halo.

15. The compound of claim 14 , wherein R 1 is methyl.

16. The compound of claim 15 , wherein Y is —O—.

17. A compound selected from:

N-(5-Methyl-pyrazin-2-ylmethyl)-3-(5-methyl-pyridin-2-yl)-5-(2-oxo-benzooxazol-3-yl)-benzamide;

3-(5-Methyl-pyridin-2-yl)-5-(2-oxo-benzooxazol-3-yl)-N-(1-pyrazin-2-yl-ethyl)-benzamide

N—((S)-2-Hydroxy-1-methyl-ethyl)-3-(5-methyl-pyridin-2-yl)-5-(2-oxo-benzooxazol-3-yl)-benzamide;

3-(5-Methyl-pyridin-2-yl)-5-(2-oxo-2,3-dihydro-benzoimidazol-1-yl)-N-(1-pyrazin-2-yl-ethyl)-benzamide;

N-(5-Methyl-pyrazin-2-ylmethyl)-3-(5-methyl-pyridin-2-yl)-5-(2-oxo-2,3-dihydro-indol-1-yl)-benzamide;

3-(5-Methyl-pyridin-2-yl)-5-(2-oxo-2,3-dihydro-indol-1-yl)-N-(1-pyrazin-2-yl-ethyl)-benzamide;

3-((R)-4-Isopropyl-2-oxo-oxazolidin-3-yl)-N—((R)-2-methoxy-1-methyl-ethyl)-5-(5-methyl-pyridin-2-yl)-benzamide;

N-Cyclopropyl-3-((R)-4-isopropyl-2-oxo-oxazolidin-3-yl)-5-(5-methyl-pyridin-2-yl)-benzamide;

N—((S)-2-Hydroxy-1-methyl-ethyl)-3-((R)-4-isopropyl-2-oxo-oxazolidin-3-yl)-5-(5-methyl-pyridin-2-yl)-benzamide;

3-((R)-4-Isopropyl-2-oxo-oxazolidin-3-yl)-5-(5-methyl-pyridin-2-yl)-N-(1-pyrazin-2-yl-ethyl)-benzamide;

3-((R)-4-Isopropyl-2-oxo-oxazolidin-3-yl)-N-(5-methyl-pyrazin-2-ylmethyl)-5-(5-methyl-pyridin-2-yl)-benzamide;

3-(5-Methyl-pyridin-2-yl)-5-(2-oxo-benzooxazol-3-yl)-N-pyrimidin-5-ylmethyl-benzamide;

N-(6-Methyl-pyridazin-3-ylmethyl)-3-(5-methyl-pyridin-2-yl)-5-(2-oxo-benzooxazol-3-yl)-benzamide;

3-(5-Methyl-pyridin-2-yl)-5-(2-oxo-benzooxazol-3-yl)-N-pyridazin-3-ylmethyl-benzamide;

3-((R)-4-Methyl-2-oxo-oxazolidin-3-yl)-5-(5-methyl-pyridin-2-yl)-N-(1-pyrazin-2-yl-ethyl)-benzamide;

3-((R)-4-Methyl-2-oxo-oxazolidin-3-yl)-N-(5-methyl-pyrazin-2-ylmethyl)-5-(5-methyl-pyridin-2-yl)-benzamide;

3-(4-Ethyl-2-oxo-oxazolidin-3-yl)-N—((S)-2-hydroxy-1-methyl-ethyl)-5-(5-methyl-pyridin-2-yl)-benzamide;

3-(4-Ethyl-2-oxo-oxazolidin-3-yl)-5-(5-methyl-pyridin-2-yl)-N-(1-pyrazin-2-yl-ethyl)-benzamide;

3-(4-Ethyl-2-oxo-oxazolidin-3-yl)-N-(5-methyl-pyrazin-2-ylmethyl)-5-(5-methyl-pyridin-2-yl)-benzamide;

3-(4,4-Dimethyl-2-oxo-oxazolidin-3-yl)-5-(5-methyl-pyridin-2-yl)-N-(1-pyrazin-2-yl-ethyl)-benzamide;

3-(4,4-Dimethyl-2-oxo-oxazolidin-3-yl)-N-(5-methyl-pyrazin-2-ylmethyl)-5-(5-methyl-pyridin-2-yl)-benzamide;

N—((S)-2-Hydroxy-1-methyl-ethyl)-3-(5-methyl-pyridin-2-yl)-5-((R)-2-oxo-4-propyl-oxazolidin-3-yl)-benzamide;

3-(5-Methyl-pyridin-2-yl)-5-((R)-2-oxo-4-propyl-oxazolidin-3-yl)-N-(1-pyrazin-2-yl-ethyl)-benzamide;

N-(5-Methyl-pyrazin-2-ylmethyl)-3-(5-methyl-pyridin-2-yl)-5-((R)-2-oxo-4-propyl-oxazolidin-3-yl)-benzamide;

3-(4,4-Dimethyl-2-oxo-oxazolidin-3-yl)-N—((S)-2-hydroxy-1-methyl-ethyl)-5-(5-methyl-pyridin-2-yl)-benzamide;

N—((S)-2-Hydroxy-1-methyl-ethyl)-3-(2-methyl-5-oxo-pyrrolidin-1-yl)-5-(5-methyl-pyridin-2-yl)-benzamide;

3-(2-Methyl-5-oxo-pyrrolidin-1-yl)-5-(5-methyl-pyridin-2-yl)-N-(1-pyrazin-2-yl-ethyl)-benzamide;

3-(2-Methyl-5-oxo-pyrrolidin-1-yl)-N-(5-methyl-pyrazin-2-ylmethyl)-5-(5-methyl-pyridin-2-yl)-benzamide;

N-(5-Methyl-pyrazin-2-ylmethyl)-3-(5-methyl-pyridin-2-yl)-5-(5-oxo-6-oxa-4-aza-spiro[2,4]hept-4-yl)-benzamide;

N-(5-Methyl-pyrazin-2-ylmethyl)-3-(5-methyl-pyridin-2-yl)-5-(8-oxo-7,8-dihydro-purin-9-yl)-benzamide;

3-(4,4-Dimethyl-2-oxo-oxazolidin-3-yl)-N-(6-methyl-pyridazin-3-ylmethyl)-5-(5-methyl-pyridin-2-yl)-benzamide;

3-(5-Methyl-pyridin-2-yl)-N-(5-methyl-pyrimidin-2-ylmethyl)-5-(2-oxo-benzooxazol-3-yl)-benzamide; and

3-(5-Methyl-pyridin-2-yl)-N-(2-methyl-pyrimidin-5-ylmethyl)-5-(2-oxo-benzooxazol-3-yl)-benzamide;

or a pharmaceutically acceptable salt thereof.