Dihydropyridone ureas as P2X

1. A compound of formula I:

or pharmaceutically acceptable salts thereof,

wherein:

m is 0 or 1;

n is 0 or 1;

R 1 is:

optionally substituted aryl;

optionally substituted heteroaryl; or

adamantyl;

R 2 is:

optionally substituted aryl;

optionally substituted heteroaryl;

C 3-6 cycloalkyl;

C 1-6 alkyl; or

C 3-6 branched alkyl; and

R 3 , R 4 and R 5 each independently is:

hydrogen; or

C 1-6 alkyl.

2. The compound of claim 1 , wherein m is 0.

3. The compound of claim 2 , wherein n is 0.

4. The compound of claim 3 , wherein R 3 , R 4 and R 5 are hydrogen.

5. The compound of claim 4 , wherein R 1 is optionally substituted phenyl.

6. The compound of claim 5 , wherein R 1 is phenyl substituted one, two, three or four times with a substituent or substituents each independently selected from: halo; C 1-6 alkyl; C 1-6 alkoxy; halo-C 1-6 alkyl; halo-C 1-6 alkoxy; C 1-6 alkylsulfonyl; C 1-6 alkylsulfanyl; C 1-6 alkylsulfinyl; phenylsulfonyl wherein the phenyl portion is optionally substituted with C 1-6 alkyl; nitrile; hydroxy; C 1-6 alkylcarbonyl; aminocarbonyl; C 1-6 alkoxycarbonyl; C 1-6 alkoxycarbonyl-C 1-6 alkoxy; hydroxycarbonyl; hydroxycarbonyl-C 1-6 alkoxy; C 1-6 alkylaminocarbonyl-C 1-6 alkoxy; C 1-6 alkoxy-C 1-6 alkoxy; hydroxy-C 1-6 alkoxy; C 1-6 alkylamino-C 1-6 alkoxy; C 1-6 alkylsulfony-C 1-6 alkoxy; hydroxy-C 1-6 alkyl; C 3-6 cycloalkyl-C 1-6 alkoxy; amino; amino-C 1-6 alkyl; C 1-6 alkenyl; C 1-6 alkynyl; morpholinyl; morpholinyl-C 1-6 alkyl; piperazinyl; piperidinyloxy; aminocarbonyl-C 1-6 alkoxy; C 1-6 alkoxyamino-C 1-6 alkyl; hydroxy-C 1-6 alkylamino-C 1-6 alkyl; C 1-6 alkoxycarbonylamino-C 1-6 alkyl; C 1-6 alkylcarbonylamino-C 1-6 alkyl; C 1-6 alkylaminocarbonyl; C 1-6 alkoxycarbonylC 1-6 alkyl; C 1-6 alkylaminocarbonyl-C 1-6 alkyl; C 1-6 alkylamino-C 1-6 alkyl; hydroxycarbonyl-C 1-6 alkyl; or nitro; or two adjacent substituents may form a C 1-2 alkylenedioxy or halo-C 1-2 alkylenedioxy.

7. The compound of claim 5 , wherein R 1 is phenyl substituted one, two, three or four times with a substituent or substituents each independently selected from: fluoro; chloro; bromo; iodo; methyl; ethyl; methoxy; ethoxy; trifluoromethyl; difluoromethoxy; trifluoromethoxy; methanesulfonyl; methanesulfanyl; methanesulfinyl; toluenesulfonyl; nitrile; acetyl; aminocarbonyl; methoxycarbonyl; methoxycarbonylmethoxy; carboxy; hydroxycarbonylmethoxy; methylaminocarbonylmethoxy; methoxyethoxy; hydroxyethoxy; methylaminoethoxy; methanesulfonylpropyloxy; hydroxymethyl; hydroxyethyl; cyclopropylmethoxy; amino; or nitro; morpholinyl; N,N-dimethylaminocarbonylmethoxy; boc-piperazinyl; N-(2-methoxyethyl)-N-methylaminomethyl; N,N-dimethylaminomethyl; aminomethyl; boc-aminomethyl; methylcarbonylaminomethyl; N,N-di-(2-hydroxyethyl)-aminomethyl; morpholinylmethyl; 2-hydroxy-1-hydroxymethyl-ethyl; methylaminocarbonyl; piperidinyloxy; tert-butoxycarbonylmethyl; N,N-dimethylaminocarbonylmethyl; n-propyl; isopropyl; hydroxycarbonylmethyl; hydroxypropoxy; or two adjacent substituents may form methylenedioxy, ethylenedioxy or difluoromethylenedioxy.

8. The compound of claim 5 , wherein R 1 is phenyl substituted one, two, three or four times with a substituent or substituents each independently selected from: halo; C 1-6 alkyl; C 1-6 alkoxy; halo-C 1-6 alkyl; halo-C 1-6 alkoxy; C 1-6 alkylsulfonyl; nitrile; C 1-6 alkoxy-C 1-6 alkoxy; hydroxy-C 1-6 alkoxy; C 1-6 alkylsulfonyl-C 1-6 alkoxy; hydroxy-C 1-6 alkyl; hydroxy-C 1-6 alkylamino; C 1-2 alkylenedioxy; or C 3-6 cycloalkyl-C 1-6 alkoxy.

9. The compound of claim 5 , wherein R 1 is phenyl substituted one, two, three or four times with a substituent or substituents each independently selected from: fluoro; chloro; bromo; iodo; methyl; ethyl; methoxy; ethoxy; trifluoromethyl; difluoromethoxy; methanesulfonyl; nitrile; methoxyethoxy; hydroxyethoxy; hydroxymethyl; hydroxyethyl; hydroxypropoxy; methylenedioxy; or ethylenedioxy.

10. The compound of claim 5 , wherein R 1 is phenyl optionally substituted one, two or three times with a substituent or substituents each independently selected from: fluoro; chloro; bromo; methyl; ethyl; methoxy; ethoxy; trifluoromethyl; difluoromethoxy; nitrile; methoxyethoxy; hydroxyethoxy; hydroxymethyl; hydroxyethyl; or cyclopropylmethoxy.

11. The compound of claim 5 , wherein R 2 is optionally substituted phenyl.

12. The compound of claim 5 , wherein R 2 is phenyl optionally substituted one, two or three times with a substituent or substituents each independently selected from: fluoro; chloro; bromo; methyl; ethyl; methoxy; ethoxy; trifluoromethyl; difluoromethoxy; nitrile; methoxyethoxy; hydroxyethoxy; hydroxymethyl; hydroxyethyl; or cyclopropylmethoxy.

13. The compound of claim 5 , wherein R 2 is phenyl substituted once or twice with a substituent or substituents each independently selected from: fluoro; chloro; methyl; methoxy; or nitrile.

14. The compound of claim 5 , wherein R 2 is phenyl substituted once or twice with fluoro.

15. The compound of claim 1 , wherein said compound is of formula II:

wherein:

p is from 0 to 3;

R 6 , R 7 , R 8 , R 9 and R 10 each independently is: hydrogen; halo; C 1-6 alkyl; C 1-6 alkoxy; halo-C 1-6 alkyl; halo-C 1-6 alkoxy; C 1-6 alkylsulfonyl; C 1-6 alkylsulfanyl; C 1-6 alkylsulfinyl; phenylsulfonyl wherein the phenyl portion is optionally substituted with C 1-6 alkyl; nitrile; hydroxy; alkylcarbonyl; aminocarbonyl; alkoxycarbonyl; alkoxycarbonylalkoxy; hydroxycarbonyl; hydroxycarbonylalkoxy; alkylaminocarbonylalkoxy; alkoxyalkoxy; hydroxyalkoxy; alkylaminoalkoxy; alkylsulfonylalkoxy; hydroxyalkyl; C 3-6 cycloalkyl-C 1-6 alkoxy; amino; aminoalkyl; or nitro; or two adjacent substituents may form a C 1-2 alkylenedioxy or halo-C 1-2 alkylenedioxy; and

each R 11 independently is: halo; C 1-6 alkyl; C 1-6 alkoxy; halo-C 1-6 alkyl; halo-C 1-6 alkoxy; C 1-6 alkylsulfonyl; or nitrile.

16. The compound of claim 15 , wherein at least two of R 6 , R 7 , R 8 , R 9 and R 10 are not hydrogen.

17. The compound of claim 15 , wherein R 6 , R 7 , R 8 , R 9 and R 10 each independently is: hydrogen; fluoro; chloro; bromo; iodo; methyl; ethyl; methoxy; ethoxy; trifluoromethyl; difluoromethoxy; trifluoromethoxy; methanesulfonyl; methanesulfanyl; methanesulfinyl; toluenesulfonyl; nitrile; acetyl; aminocarbonyl; methoxycarbonyl; methoxycarbonylmethoxy; carboxy; hydroxycarbonylmethoxy; methylaminocarbonylmethoxy; methoxyethoxy; hydroxyethoxy; methylaminoethoxy; methanesulfonylpropyloxy; hydroxymethyl; hydroxyethyl; cyclopropylmethoxy; amino; or nitro; morpholinyl; N,N-dimethylaminocarbonylmethoxy; boc-piperazinyl; N-(2-methoxyethyl)-N-methylaminomethyl; N,N-dimethylaminomethyl; aminomethyl; boc-aminomethyl; methylcarbonylaminomethyl; N,N-di-(2-hydroxyethyl)-aminomethyl; morpholinylmethyl; 2-hydroxy-1-hydroxymethyl-ethyl; methylaminocarbonyl; piperidinyloxy; tert-butoxycarbonylmethyl; N,N-dimethylaminocarbonylmethyl; n-propyl; isopropyl; hydroxycarbonylmethyl; hydroxypropoxy; or two adjacent substituents may form methylenedioxy, ethylenedioxy or difluoromethylenedioxy.

18. The compound of claim 15 , wherein R 6 , R 7 , R 8 , R 9 and R 10 each independently is: hydrogen; halo; C 1-6 alkyl; C 1-6 alkoxy; halo-C 1-6 alkyl; halo-C 1-6 alkoxy; C 1-6 alkylsulfonyl; nitrile; alkoxyalkoxy; hydroxyalkoxy; alkylsulfonylalkoxy; hydroxyalkyl; or C 3-6 cycloalkyl-C 1-6 alkoxy.

19. The compound of claim 15 , wherein R 6 , R 7 , R 8 , R 9 and R 10 each independently is: hydrogen; fluoro; chloro; bromo; iodo; methyl; ethyl; methoxy; ethoxy; trifluoromethyl; difluoromethoxy; methanesulfonyl; nitrile; methoxyethoxy; hydroxyethoxy; hydroxymethyl; hydroxyethyl; or cyclopropylmethoxy.

20. The compound of claim 15 , wherein R 6 , R 7 , R 8 , R 9 and R 10 each independently is: hydrogen; fluoro; chloro; bromo; methyl; ethyl; methoxy; ethoxy; trifluoromethyl; difluoromethoxy; nitrile; methoxyethoxy; hydroxyethoxy; hydroxymethyl; hydroxyethyl; or cyclopropylmethoxy.

21. The compound of claim 15 , wherein R 7 and R 10 are hydrogen.

22. The compound of claim 21 , wherein R 6 is: hydrogen; halo; or methyl.

23. The compound of claim 22 , wherein R 8 is: hydrogen; methoxy; halo; methyl; or difluoromethoxy.

24. The compound of claim 15 , wherein R 9 is: methoxy; hydrogen; 2-hydroxy-ethoxy; 2-methoxy-ethoxy; 1-hydroxy-ethyl; or cyclopropylmethyl.

25. The compound of claim 15 , wherein p is 0, 1 or 2.

26. The compound of claim 25 , wherein R 11 is halo.

27. The compound of claim 25 , wherein R 11 is fluoro.

28. The compound of claim 15 , wherein said compound is of formula III

wherein R 6 , R 8 , R 9 and R 11 are as recited in claim 15 .

29. A pharmaceutical composition comprising:

(a) a pharmaceutically acceptable carrier; and

(b) a compound of claim 1 .

30. A method for treating arthritis, said method comprising administering to a subject in need thereof an effective amount of a compound of claim 1 .