Muscarinic acetylcholine receptor antagonists

1. A compound of formula (I)

wherein:

R1 is

R2 and R3 are independently selected from the group consisting of

F, G, H, K and L are independently selected from the group consisting of hydrogen, halogen, C 1-4 alkyl, halosubstituted C 1-4 alkyl, hydroxy substituted alkyl, and C 1-4 alkoxy;

R 4 and R 5 are independently selected from the group consisting of hydrogen, halogen, C1-4 alkyl, aryl, C1-4 alkyl aryl, cyano, nitro, (CR7R7)pORb and (CR7R7)pNRbRb;

R6 is selected from the group consisting of hydrogen, C1-4 alkyl;

m is an integer having a value of 1 to 15;

t is 0 or an integer having a value of 1 to 5;

p is 0 or an integer having a value of 1 to 4;

Rb is selected from the group consisting of hydrogen, C1-4 alkyl, aryl and C1-4 alkyl aryl;

R7 is selected from the group consisting of hydrogen, C1-4 alkyl, halosubstituted C1-4 alkyl, and hydroxy substituted C1-4 alkyl; and

X — is a pharmaceutically acceptable anion.

2. A compound according to claim 1

wherein

m is an integer having a value of 1 to 5;

t is 0, 1 or 2;

p is 0, 1 or 2;

R6 is selected from the group consisting of hydrogen and C1-4 alkyl;

Rb is selected from the group consisting of hydrogen, C1-4 alkyl and aryl C1-4 alkyl;

R7 is selected from the group consisting of hydrogen and C1-4 alkyl; and

X — is a pharmaceutically acceptable anion selected from the group consisting of chloride, bromide, iodide, hydroxide, sulfate, nitrate, phosphate, acetate, trifluoroacetate, fumarate, citrate, tartrate, oxalate, succinate, mandelate, methanesulfonate and p-tlouenesulfonate.

3. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier thereof.

4. The compound according to claim 1 wherein X — is selected from the group consisting of chloride, bromide, iodide, hydroxide, sulfate, nitrate, phosphate, acetate, trifluoroacetate, fumarate, citrate, tartrate, oxalate, succinate, mandelate, methanesulfonate and p-toluenesulfonate.

5. The compound according to claim 1 wherein R2 and R3 are both independently selected from

6. The compound according to claim 5 wherein F, G, H, K and L are hydrogen.

7. The compound according to claim 1 wherein R2 and R3 are both independently selected from

8. The compound according to claim 7 wherein F, G and H are hydrogen.

9. The compound according to claim 2 wherein R2 and R3 are both independently selected from

10. The compound according to claim 9 wherein F, G, H, K and L are hydrogen.

11. The compound according to claim 2 wherein R2 and R3 are both independently selected from

12. The compound according to claim 11 wherein F, G and H are hydrogen.

13. The compound according to claim 2 wherein F, G, H, K and L are hydrogen.

14. The compound according to claim 1 wherein R4 and R5 are both hydrogen.

15. The compound according to claim 2 wherein R4 and R5 are both hydrogen.

16. The compound according to claim 10 wherein R4 and R5 are both hydrogen.

17. The compound according to claim 1 wherein m is 2, 3 or 4.

18. The compound according to claim 2 wherein m is 2, 3 or 4.

19. The compound according to claim 10 wherein m is 2, 3 or 4.

20. The compound according to claim 1 wherein t is 0 or 1.

21. The compound according to claim 2 wherein t is 0 or 1.

22. The compound according to claim 10 wherein t is 0 or 1.

23. The compound according to claim 19 wherein t is 0 or 1.

24. The compound according to claim 1 wherein m is 2 and t is 1.

25. The compound according to claim 2 wherein m is 2 and t is 1.

26. The compound according to claim 10 wherein m is 2 and t is 1.

27. The compound according to claim 1 wherein R2 and R3 are both phenyl, R4 and R5 are both hydrogen, m is 2 and t is 1.

28. The compound according to claim 1 wherein R6 is hydrogen.

29. The compound according to claim 2 wherein R6 is hydrogen.

30. The compound according to claim 10 wherein R6 is hydrogen.

31. The compound according to claim 1 wherein F, G, H, K and L are independently selected from the group consisting of hydrogen, halogen, methyl and or methoxy.

32. The compound according to claim 2 wherein F, G, H, K and L are independently selected from the group consisting of hydrogen, halogen, methyl and or methoxy.

33. The compound according to claim 1 wherein p is 0.

34. The compound according to claim 2 wherein p is 0.

35. The compound according to claim 1 wherein R7 is hydrogen.

36. The compound according to claim 2 wherein R7 is hydrogen.

37. The pharmaceutically acceptable anion according to claim 1 which is bromide.

38. The pharmaceutically acceptable anion according to claim 1 which is iodide.

39. The pharmaceutically acceptable anion according to claim 2 which is bromide.

40. The pharmaceutically acceptable anion according to claim 2 which is iodide.

41. The compound according to claim 1 which is:

4-[hydroxy(diphenyl)methyl]-1-[2-(phenyloxy)ethyl]-1-azoniabicyclo [2.2.2]octane bromide;

4-[hydroxy(diphenyl)methyl]-1-[3-(phenyloxy)propyl]-1-azoniabicyclo[2.2.2]octane bromide;

4-[hydroxy(di-2-thienyl)methyl]-1-[2-(phenyloxy)ethyl]-1-azoniabicyclo[2.2.2]octane bromide;

4-[hydroxy(di-2-thienyl)methyl]-1-[3-(phenyloxy)propyl]-1-azoniabicyclo[2.2.2]octane bromide;

4-[hydroxy(diphenyl)methyl]-1-[4-(phenyloxy)butyl]-1-azoniabicyclo[2.2.2]octane bromide;

4-[hydroxy(diphenyl)methyl]-1-{4-[(phenylmethyl)oxy]butyl}-1-azoniabicyclo[2.2.2]octane bromide;

4-[hydroxy(diphenyl)methyl]-1-{3-[(phenylmethyl)oxy]propyl}-1-azoniabicyclo[2.2.2]octane bromide;

1-{2-[(2,4-dibromophenyl)oxy]ethyl}-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;

4-[hydroxy(di-3-thienyl)methyl]-1-[2-(phenyloxy)ethyl]-1-azoniabicyclo[2.2.2]octane bromide;

4-[hydroxy(di-3-thienyl)methyl]-1-[3-(phenyloxy)propyl]-1-azoniabicyclo[2.2.2]octane bromide;

4-[hydroxy(diphenyl)methyl]-1-(3-{[2-(methyloxy)phenyl]oxy}propyl)-1-azoniabicyclo[2.2.2]octane bromide;

4-[hydroxy(diphenyl)methyl]-1-{3-[2-hydroxyphenyl)oxy]propyl}-1-azoniabicyclo[2.2.2]octane bromide;

1-{3-[(3-chlorophenyl)oxy]propyl}-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;

1-{3-[(4-bromophenyl)oxy]propyl}-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;

4-[hydroxy(diphenyl)methyl]-1-{3-[(4-nitrophenyl)oxy]propyl}-1-azoniabicyclo[2.2.2]octane bromide;

1-{3-[(2-bromophenyl)oxy]propyl}-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;

4-[hydroxy(diphenyl)methyl]-1-(3-{[4-(methyloxy)phenyl]oxy}propyl)-1-azoniabicyclo[2.2.2]octane bromide;

4-[hydroxy(di-2-naphthalenyl)methyl]-1-[3-(phenyloxy)propyl]-1-azoniabicyclo[2.2.2]octane bromide;

4-[hydroxy(di-2-naphthalcnyl)methyl]-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide;

1-{3-[(2-fluorophenyl)oxy]propyl}-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;

1-{3-[(3-fluorophenyl)oxy]propyl}-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;

1-{3-[(4-fluorophenyl)oxy]propyl}-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;

1-[3-(3-biphenylyloxy)propyl]-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;

1-[3-(4-biphenylyloxy)propyl]-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;

4-[hydroxy(diphenyl)methyl]-1-{3-[(3-nitrophenyl)oxy]propyl}-1-azoniabicyclo[2.2.2]octane bromide;

4-[hydroxy(diphenyl)methyl]-1-{3-[(2-methylphenyl)oxy]propyl}-1-azoniabicyclo[2.2.2]octane bromide;

1-(3-{[3-(diethylamino)phenyl]oxy}propyl)-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;

4-[hydroxy(diphenyl)methyl]-1-[2-({[3 -(methyloxy)phenyl]methyl}oxy)ethyl]-1-azoniabicyclo[2.2.2]octane bromide;

1-[2-( {[4-(1,1-dimethylethyl)phenyl]methyl}oxy)ethyl]-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;

1-(2-{[(4-fluorophenyl)methyl]oxy}ethyl)-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;

1-(2-{[(4-chlorophenyl)methyl]oxy}ethyl)-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;

1-(2-{[(4-bromophenyl)methyl]oxy}ethyl)-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;

1-(2-{[(4-cyanophenyl)methyl]oxy}ethyl)-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;

4-[hydroxy(diphenyl)methyl]-1-{2-[(2-naphthalenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide;

1-{3-[(4-cyanophenyl)oxy]propyl}-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;

4-[hydroxy(diphenyl)methyl]-1-{2-[(1 -methyl-1-phenylethyl)oxy]ethyl}-1-azoniabicyclo [2.2.2]octane bromide; or

1-(2-{[(3-fluorophenyl)methyl]oxy}ethyl)-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide.

42. The compound according to claim 1 which is;

4-[bis(4-fluorophenyl)(hydroxy)methyl]-1-[3-(phenyloxy)propyl]-1-azoniabicyclo[2.2.2]octane bromide;

4-[bis(4-fluorophenyl)(hydroxy)methyl]-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide;

4-(hydroxy {bis[3-(methyloxy)phenyl]}methyl)-1-[3-(phenyloxy)propyl]-1-azoniabicyclo[2.2.2]octane bromide;

4-(hydroxy {bis[3-(methyloxy)phenyl]}methyl)-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide;

4-(hydroxy {bis[4-(methyloxy)phenyl]}methyl)-1-[3-(phenyloxy)propyl]-1-azoniabicyclo[2.2.2]octane bromide;

4-(hydroxy {bis[4-(methyloxy)phenyl]}methyl)-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide;

4-[bis(3-fluorophenyl)(hydroxy)methyl]-1-[3-(phenyloxy)propyl]-1-azoniabicyclo[2.2.2]octane bromide;

4-[bis(3-fluorophenyl)(hydroxy)methyl]-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide;

4-{hydroxy[bis(3-methylphenyl)]methyl}-1-[3-(phenyloxy)propyl]-1-azoniabicyclo[2.2.2]octane bromide;

4-{hydroxy[bis(3-methylphenyl)]methyl}-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide;

4-{hydroxy[bis(4-methylphenyl)]methyl}-1-[3-(phenyloxy)propyl]-1-azoniabicyclo[2.2.2]octane bromide; or

4-{hydroxy[bis(4-methylphenyl)]methyl}-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide.

43. A pharmaceutical composition comprising a compound according to claim 41 and a pharmaceutically acceptable carrier thereof.

44. A pharmaceutical composition comprising a compound according to claim 42 and a pharmaceutically acceptable carrier thereof.

45. A pharmaceutical composition comprising a compound according to claim 42 and a pharmaceutically acceptable carrier thereof.

46. A pharmaceutical composition according to claim 3 in a form suitable for administration by oral or nasal inhalation.

47. A pharmaceutical composition according to claim 46 wherein the form is suitable for administration by inhalation via a medicament dispenser selected from a reservoir dry powder inhaler, a multi-dose dry powder inhaler, or a metered dose inhaler.

48. A pharmaceutical composition according to claim 3 which is a dry powder composition.

49. A pharmaceutical composition according to claim 3 wherein the pharmaceutically acceptable carrier is lactose.