Granted Patent B2

US 6,846,834 · App. 10/004,287 · Granted Jan 25, 2005

Abstract

Claims (114)

1. A compound having the formula:

wherein

W is N;

X is CH;

Y is selected from the group consisting of O, S and N(R);

wherein R is selected from the group consisting of H, CN, NO 2 , (C 1 -C 10 )alkyl, (C 3 -C 10 )cycloalkyl, (C 4 -C 10 )cycloalkyl-alkyl, (C 3 -C 10 )alkenyl and (C 2 -C 10 )alkynyl;

Z is selected from the group consisting of H, (C 1 -C 10 )alkyl, (C 3 -C 10 )cycloalkyl, (C 4 -C 10 )cycloalkyl-alkyl, (C 2 -C 10 )alkenyl, (C 2 -C 10 )alkynyl and NR 2 R 3 ;

R 1 , R 2 and R 3 are independently selected from the group consisting of H, (C 1 -C 10 )alkyl, (C 3 -C 10 )alkenyl, (C 2 -C 10 )alkynyl, (C 1 -C 10 )heteroalkyl, (C 3 -C 10 )cycloalkyl, (C 4 -C 10 )cycloalkyl-alkyl, (C 3 -C 10 )cycloheteroalkyl-alkyl, (C 3 -C 10 )cycloheteroalkyl, aryl, aryl(C 1 -C 4 )alkyl, aryl(C 1 -C 4 )heteroalkyl, heteroaryl(C 1 -C 4 )alkyl, heteroaryl(C 1 -C 4 )heteroalkyl and perfluoro(C 1 -C 6 )alkyl; and wherein when Z is NR 2 R 3 , R 2 and R 3 can be combined to form a 5- to 7-membered heterocyclyl ring;

R 4 is selected from the group consisting of H, (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 4 -C 7 )cycloalkyl-alkyl, (C 2 -C 6 )alkenyl and (C 2 -C 6 )alkynyl;

A is a substituted or unsubstituted 6-membered fused carbocyclic or heterocyclic aromatic ring system, wherein the heterocyclic aromatic ring system contains 1-2 N atoms; and

B is a substituted or unsubstituted five- or six-membered ring which is aromatic, containing at least one nitrogen atom, and from 0 to 3 additional heteroatoms, wherein the B ring substituents are selected from the group consisting of halogen, CF 3 , CF 3 O, (C 1 -C 6 )alkyl, perfluoro(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )heteroalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )thioalkoxy, amino, (C 1 -C 6 )alkylamino, di(C 1 -C 6 )alkylamino, (C 3 -C 10 )cycloalkyl, (C 4 -C 10 )cycloalkyl-alkyl, (C 3 -C 10 )cycloheteroalkyl, cyano, nitro, sulfonamido, (C 1 -C 6 )acyl, (C 1 -C 6 )acylamino, (C 1 -C 6 )alkoxycarbonyl, (C 1 -C 6 )alkoxycarbonyl(C 1 -C 6 )alkyl, carboxamido and (C 1 -C 6 )heteroalkoxyl;

or pharmaceutically acceptable salts thereof.

2. A compound of claim 1 , wherein Y is selected from the group consisting of O and S.

3. A compound of claim 1 , wherein Y is O.

4. A compound of claim 1 , wherein Y is S.

5. A compound of claim 1 , wherein Z is NR 2 R 3 .

6. A compound of claim 2 , wherein R 4 is H.

7. A compound of claim 1 , wherein A is selected from the group consisting of:

wherein

R 5 , R 6 , R 7 and R 8 are independently selected from the group consisting of H, halogen, CF 3 , (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )heteroalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )thioalkoxy, amino, (C 1 -C 6 )alkylamino, di(C 1 -C 6 )alkylamino, (C 3 -C 10 )cycloalkyl, (C 4 -C 10 )cycloalkyl-alkyl, (C 3 -C 10 )cycloheteroalkyl, (C 3 -C 10 )cycloheteroalkyl-alkyl, cyano, nitro, (C 1 -C 6 )acyl, (C 1 -C 6 )acylamino, (C 1 -C 6 )alkoxycarbonyl, (C 1 -C 6 )alkoxycarbonyl (C 1 -C 6 )alkyl, CONH 2 , CO—NH—(C 1 -C 6 )alkyl, CO—N[(C 1 -C 6 )alkyl] 2 , SO 2 NH 2 , SO 2 NH—(C 1 -C 6 )alkyl, SO 2 N—[(C 1 -C 6 )alkyl] 2 and (C 1 -C 6 )heteroalkoxy; or two adjacent R groups selected from R 5 , R 6 , R 7 and R 8 , can be linked together to form a new 5- or 6-membered carbocyclic or heterocyclic ring.

8. A compound of claim 7 , wherein Y is O or S; and A is selected from the group consisting of:

9. A compound of claim 1 , wherein B contains a nitrogen atom at a position two atoms away from the atom attaching B to the remainder of the molecule.

10. A compound of claim 1 , wherein B contains a nitrogen atom at the point of attachment of B to the remainder of the molecule.

11. A compound of claim 1 , wherein B is selected from the group consisting of 1-methylimidazol-5-yl, 1-(trifluoromethyl)imidazol-5-yl, 5-methylimidazol-1-yl, 5-(trifluoromethyl)imidazol-1-yl, thiazol-5-yl, imidazol-1-yl, 1-methyl-1,3,4-triazolyl, and 4-methyl-1,2,4-triazol-3-yl.

12. A compound of claim 1 , wherein B is selected from the group consisting of substituted or unsubstituted imidazolyl, substituted or unsubstituted thiazolyl and substituted or unsubstituted triazolyl.

13. A compound of claim 8 , wherein B contains a nitrogen atom at a position two atoms away from the atom attaching B to the remainder of the molecule.

14. A compound of claim 8 , wherein B contains a nitrogen atom at the point of attachment of B to the remainder of the molecule.

15. A compound of claim 8 , wherein B is selected from the group consisting of 1-methylimidazol-5-yl, 1-(trifluoromethyl)imidazol-5-yl, 5-methylimidazol-1-yl, 5-(trifluoromethyl)imidazol-1-yl, thiazol-5-yl, imidazol-1-yl, 1-methyl-1,3,4-triazolyl, and 4-methyl-1,2,4-triazol-3-yl.

16. A compound of claim 8 , wherein B is selected from the group consisting of substituted or unsubstituted imidazolyl, substituted or unsubstituted thiazolyl and substituted or unsubstituted triazolyl.

17. A compound of claim 1 , wherein Y is O or S; Z is H, CH 3 , NH 2 or NHCH 3 ; R 1 is H, (C 1 -C 6 )alkyl, (C 1 -C 10 )heteroalkyl, (C 4 -C 10 )cycloheteroalkyl-alkyl, (C 3 -C 10 )cycloheteroalkyl, aryl(C 1 -C 4 )alkyl, aryl(C 1 -C 4 )heteroalkyl, heteroaryl(C 1 -C 4 )alkyl, heteroaryl(C 1 -C 4 )heteroalkyl, or perfluoro(C 1 -C 6 )alkyl; R 4 is H; A represents

wherein R 6 and R 7 are independently selected from the group consisting of H, halogen, CF 3 , CF 3 O, (C 1 -C 4 )alkyl, (C 2 -C 4 )alkenyl, (C 2 -C 4 )alkynyl, (C 1 -C 4 )heteroalkyl, (C 3 -C 10 )cycloheteroalkyl-alkyl and cyano; and B is a five-membered aromatic ring system containing at least one nitrogen atom.

18. A compound of claim 17 , wherein Y is S.

19. A compound of claim 17 , wherein Z is NR 2 R 3 .

20. A compound of claim 17 , wherein Z is NH 2 .

21. A compound of claim 17 , wherein R 1 is (C 1 -C 6 )alkyl, (C 1 -C 6 )heteroalkyl or (C 3 -C 10 )cycloheteroalkyl-alkyl.

22. A compound of claim 17 , wherein B is a five-membered aromatic ring system containing 1-2 nitrogen atoms and 0-1 sulfur atoms.

23. A compound of claim 22 , wherein B is unsubstituted or substituted by (C 1 -C 3 )alkyl, CF 3 , cyano, or halogen.

24. A compound of claim 17 , wherein Z is NH 2 ; R 6 is selected from the group consisting of H, halogen, CF 3 , CF 3 O, (C 1 -C 4 )alkyl, (C 2 -C 4 )alkenyl, (C 1 -C 4 )heteroalkyl, (C 3 -C 10 )cycloheteroalkyl-alkyl and cyano, wherein the alkyl, alkenyl and heteroalkyl groups optionally bear additional substituents selected from cyano, carboxamido, (C 1 -C 3 )alkylsulfonyl or (C 1 -C 3 )alkoxy; and R 7 is selected from the group consisting of H, halogen, CF 3 , CF 3 O, (C 1 -C 4 )alkyl, (C 2 -C 4 )alkenyl, (C 2 -C 4 )alkynyl, (C 1 -C 4 )heteroalkyl and cyano.

25. A compound of claim 24 , wherein R 6 is selected from the group consisting of CH 2 (CH 2 )[[ m ]] n CN, CH 2 (CH 2 ) n SO 2 CH 3 and CH 2 (CH 2 ) n OCH 3 , wherein the subscript n is an integer from 0 to 2.

26. A compound of claim 24 wherein R 7 is selected from the group consisting of H, halogen, CF 3 and (C 1 -C 4 )alkyl.

27. A compound of claim 24 , wherein R 7 is methyl.

28. A compound of claim 1 , having the formula:

wherein Y is O, S or N—CN; W′ is N(CH 3 ), N(CF 3 ), N(CH 2 CH 3 ), O or S; the subscripts n and n′ are independently integers from 0 to 3; R 7 is H, halogen, CF 3 , CF 3 O, (C 1 -C 4 )alkyl, (C 2 -C 4 )alkenyl, (C 2 -C 4 )alkynyl, (C 1 -C 4 )heteroalkyl or cyano; R 9 is CN, CONH 2 , CO—NH—(C 1 -C 6 )alkyl, CO—N[(C 1 -C 6 )alkyl] 2 , CO—NH—(C 1 -C 6 )heteroalkyl, CO—N[(C 1 -C 6 )heteroalkyl] 2 , S(O) n″ —(C 1 -C 6 )alkyl, S(O) n″ —(C 1 -C 6 )heteroalkyl, heteroaryl, (C 1 -C 6 )alkoxy or (C 3 -C 6 )cycloheteroalkyl, wherein each n″ is independently an integer of 0 to 2; R 10 is NH 2 , NH—(C 1 -C 6 )alkyl, N[(C 1 -C 6 )alkyl] 2 , NH—(C 1 -C 6 )heteroalkyl, N[(C 1 -C 6 )heteroalkyl] 2 , (C 1 -C 6 )heteroalkyl, S(O) n″ —(C 1 -C 6 )alkyl, S(O) n″ —(C 1 -C 6 )heteroalkyl, aryl, heteroaryl, O—(C 1 -C 6 )alkyl, O—(C 1 -C 6 )heteroalkyl or (C 3 -C 8 )cycloheteroalkyl; and R 11 is H, CF 3 , NH 2 , NH—(C 1 -C 6 )alkyl, N[(C 1 -C 6 )alkyl] 2 , halogen or (C 1 -C 3 )alkyl.

29. A compound of claim 28 , wherein Y is O or S; W′ is N—CH 3 ; n is 2; n′ is 1-3; R 9 is cyano, CONH 2 , SO 2 —(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy or (C 3 -C 6 )cycloheteroalkyl; R 10 is NH—(C 1 -C 6 )alkyl, N[(C 1 -C 6 )alkyl] 2 , NH—(C 1 -C 6 )heteroalkyl, N[(C 1 -C 6 )heteroalkyl] 2 , O—(C 1 -C 6 )alkyl, O—(C 1 -C 6 )heteroalkyl, (C 1 -C 6 )alkoxy or (C 3 -C 8 )cycloheteroalkyl; and R 11 is H.

30. A compound of claim 17 , wherein B contains a nitrogen atom at a position two atoms away from the atom attaching B to the remainder of the molecule.

31. A compound of claim 17 , wherein B contains a nitrogen atom at the point of attachment of B to the remainder of the molecule.

32. A compound of claim 17 , wherein B is selected from the group consisting of substituted or unsubstituted imidazolyl, substituted or unsubstituted thiazolyl and substituted or unsubstituted triazolyl.

33. A compound of claim 17 , wherein B is selected from the group consisting of 1-methylimidazol-5-yl, 1-(trifluoromethyl)imidazol-5-yl, 5-methylimidazol-1-yl, 5-(trifluoromethyl)imidazol-1-yl, thiazol-5-yl, imidazol-1-yl, 1-methyl-1,3,4-triazolyl, and 4-methyl-1,2,4-triazol-3-yl.

34. A compound of claim 1 , wherein Y is S; Z is NH 2 and R 1 is (C 1 -C 6 )alkyl.

35. A compound of claim 34 wherein R 1 is methyl.

36. A compound of claim 1 , wherein said compound is selected from the group consisting of:

37. A composition comprising a pharmaceutically acceptable excipient and a compound having the formula:

wherein

W is N;

X is CH;

Y is selected from the group consisting of O, S and N(R);

wherein R is selected from the group consisting of H, CN, NO 2 , (C 1 -C 10 )alkyl, (C 3 -C 10 )cycloalkyl, (C 4 -C 10 )cycloalkyl-alkyl, (C 3 -C 10 )alkenyl and (C 2 -C 10 )alkynyl;

Z is selected from the group consisting of H, (C 1 -C 10 )alkyl, (C 3 -C 10 )cycloalkyl, (C 4 -C 10 )cycloalkyl-alkyl, (C 2 -C 10 )alkenyl, (C 2 -C 10 )alkynyl and NR 2 R 3 ;

R 1 , R 2 and R 3 are independently selected from the group consisting of H, (C 1 -C 10 )alkyl, (C 3 -C 10 )alkenyl, (C 2 -C 10 )alkynyl, (C 2 -C 10 )heteroalkyl, (C 3 -C 10 )cycloalkyl, (C 4 -C 10 )cycloalkyl-alkyl, (C 3 -C 10 )cycloheteroalkyl-alkyl, (C 3 -C 10 )cycloheteroalkyl, aryl, aryl(C 1 -C 4 )alkyl, aryl(C 2 -C 4 )heteroalkyl, heteroaryl(C 2 -C 4 )alkyl, heteroaryl(C 2 -C 4 )heteroalkyl and perfluoro(C 1 -C 6 )alkyl; and wherein when Z is NR 2 R 3 , R 2 and R 3 can be combined to form a 5- to 7-membered ring; and wherein when Y is N(R), R and R 1 are optionally combined to form a 5- to 7-membered ring;

R 4 is selected from the group consisting of H, (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 4 -C 7 )cycloalkyl-alkyl, (C 2 -C 6 )alkenyl and (C 2 -C 6 )alkynyl;

A is a substituted or unsubstituted 6-membered fused carbocyclic or heterocyclic aromatic ring system, wherein the heterocyclic aromatic ring system contains 1-2 N atoms; and

B is a substituted or unsubstituted five- or six-membered ring which is aromatic, containing at least one nitrogen atom, and from 0 to 3 additional heteroatoms, wherein the B ring substituents are selected from the group consisting of halogen, CF 3 , CF 3 O, (C 1 -C 6 )alkyl, perfluoro(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )heteroalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )thioalkoxy, amino, (C 1 -C 6 )alkylamino, di(C 1 -C 6 )alkylamino, (C 3 -C 10 )cycloalkyl, (C 4 -C 10 )cycloalkyl-alkyl, (C 3 -C 10 )cycloheteroalkyl, cyano, nitro, sulfonamido, (C 1 -C 6 )acyl, (C 1 -C 6 )acylamino, (C 2 -C 6 )alkoxycarbonyl, (C 2 -C 6 )alkoxycarbonyl(C 1 -C 6 )alkyl, carboxamido and (C 1 -C 6 )heteroalkoxyl;

or pharmaceutically acceptable salts thereof.

38. A composition in accordance with claim 37 , wherein Y is selected from the group consisting of O and S.

39. A composition in accordance 37 , wherein Y is O.

40. A composition in accordance claim 37 , wherein Y is S.

41. A composition in accordance claim 37 , wherein Z is NR 2 R 3 .

42. A composition in accordance claim 38 , wherein R 4 is H.

43. A composition in accordance with claim 37 , wherein A is selected from the group consisting of:

wherein

R 5 , R 6 , R 7 and R 8 are independently selected from the group consisting of H, halogen, CF 3 , (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )heteroalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )thioalkoxy, amino, (C 1 -C 6 )alkylamino, di(C 1 -C 6 )alkylamino, (C 3 -C 10 )cycloalkyl, (C 4 -C 10 )cycloalkyl-alkyl, (C 3 -C 10 )cycloheteroalkyl, (C 3 -C 10 )cycloheteroalkyl-alkyl, cyano, nitro, (C 1 -C 6 )acyl, (C 1 -C 6 )acylamino, (C 2 -C 6 )alkoxycarbonyl, (C 3 -C 6 )alkoxycarbonylalkyl, CONH 2 , CO—NH—(C 1 -C 6 )alkyl, CO—N[(C 1 -C 6 )alkyl] 2 , SO 2 NH 2 , SO 2 NH—(C 1 -C 6 )alkyl, SO 2 N—[(C 1 -C 6 )alkyl] 2 and (C 1 -C 6 )heteroalkoxy; or two adjacent R groups can be linked together to form a new 5- or 6-membered carbocyclic or heterocyclic ring.

44. A composition in accordance with claim 37 , wherein Y is O or S; and A is selected from the group consisting of:

45. A composition in accordance with claim 37 , wherein B contains a nitrogen atom at a position two atoms away from the atom attaching B to the remainder of the molecule.

46. A composition in accordance with claim 37 , wherein B contains a nitrogen atom at the point of attachment of B to the remainder of the molecule.

47. A composition in accordance with claim 37 , wherein B is selected from the group consisting of 1-methylimidazol-5-yl, 1-(trifluoromethyl)imidazol-5-yl, 5-methylimidazol-1-yl, 5-(trifluoromethyl)imidazol-1-yl, thiazol-5-yl, imidazol-1-yl, 1-methyl-1,3,4-triazolyl, and 4-methyl-1,2,4-triazol-3-yl.

48. A composition in accordance with claim 37 , wherein B is selected from the group consisting of substituted or unsubstituted imidazolyl, substituted or unsubstituted thiazolyl and substituted or unsubstituted triazolyl.

49. A composition in accordance with claim 44 , wherein B contains a nitrogen atom at a position two atoms away from the atom attaching B to the remainder of the molecule.

50. A composition in accordance with claim 44 , wherein B contains a nitrogen atom at the point of attachment of B to the remainder of the molecule.

51. A composition in accordance with claim 44 , wherein B is selected from the group consisting of 1-methylimidazol-5-yl, 1-(trifluoromethyl)imidazol-5-yl, 5-methylimidazol-1-yl, 5-(trifluoromethyl)imidazol-1-yl, thiazol-5-yl, imidazol-1-yl, 1-methyl-1,3,4-triazolyl, and 4-methyl-1,2,4-triazol-3-yl.

52. A composition in accordance with claim 44 , wherein B is selected from the group consisting of substituted or unsubstituted imidazolyl, substituted or unsubstituted thiazolyl and substituted or unsubstituted triazolyl.

53. A method for treating rheumatoid arthritis said method comprising administering to a subject in need of such treatment, an effective amount of a compound having the formula:

wherein

W is N;

X is CH;

Y is selected from the group consisting of O, S and N(R);

 wherein R is selected from the group consisting of H, CN, NO 2 , (C 1 -C 10 )alkyl, (C 3 -C 10 )cycloalkyl, (C 4 -C 10 )cycloalkyl-alkyl, (C 3 -C 10 )alkenyl and (C 2 -C 10 )alkynyl;

Z is selected from the group consisting of H, (C 1 -C 10 )alkyl, (C 3 -C 10 )cycloalkyl, (C 4 -C 10 )cycloalkyl-alkyl, (C 2 -C 10 )alkenyl, (C 2 -C 10 )alkynyl and NR 2 R 3 ;

R 1 , R 2 and R 3 are independently selected from the group consisting of H, (C 1 -C 10 )alkyl, (C 3 -C 10 )alkenyl, (C 2 -C 10 )alkynyl, (C 2 -C 10 )heteroalkyl, (C 3 -C 10 )cycloalkyl, (C 4 -C 10 )cycloalkyl-alkyl, (C 3 -C 10 )cycloheteroalkyl-alkyl, (C 3 -C 10 )cycloheteroalkyl, aryl, aryl(C 1 -C 4 )alkyl, aryl(C 2 -C 4 )heteroalkyl, heteroaryl(C 2 -C 4 )alkyl, heteroaryl(C 2 -C 4 )heteroalkyl and perfluoro(C 1 -C 6 )alkyl; and wherein when Z is NR 2 R 3 , R 2 and R 3 can be combined to form a 5- to 7-membered ring; and wherein when Y is N(R), R and R 1 are optionally combined to form a 5- to 7-membered ring;

R 4 is selected from the group consisting of H, (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 4 -C 7 )cycloalkyl-alkyl, (C 2 -C 6 )alkenyl and (C 2 -C 6 )alkynyl;

A is a substituted or unsubstituted 6-membered fused carbocyclic or heterocyclic aromatic ring system, wherein the heterocyclic aromatic ring system contains 1-2 N atoms; and

B is a substituted or unsubstituted five- or six-membered ring which is aromatic, containing at least one nitrogen atom, and from 0 to 3 additional heteroatoms, wherein the B ring substituents are selected from the group consisting of halogen, CF 3 , CF 3 O, (C 1 -C 6 )alkyl, perfluoro(C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )heteroalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )thioalkoxy, amino, (C 1 -C 6 )alkylamino, di(C 1 -C 6 )alkyl amino, (C 3 -C 10 )cycloalkyl, (C 4 -C 10 )cycloalkyl-alkyl, (C 3 -C 10 )cycloheteroalkyl, cyano, nitro, sulfonamido, (C 1 -C 6 )acyl, (C 1 -C 6 )acylamino, (C 2 -C 6 )alkoxycarbonyl, (C 2 -C 6 )alkoxycarbonyl(C 1 -C 6 )alkyl, carboxamido and (C 1 -C 6 )heteroalkoxy;

or pharmaceutically acceptable salts thereof.

54. A method in accordance with claim 53 wherein Y is selected from the group consisting of O and S.

55. A method in accordance with claim 53 , wherein Y is O.

56. A method in accordance with claim 53 wherein Y is S.

57. A method in accordance with claim 53 wherein Z is NR 2 R 3 .

58. A method in accordance with claim 54 , wherein R 4 is H.

59. A method in accordance with claim 53 , wherein A is selected from the group consisting of:

wherein

R 5 , R 6 , R 7 and R 8 are independently selected from the group consisting of H, halogen, CF 3 , (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )heteroalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )thioalkoxy, amino, (C 1 -C 6 )alkylamino, di(C 1 -C 6 )alkylamino, (C 3 -C 10 )cycloalkyl, (C 4 -C 10 )cycloalkyl-alkyl, (C 3 -C 10 )cycloheteroalkyl, (C 3 -C 10 )cycloheteroalkyl-alkyl, cyano, nitro, (C 1 -C 6 )acyl, (C 1 -C 6 )acylamino, (C 2 -C 6 )alkoxycarbonyl, (C 3 -C 6 )alkoxycarbonylalkyl, CONH 2 , CO—NH—(C 1 -C 6 )alkyl, CO—N[(C 1 -C 6 )alkyl] 2 , SO 2 NH 2 , SO 2 NH—(C 1 -C 6 )alkyl, SO 2 N—[(C 1 -C 6 )alkyl] 2 and (C 1 -C 6 )heteroalkoxy; or two adjacent R groups can be linked together to form a new 5- or 6-membered carbocyclic or heterocyclic ring.

60. A method in accordance with claim 53 , wherein Y is O or S; and A is selected from the group consisting of:

61. A method in accordance with claim 53 , wherein B contains a nitrogen atom at a position two atoms away from the atom attaching B to the remainder of the molecule.

62. A method in accordance with claim 53 , wherein B contains a nitrogen atom at the point of attachment of B to the remainder of the molecule.

63. A method in accordance with claim 53 , wherein B is selected from the group consisting of 1-methylimidazol-5-yl, 1-(trifluoromethyl)imidazol-5-yl, 5-methylimidazol-1-yl, 5-(trifluoromethyl)imidazol-1-yl, thiazol-5-yl, imidazol-1-yl, 1-methyl-1,3,4-triazolyl, and 4-methyl-1,2,4-triazol-3-yl.

64. A method in accordance with claim 53 , wherein B is selected from the group consisting of substituted or unsubstituted imidazolyl, substituted or unsubstituted thiazolyl and substituted or unsubstituted triazolyl.

65. A method in accordance with claim 60 , wherein B contains a nitrogen atom at a position two atoms away from the atom attaching B to the remainder of the molecule.

66. A method in accordance with claim 60 , wherein B contains a nitrogen atom at the point of attachment of B to the remainder of the molecule.

67. A method in accordance with claim 60 wherein B is selected from the group consisting of 1-methylimidazol-5-yl, 1-(trifluoromethyl)imidazol-5-yl, 5-methylimidazol-1-yl, 5-(trifluoromethyl)imidazol-1-yl, thiazol-5-yl, imidazol-1-yl, 1-methyl-1,3,4-triazolyl, and 4-methyl-1,2,4-triazol-3-yl.

68. A method in accordance with claim 60 , wherein B is selected from the group consisting of substituted or unsubstituted imidazolyl, substituted or unsubstituted thiazolyl and substituted or unsubstituted triazolyl.

69. A method in accordance with claim 53 , wherein said compound is administered orally.

70. A method in accordance with claim 53 , wherein said compound is administered topically.

71. A method in accordance with claim 53 , wherein said compound is administered intravenously or intramuscularly.

72. A method in accordance with claim 53 , wherein said compound is administered in combination with a second therapeutic agent, said second therapeutic agent being a member selected from the group consisting of prednisone, dexamethasone, beclomethasone, methylprednisone, betamethasone, hydrocortisone, methotrexate, cyclosporin, rapamycin, tacrolimus, antihistamine drugs, TNF antibodies, IL-1 antibodies, soluble TNF receptors, soluble IL-1 receptors, TNF or IL-1 receptor antagonists, non-steroidal antiinflammatory agents, COX-2 inhibitors.

73. A method in accordance with claim 72 , wherein said administering is seqential.

Assignments (8)