Triazine compounds

1. A method for treating an interleukin-12 overproduction-related disorder, wherein the disorder is rheumatoid arthritis, sepsis, Crohn's disease, multiple sclerosis, psoriasis, or insulin-dependent diabetes mellitus, comprising administering to a subject in need thereof the compound of formula (I):

wherein

R 1 is

 aryl, or heteroaryl;

each of R 2, R 4, and R 5, independently, is R c , halogen, nitro, nitroso, cyano, azide, isothionitro, SR c , or OR c ;

R 3 is R c , alkenyl, alkynyl, aryl, heteroaryl, cyclyl, heterocyclyl, OR c OC(O)R c , SO 2 R c , S(O 2 )R c , S(O 2 )NR c R d , SR c , NR c R d , NR c COR d , NR c C(O)OR d , NR c C(O)NR c R d , NR c SO 2 R d , COR c , C(O)OR c or C(O)NR c R d ;

n is 0, 1, 2, 3, 4, 5, 6, or 7;

X is O, S, S(O), S(O 2 ), or NR c ;

Y is a covalent bond, CH 2 , C(O), C═N—R c , C═N—OR c , C═N—SR c , O, S, S(O), S(O 2 ), or NR c .

Z is N or CH; and

W is O, S, S(O), S(O 2 ), NR c , or NC(O)R c ;

in which each of R a and R b , independently, is H, alkyl, aryl, heteroaryl; and each of R c and R d , independently, is H, alkyl, or alkylcarbonyl; or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein the disorder is rheumatoid arthritis.

3. The method of claim 1 , wherein the disorder is Crohn's disease.

4. The method of claim 1 , wherein the disorder is multiple sclerosis.

5. The method of claim 1 , wherein the disorder is psoriasis.

6. The method of claim 1 , wherein the disorder is diabetes mellitus.

7. The method of claim 1 , wherein the disorder is sepsis.

8. A pharmaceutical composition comprising the compound of formula (I):

wherein

R 1 is

 aryl, or heteroaryl;

each of R 2 , R 4 , and R 5 , independently, is R c , halogen, nitro, nitroso, cyano, azide, isothionitro, SR c , or OR c ;

R 3 is R c , alkenyl, alkynyl, aryl, heteroaryl, cyclyl, heterocyclyl, OR c , OC(O)R c , SO 2 R c , S(O 2 )R c , S(O 2 )NR c R d , SR c , NR c R d , NR c COR d , NR c C(O)OR d , NR c C(O)NR c R d , NR c SO 2 R d , COR c , C(O)OR c , or C(O)NR c R d ;

n is 0, 1, 2, 3, 4, 5, 6, or 7;

X is O, S, S(O), S(O 2 ), or NR c ,

Y is a covalent bond, CH 2 , C(O), C═N—R c , C═N—OR c , C═N—SR c , (O), S, S(O), S(O 2 ), or NR c ;

Z is N or CH; and

W is O, S, S(O), S(O 2 ), NR c , or NC(O)R c ;

in which each of R a and R b , independently, is H, alkyl, aryl, heteroaryl; and each of R c and R d , independently, is H, alkyl, or alkylcarbonyl; or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

9. The pharmaceutical composition of claim 8 , wherein R 1 is

10. The pharmaceutical composition of claim 9 , wherein W is O.

11. The pharmaceutical composition of claim 10 , wherein R 5 is H or alkyl.

12. The pharmaceutical composition of claim 9 , wherein X is NR c .

13. The pharmaceutical composition of claim 12 , wherein R c is H, methyl, ethyl, or acetyl.

14. The pharmaceutical composition of claim 9 , wherein Y is O or CH 2, and n is 0, 1, 2, 3, or 4.

15. The pharmaceutical composition of claim 14 , wherein R 3 is aryl or heteroaryl.

16. The pharmaceutical composition of claim 15 , wherein R 3 is pyridinyl.

17. The pharmaceutical composition of claim 14 , wherein R 3 is OR c , SR c , C(O)OR c , or C(O)NR c R d .

18. The pharmaceutical composition of claim 14 , wherein R 3 is

in which each of A and A′, independently, is O, S, or NH;

each of R e and R f , independently is H, alkyl, aryl, or heteroaryl; and

m is 1 or 2.

19. The pharmaceutical composition of claim 9 , wherein one of R a and R b is

in which

B is NR i , O, or S;

B′ is N or CR i ;

R g is H, alkyl, or alkoxyl;

R h is halogen, CN, hydroxyl, alkyl, aryl, heteroaryl, alkoxyl, aryloxyl, or heteroaryloxyl;

R i is H, alkyl, or alkylcarbonyl;

p is 0, 1, or 2; and

q is 0, 1,2, 3, or 4.

20. The pharmaceutical composition of claim 19 , wherein one of R a and R b is

and the other of R a and R b is alkyl.

21. The pharmaceutical composition of claim 20 , wherein R g is H, methyl, ethyl, methoxy, or ethoxy; R h is F, Cl, CN, methoxy, methyl, or ethoxy; R i is H, methyl, ethyl, or acetyl, and q is 0, 1, or 2.

22. The pharmaceutical composition of claim 21 , wherein R g is methyl or methoxy; R i is H; and q is 0.

23. The pharmaceutical composition of claim 21 , wherein W is O; and R 5 is H or alkyl.

24. The pharmaceutical composition of claim 23 , wherein X is NR c ; and R c is H, methyl, ethyl, or acetyl.

25. The pharmaceutical composition of claim 24 , wherein Y is O or CH 2 ; and n is 0, 1, 2, 3, or 4.

26. The pharmaceutical composition of claim 25 , wherein R 3 is aryl or heteroaryl.

27. The pharmaceutical composition of claim 26 , wherein R 3 is pyridinyl.

28. The pharmaceutical composition of claim 21 , wherein Y is O or CH 2, and n is 0, 1, 2, 3, or 4.

29. The pharmaceutical composition of claim 28 , wherein R 3 is aryl or heteroaryl.

30. The pharmaceutical composition of claim 29 , wherein R 3 is pyridinyl.

31. The pharmaceutical composition of claim 8 , wherein R 1 is aryl or heteroaryl.

32. The pharmaceutical composition of claim 30 , wherein R 1 is

in which D is O, S, or NR m ;

D′ is N or CR m ;

R j is halogen, CN, hydroxyl, alkyl, aryl, heteroaryl, alkoxyl, aryloxyl, or heteroaryloxyl;

R k is aryl or heteroaryl;

R l is H, alkyl, or alkylcarbonyl;

R m is H, alkyl, or alkylcarbonyl;

r is 0, 1, or 2;

s is 0 or 1;

t is 0, 1, 2, 3, or 4; and

u is 0, 1, 2, 3, 4, or 5.

33. The pharmaceutical composition of claim 32 , wherein X is NR c ; and R c is H, methyl, ethyl, or acetyl.

34. The pharmaceutical composition of claim 33 , wherein W is O; and R 5 is H or alkyl.

35. The pharmaceutical composition of claim 34 , wherein Y is O or CH 2; and n is 0, 1, 2, 3, or 4.

36. The pharmaceutical composition of claim 32 , wherein Y is O or CH 2; and n is 0, 1, 2, 3, or 4.

37. The pharmaceutical composition of claim 36 , wherein R 3 is aryl or heteroaryl.

38. The pharmaceutical composition of claim 37 , wherein R 3 is pyridinyl.

39. The pharmaceutical composition of claim 36 , wherein R 3 is OR c , SR c , C(O)OR c or C(O)NR c R d .

40. The pharmaceutical composition of claim 36 , wherein R 3 is

in which each of A and A′, independently, is O, S, or NH;

each of R e and R f , independently is H, alkyl, aryl, or heteroaryl; and

m is 1 or 2.

41. The pharmaceutical composition of claim 36 , wherein R 1 is

42. The pharmaceutical composition of claim 41 , wherein R j is methyl, ethyl, propyl, or benzyl; and r is 1 or 2.

43. The pharmaceutical composition comprising the compound of formula (I):

wherein R 1 is

 aryl, or heteroaryl;

each of R 2 , R 4 , and R 5 , independently, is R c , halogen, nitro, nitroso, cyano, azide, isothionitro, SR c , or OR c ;

R 3 is R c , alkenyl, alkynyl, aryl, heteroaryl, cyclyl, heterocyclyl, OR c , OC(O)R c , SO 2 R c , S(O 2 )R c , S(O 2 )NR c R d , SR c , NR c R d , NR c COR d , NR c C(O)OR d , NR c C(O)NR c R d , NR c SO 2 R d , COR c , C(O)OR c , or C(O)NR c R d ;

n is 0, 1, 2, 3, 4, 5, 6, or 7;

X is O, S, S(O), S(O 2 ), or NR c ;

Y is a covalent bond, CH 2 , C(O), C═N—R c , C═N—OR c , C═N—SR c , O, S, S(O), S(O 2 ), or NR c ;

Z is CH; and

W is O, S, S(O), S(O 2 ), NR c , or NC(O)R c ;

in which each of R a and R b , independently, is H, alkyl, aryl, heteroaryl; and each of R c and R d , independently, is H, alkyl, or alkylcarbonyl; or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

44. The pharmaceutical composition of claim 43 , wherein R 1 is

45. The pharmaceutical composition of claim 44 , wherein W is O; and R 5 is H or alkyl.

46. The pharmaceutical composition of claim 44 , wherein X is NR c ; and R c is H, methyl, ethyl, or acetyl.

47. The pharmaceutical composition of claim 44 , wherein Y is O or CH 2 , and n is 0, 1, 2, 3, or 4.

48. The pharmaceutical composition of claim 44 , wherein one of R a and R b is

in which B is NR i , O, or S;

B′ is N, CH, or CR i ;

R g is H, alkyl, or alkoxyl;

R h is halogen, CN, hydroxyl, alkyl, aryl, heteroaryl, alkoxyl, aryloxyl, or heteroaryloxyl;

R i is H, alkyl, or alkylcarbonyl;

p is 0, 1, or 2; and

q is 0, 1,2, 3, or 4.

49. The pharmaceutical composition of claim 43 , wherein R 1 is aryl or heteroaryl.

50. The pharmaceutical composition of claim 49 , wherein W is O; and R 5 is H or alkyl.

51. The pharmaceutical composition of claim 49 , wherein X is NR c ; and R c is H, methyl, ethyl, or acetyl.

52. The pharmaceutical composition of claim 49 , wherein Y is O or CH 2 ; and n is 0, 1, 2, 3, or 4.

53. The pharmaceutical composition of claim 49 , wherein R 1 is

in which D is O, S, or NR m ;

D′ is N or CR m ;

R j is halogen, CN, hydroxyl, alkyl, aryl, heteroaryl, alkoxyl, aryloxyl, or heteroaryloxyl;

R k is aryl or heteroaryl;

R l is H, alkyl, or alkylcarbonyl;

R m is H, alkyl, or alkylcarbonyl;

r is 0, 1, or 2;

s is 0 or 1;

t is 0, 1, 2, 3, or 4; and

u is 0, 1, 2, 3, 4, or 5.