Pyrimidine 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 and R 4 , independently, is R c , halogen, nitro, cyano, isothionitro, SR c , or OR c ; or R 2 and R 4 , taken together, is carbonyl;

R 3 is R c , alkenyl, alkynyl, OR c , OC(O)R c , SO 2 R c , S(O)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 ; R 5 is H or alkyl;

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

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;

one of U and V is N, and the other is CR C ; 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, aryl, heteroaryl, cyclyl, heterocyclyl, or alkylcarbonyl; or pharmaceutically acceptable salt thereof.

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

wherein

R 1 is

aryl, or heteroaryl;

each of R 2 and R 4 , independently, is R c , halogen, nitro, cyano, isothionitro, SR c , or OR c ; or R 2 and R 4 , taken together, is carbonyl;

R 3 is R c , alkenyl, alkynyl, OR c , OC(O)R c , SO 2 R c , S(O)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 ;

R 5 is H or alkyl;

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

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;

one of U and V is N, and the other is CR c ; 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, aryl, heteroaryl, cyclyl, heterocyclyl, or alkylcarbonyl; or pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

3. The pharmaceutical composition of claim 2 , wherein R 1 is

4. The pharmaceutical composition of claim 3 , wherein U is N and V is CH.

5. The pharmaceutical composition of claim 3 , wherein Z is N and W is O.

6. The pharmaceutical composition of claim 3 , wherein X is NR c .

7. The pharmaceutical composition of claim 6 , wherein R c is H, methyl, ethyl, or acetyl.

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

9. The pharmaceutical composition of claim 8 , wherein R 3 is aryl or heteroaryl.

10. The pharmaceutical composition of claim 9 , wherein R 3 is pyridinyl.

11. The pharmaceutical composition of claim 8 , wherein R 3 is OR c , SR c , C(O)OR c , or C(O)NR c R d .

12. The pharmaceutical composition of claim 8 , 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.

13. The pharmaceutical composition of claim 3 , 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, NO 2 , CN, alkyl, aryl, heteroaryl, OR c , OC(O)R c , SO 2 R c , S(O)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 ;

R i is H, alkyl, or alkylcarbonyl;

p is 0, 1, or 2; and

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

14. The pharmaceutical composition of claim 13 , wherein one of R a and R b is

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

15. The pharmaceutical composition of claim 14 , wherein R g is H, methyl, ethyl, propyl, cyclopropyl, methoxy, or ethoxy; R h is F, Cl, CN, methyl, methoxy, ethoxy, OC(O)CH 3 , OC(O)C 2 H 5 , C(O)OH, C(O)OC 2 H 5 , C(O)NH 2 , NHC(O)CH 3 , or S(O 2 )NH 2 ; R i is H, methyl, ethyl, or acetyl, and q is 0, 1, or 2.

16. The pharmaceutical composition of claim 15 , wherein R g is methyl or methoxy; R i is H; and q is 0.

17. The pharmaceutical composition of claim 15 , wherein U is N and V is CH.

18. The pharmaceutical composition of claim 17 , wherein Z is N and W is O.

19. The pharmaceutical composition of claim 18 , wherein X is NR c ; and R c is H, methyl, ethyl, or acetyl.

20. The pharmaceutical composition of claim 19 , wherein Y is O or CH 2 ; and n is 0, 1, 2, 3, or 4.

21. The pharmaceutical composition of claim 20 , wherein R 3 is aryl or heteroaryl.

22. The pharmaceutical composition of claim 21 , wherein R 3 is pyridinyl.

23. The pharmaceutical composition of claim 15 , wherein Y is O or CH 2 , and n is 0, 1, 2, 3, or 4.

24. The pharmaceutical composition of claim 23 , wherein R 3 is aryl or heteroaryl.

25. The pharmaceutical composition of claim 23 , wherein R 3 is pyridinyl.

26. The pharmaceutical composition of claim 2 , wherein R 1 is aryl or heteroaryl.

27. The pharmaceutical composition of claim 26 , wherein R 1 is

in which

D is O, S, or NR m ;

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

R m is H, alkyl, or alkylcarbonyl; and

r is 0, 1, or 2.

28. The pharmaceutical composition of claim 27 , wherein X is NR c ; and R c is H, methyl, ethyl, or acetyl.

29. The pharmaceutical composition of claim 28 , wherein U is N and V is CH.

30. The pharmaceutical composition of claim 29 , wherein Z is N and W is O.

31. The pharmaceutical composition of claim 30 , wherein Y is O or CH 2 ; and n is 0, 1, 2, 3, or 4.

32. The pharmaceutical composition of claim 27 , wherein Y is O or CH 2 ; and n is 0, 1, 2, 3, or 4.

33. The pharmaceutical composition of claim 32 , wherein R 3 is aryl or heteroaryl.

34. The pharmaceutical composition of claim 33 , wherein R 3 is pyridinyl.

35. The pharmaceutical composition of claim 32 , wherein R 3 is OR c , SR c , C(O)OR c or C(O)NR c R d .

36. The pharmaceutical composition of claim 32 , 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.

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

38. The pharmaceutical composition of claim 37 , wherein R j is methyl, ethyl, propyl, or benzo; and r is 1 or 2.

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

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

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

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

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

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

45. The method of claim 1 , wherein the compound of formula (I) is:

46. The pharmaceutical composition of claim 2 , wherein the compound of formula (I) is: