Pyrimidine compounds

1. A method for treating an interleukin-12 overproduction-related disorder selected from rheumatoid arthritis, sepsis, Crohn's disease, multiple sclerosis, psoriasis, or insulin-dependent diabetes mellitus, comprising administering to a subject in need thereof an effective amount of 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, or heteroaryl; and each of R c and R d , independently, is H, alkyl, aryl, heteroaryl, cyclyl, heterocyclyl, or alkylcarbonyl; or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein R 1 is

3. The method of claim 2 , wherein U is N and V is CH.

4. The method of claim 2 , wherein Z is N and W is O.

5. The method of claim 2 , wherein X is NR c .

6. The method of claim 5 , wherein R c is H, methyl, ethyl, or acetyl.

7. The method of claim 2 , wherein Y is O or CH 2 , and n is 0, 1, 2, 3, or 4.

8. The method of claim 7 , wherein R 3 is aryl or heteroaryl.

9. The method of claim 8 , wherein R 3 is pyridinyl.

10. The method of claim 7 , wherein R 3 is OR c , SR c , C(O)OR c , or C(O)NR c R d .

11. The method of claim 7 , 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.

12. The method of claim 2 , 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.

13. The method of claim 12 , wherein one of R a and R b is

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

14. The method of claim 13 , 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.

15. The method of claim 14 , wherein R g is methyl or methoxy; R i is H; and q is 0.

16. The method of claim 14 , wherein U is N and V is CH.

17. The method of claim 16 , wherein Z is N and W is O.

18. The method of claim 17 , wherein X is NR c ; and R c is H, methyl, ethyl, or acetyl.

19. The method of claim 18 , wherein Y is O or CH 2 ; and n is 0, 1, 2, 3, or 4.

20. The method of claim 19 , wherein R 3 is aryl or heteroaryl.

21. The method of claim 20 , wherein R 3 is pyridinyl.

22. The method of claim 14 , wherein Y is O or CH 2 , and n is 0, 1, 2, 3, or 4.

23. The method of claim 22 , wherein R 3 is aryl or heteroaryl.

24. The method of claim 22 , wherein R 3 is pyridinyl.

25. The method of claim 1 , wherein R 1 is aryl or heteroaryl.

26. The method of claim 25 , 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.

27. The method of claim 26 , wherein X is NR c ; and R c is H, methyl, ethyl, or acetyl.

28. The method of claim 27 , wherein U is N and V is CH.

29. The method of claim 28 , wherein Z is N and W is O.

30. The method of claim 29 , wherein Y is O or CH 2 ; and n is 0, 1, 2, 3, or 4.

31. The method of claim 26 , wherein Y is O or CH 2 ; and n is 0, 1, 2, 3, or 4.

32. The method of claim 31 , wherein R 3 is aryl or heteroaryl.

33. The method of claim 32 , wherein R 3 is pyridinyl.

34. The method of claim 31 , wherein R 3 is OR c , SR c , C(O)OR c or C(O)NR c R d .

35. The method of claim 31 , 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.

36. The method of claim 31 , wherein R 1 is

37. The method of claim 36 , wherein R j is methyl, ethyl, propyl, or benzo; and r is 1 or 2.