Pyrimidine compounds
View Patent ↗This invention features pyrimidine compounds of formula (I): each of R 2 and R 4 is H; R 3 is H, alkyl, aryl, heteroaryl, cyclyl, heterocyclyl, or alkylcarbonyl; R 5 is H or alkyl; n is 0, 1, 2, 3, 4, 5, or 6; X is NR c ; Y is 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 R c is H, alkyl, aryl, heteroaryl, cyclyl, heterocyclyl, or alkylcarbonyl.
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
each of R 2 and R 4 is H;
R 3 is H, alkyl, aryl, heteroaryl, cyclyl, heterocyclyl, or alkylcarbonyl;
R 5 is H or alkyl;
N is 0, 1, 2, 3, 4, 5, or 6;
X is NR c ;
Y is 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 R c is H, alkyl, aryl, heteroaryl, cyclyl, heterocyclyl, or alkylcarbonyl; or a pharmaceutcally acceptable salt thereof.
2. The method of claim 1 , wherein the compound is
3. A pharmaceutical composition comprising a compound of formula (I):
wherein
each of and R 2 is R 4 is H;
R 3 is H, alkyl, aryl, heteroaryl, cyclyl, heterocyclyl, or alkylcarbonyl;
R 5 is H or alkyl;
n is 0, 1, 2, 3, 4, 5, or 6;
X is NR c ;
Y is covalent bond, CH 2 , C(O), 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 R c is H, alkyl, aryl, heteroaryl, cyclyl, heterocyclyl, or alkylcarbonyl; or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.
4. The pharmaceutical composition of claim 3 , wherein one of R a and R b is H or alkyl; and the other is
in which R d is H, alkyl, or alkoxyl; R e is halogen, CN, hydroxyl, alkyl, aryl, heteroaryl, alkoxyl, aryloxyl, or heteroaryloxyl; and m is 0, 1, 2, 3, or 4.
5. The pharmaceutical composition of claim 4 , wherein one of R a and R b is H; and the other is 3-methylphenyl.
6. The pharmaceutical composition of claim 3 , wherein X is NH.
7. The pharmaceutical composition or claim 6 , wherein one of R a and R b is H or alkyl; and the other is
in which R d is H, alkyl, or alkoxyl; R e is halogen, CN, hydroxyl, alkyl, aryl, heteroaryl, alkoxyl, aryloxyl, or heteroaryloxyl; and m is 0, 1, 2, 3, or 4.
8. The pharmaceutical composition of claim 7 , wherein one of R a and R b is H; and the other is 3-methylphenyl.
9. The pharmaceutical composition of claim 3 , wherein Y is O.
10. The pharmaceutical composition of claim 9 , wherein X is NH.
11. The pharmaceutical composition of claim 10 , wherein one of R a and R b is H or alkyl; and the other is
in which R d is H, alkyl, or alkoxyl; R e is halogen, CN, hydroxyl, alkyl, aryl, heteroaryl, alkoxyl, aryloxyl, or heteroaryloxyl; and m is 0, 1, 2, 3, or 4.
12. The pharmaceutical composition of claim 11 , wherein one of R a and R b is H; and the other is 3-methylphenyl.
13. The pharmaceutical composition of claim 3 , wherein n is 2.
14. The pharmaceutical composition of claim 13 , wherein Y is O.
15. The pharmaceutical composition or claim 14 , wherein X is NH.
16. The pharmaceutical composition of claim 15 , wherein one of R a and R b is H or alkyl; and the other is
in which R d is H, alkyl, or alkoxyl; R e is halogen, CN, hydroxyl, alkyl, aryl, heteroaryl, alkoxyl, aryloxyl, or heteroaryloxyl; and m is 0, 1, 2, 3, or 4.
17. The pharmaceutical composition of claim 16 , wherein one of R a and R b is H; and other 3-methylphenyl.
18. The pharmaceutical composition of claim 3 , wherein U is N and V is CH.
19. The pharmaceutical composition of claim 18 , wherein Z is N and W is O.
20. The pharmaceutical composition of claim 19 , wherein R 3 is heteroaryl.
21. The pharmaceutical composition of claim 20 , wherein R 3 is 1-oxy-pyridin-2-yl.
22. The pharmaceutical composition of claim 21 , wherein n is 2.
23. The pharmaceutical composition of claim 22 , wherein Y is O.
24. The pharmaceutical composition of claim 23 , wherein X is NH.
25. The pharmaceutical composition of claim 24 , wherein one of R a and R b is H or alkyl; and the other is
in which R d is H, alkyl, or alkoxyl; R e is halogen, CN, hydroxyl, alkyl, aryl, heteroaryl, alkoxyl, aryloxyl, or heteroaryloxyl; and m is, 0, 1, 2, 3, or 4.
26. The pharmaceutical composition of claim 25 , wherein one of R a and R b is H; and the other is 3-methylphenyl.
27. The method of claim 1 , wherein the disorder is rheumatoid arthritis.
28. The method of claim 1 , wherein the disorder is Crohn's disease.
29. The method of claim 1 , wherein the disorder is multiple sclerosis.
30. The method of claim 1 , wherein the disorder is psoriasis.
31. The method of claim 1 , wherein the disorder is insulin-dependent diabetes mellitus.
32. The method of claim 1 , wherein the disorder is sepsis.