Pyrimidine compounds
View Patent ↗This invention features pyrimidine compounds of formula (I): R 1 is in which one of R a and R b is H or alkyl, and the other is aryl or heteroaryl optionally substituted with R d and R e m ; 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 R c is H, alkyl, aryl, heteroaryl, cyclyl, heterocyclyl, or alkylcarbonyl; R d is halogen, CN, alkyl alkyloxy, alkylcarbonyl, alkyloxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, hydroxyalkyl, alkylamino, or alkylaminocarbonyl; R e is halogen, CN, hydroxyl, alkyl, aryl, heteroaryl, alkoxyl, aryloxyl, or heteroaryloxyl; and m is 0, 1, 2, 3, or 4. The pyrimidine compounds can be used to treat an IL-12 overproduction-related disorder (e.g., rheumatoid arthritis, sepsis, Crohn's disease, multiple sclerosis, psoriasis, or insulin-dependent diabetes mellitus).
1. A compound of formula (I):
wherein R 1 is
in which one of R a and R b is H or alkyl, and the other is aryl or heteroaryl optionally substituted with R d and R e m ;
each of R 2 and R 2 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, CH2, C(0), C═N—R c , C═N—OR c , C═N—SR c , 0, S, S(0), S(02), 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(O2), NR c , or NC(0)R c ;
in which R o is H, alkyl, aryl, heteroaryl, cyclyl, heterocyclyl, or alkylcarbonyl;
R d is halogen, CN, alkyl, alkyloxy, alkylcarbonyl, alkyloxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, hydroxyalkyl, alkylamino, or alkylaminocarbonyl;
Re is halogen, CN, hydroxyl, alkyl, aryl, heteroaryl, alkoxyl, aryloxyl, or heteroaryloxyl; and
m is 0, 1, 2, 3, or 4.
2. The compound of claim 1 , wherein one of R a and R b is H or alkyl; and the other is:
in which Rd, Re, and m are as defined in claim 1 .
3. The compound of claim 2 , wherein one of R a and R b is H; and the other is:
in which R d is as defined in claim 1 .
4. The compound of claim 1 , wherein X is NH.
5. The compound of claim 4 , wherein one of R a and R b is H or alkyl; and the other is:
in which R d , R e , and m are as defined in claim 1 .
6. The compound of claim 5 , wherein one of R a and R b is H; and the other is:
in which R d is as defined in claim 1 .
7. The compound of claim 1 , wherein n is 2 .
8. The compound of claim 1 , wherein R 3 is heteroaryl or heterocyclyl.
9. The compound of claim 1 , wherein Y is O.
10. The compound of claim 9 , wherein n is 2.
11. The compound of claim 10 , wherein R 3 is heteroaryl or heterocyclyl.
12. The compound of claim 1 , wherein U is N and Y is CH.
13. The compound of claim 12 , wherein Z is N and W is O.
14. The compound of claim 13 , wherein Y is O.
15. The compound of claim 14 , wherein n is 2.
16. The compound of claim 15 , wherein R 3 is heteroaryl or heterocyclyl.
17. The compound of claim 16 , wherein R 3 is pyridin-2-yl.
18. The compound of claim 17 , wherein X is NH.
19. The compound of claim 18 , wherein one of R a and R b is H or alkyl; and the other is:
in which R d , R e , and m are as defined in claim 1 .
20. The compound of claim 19 , wherein one of R a and R b is H; and the other is:
in which R d is as defined in claim 1 .
21. The compound of claim 20 , wherein Rd is halogen.
22. The compound of claim 20 , wherein Rd is CN, hydroxyalkyl, alkylamino, alkylaminocarbonyl alkyloxycarbonyl.
23. The compound of claim 20 , wherein Rd is alkyloxycarbonyl.
24. The compound of claim 16 , wherein R 3 is 1H-pyridin-2-one.
25. The compound of claim 24 , wherein X is NH.
26. The compound of claim 25 , wherein one of R a and R b is H or alkyl; and the other is:
in which R d , R e , and m are as defined in claim 1 .
27. The compound of claim 26 , wherein one of Ra and Rb is H; and the other is:
in which Rd is as defined in claim 1 .
28. The compound of claim 27 , wherein Rd is alkyl.
29. The compound of claim 27 , wherein Rd is halogen.
30. The compound of claim 27 , wherein Rd is methoxycarbonyl.