Heterocyclic compounds
This invention features a compound of formula (I): R 1 is aryl or heteroaryl; each of R 2 and R 4 , independently, is H, halogen, CN, alkyl, OR a , or NR a R b ; R 3 is H, halogen, CN, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cyclyl, heterocyclyl, OR a , OC(O)R a , OC(O)NR a R b , NR a R b , NR a C(O)R b , NR a S(O)R b , NR a S(O) 2 R b , NR a C(O)NR b R c , NR a C(S)NR b R c , NR a C(NR b )NR c R d , NR a C(O)OR b , S(O)NR a R b , S(O) 2 NR a R b , S(O)R a , S(O) 2 R a , C(O)R a , C(O)OR a , or C(O)NR a R b ; R 5 is H or alkyl; n is 0, 1, 2, 3, 4, 5, or 6; A is O, S, S(O), S(O) 2 , or NR e ; B is N or CR f ; X is O, S, S(O), S(O) 2 , NR e , or C(O); Y is a covalent bond, C(O), C═NR a , O, S, S(O), S(O) 2 , or NR e ; Z is N or CH; each of U and V, independently, is N or CR; and W is O, S, or NR e ; in which each of R a , R b , R c , and R d , independently, is H, alkyl, aryl, heteroaryl, cyclyl, or heterocyclyl; R e is H, alkyl, aryl, acyl, or sufonyl; and R f is H, alkyl, aryl, acyl, sulfonyl, alkoxyl, amino, ester, amide, CN, or halogen. The compound is useful for treating an interleukin-12 overproduction-related disorder.
1. A compound of formula (I):
wherein
R 1 is aryl or heteroaryl;
each of R 2 and R 4 , independently, is H, halogen, CN, alkyl, OR a or NR a R b ;
R 3 is H, halogen, CN, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cyclyl, heterocyclyl, OR a , OC(O)R a , OC(O)NR a R b , NR a R b , NR a C(O)R b , NR a S(O)R b , NR a S(O) 2 R b , NR a C(O)NR b R c , NR a C(S)NR b R c , NR a C(NR b )NR c R d , NR a C(O)OR b , S(O)NR a R b , S(O) 2 NR a R b , S(O)R a , S(O) 2 R a , C(O)R a , C(O)OR a , or C(O)NR a R b ;
R 5 is H or alkyl;
n is 0, 1, 2, 3, 4, 5, or 6;
A is O, NR e ;
B is N;
X is O, S, S(O), S(O) 2 , NR e , or C(O);
Y is a covalent bond, C(O), C═NR a , O, S, S(O), S(O) 2 , or NR e ;
Z is N or CH;
each of U and V, independently, is N; and
W is O, S, or NR e ;
in which each of R a , R b , R c , and R d , independently, is H, alkyl, aryl, heteroaryl, cyclyl, or heterocyclyl; R e is H, alkyl, aryl, acyl, or sulfonyl; and R f is H, alkyl, aryl, acyl, sulfonyl, alkoxyl, amino, ester, amide, CN, or halogen; and
provided that if each of U and V is N, Y is a covalent bond, n is 0, then R 3 is H, CN, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cyclyl, OR a , OC(O)R a , OC(O)NR a R b , NR a R b , NR a C(O)R b , NR a S(O)R b , NR a S(O) 2 R b , NR a C(O)NR b R c , NR a C(S)NR b R c , NR a C(NR b )NR c R d , NR a C(O)OR b , S(O)NR a R b , S(O) 2 NR a R b , S(O)R a , S(O) 2 R a , C(O)R a , C(O)OR a , or C(O)NR a R b .
2. The compound of claim 1 , wherein Z is N.
3. The compound of claim 2 , wherein W is O.
4. The compound of claim 1 , wherein X is NR e .
5. The compound of claim 1 , wherein Z is N.
6. The compound of claim 5 , wherein W is O.
7. The compound of claim 5 , wherein X is NR e .
8. The compound of claim 7 , wherein W is O.
9. The compound of claim 7 , wherein R 3 is halogen, CN, alkyl, aryl, heteroaryl, OR a OC(O)R a , NR a NR b , NR a C(O)R b , C(O)OR a , or C(O)NR a R b .
10. The compound of claim 9 , wherein R 3 is aryl, hetereoaryl, aryloxyl, or heteroaryloxyl.
11. The compound of claim 10 , wherein R 3 is hetereoaryl.
12. The compound of claim 10 , wherein R 3 is pyridinyl, triazolyl, tetrazolyl, pyrimidinyl, thiazolyl, indolyl, or indolizinyl.
13. The compound of claim 10 , wherein the compound is a N-oxide.
14. The compound of claim 8 , wherein R 1 is aryl.
15. The compound of claim 14 , wherein Y is NR e .
16. The compound of claim 14 , wherein Y is O.
17. The compound of claim 14 , wherein R 1 is
in which R g is H, halogen, CN, alkyl, or alkoxyl; R h is halogen, CN, hydroxyl, amino, alkyl, aryl, heteroaryl, alkoxyl, aryloxyl, heteroaryloxyl, acyl, alkoxycarbonyl, alkylcarbonoxyl, mono- and dialkylaminocarbonyl, amidinyl, ureayl, guanadinyl, sulfonyl, or sulfonamidyl; and m is 0, 1, 2, 3, or 4.
18. The compound of claim 17 , wherein R 1 is
19. The compound of claim 17 , wherein R g is H, F, Cl, Br, I, CN, Me, Et, Pr, i-Pr, OMe, or OEt.
20. The compound of claim 1 , wherein the compound is
21. A method for treating an interleukin-12 overproduction-related disorder, selected from the group consisting of 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 a compound of formula (I):
wherein
R 1 is aryl or heteroaryl;
each of R 2 and R 4 , independently, is H, halogen, CN, alkyl, OR a or NR a R b ;
R 3 is H, halogen, CN, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cyclyl, heterocyclyl, OR a , OC(O)R a , OC(O)NR a R b , NR a R b , NR a C(O)R b , NR a S(O)R b , NR a S(O) 2 R b , NR a C(O)NR b R c , NR a C(S)NR b R c , NR a C(NR b )NR c R d , NR a C(O)OR b , S(O)NR a R b , S(O) 2 NR a R b , S(O)R a , S(O) 2 R a , C(O)R a , C(O)OR a , or C(O)NR a R b ;
R 5 is H or alkyl;
n is 0, 1, 2, 3, 4, 5, or 6;
A is O, NR e ;
B is N;
X is O, S, S(O), S(O) 2 , NR e , or C(O);
Y is a covalent bond, C(O), C═NR a , O, S, S(O), S(O) 2 , or NR e ;
Z is N or CH;
each of U and V, independently, is N; and
W is O, S, or NR e ;
in which each of R a , R b , R c , and R d , independently, is H, alkyl, aryl, heteroaryl, cyclyl, or heterocyclyl; R e is H, alkyl, aryl, acyl, or sulfonyl; and R f is H, alkyl, aryl, acyl, sulfonyl, alkoxyl, amino, ester, amide, CN, or halogen.
22. The method of claim 21 , wherein Z is N.
23. The method of claim 22 , wherein W is O.
24. The method of claim 21 , wherein X is NR e .
25. The method of claim 21 , wherein Z is N.
26. The method of claim 25 , wherein W is O.
27. The method of claim 21 , wherein X is NR e .
28. The method of claim 21 , wherein the compound is