Pyrimidine compounds and uses thereof

Details Pyrimidine compounds and uses thereof Pyrimidine compounds and uses thereof

A - Human Necessities

61

K

A61K 31/5377 (2006.01)

Patent

CA 2587590

This invention features pyrimidine compounds of formula (I): Rl is formula (A), aryl, or heteroaryl; each of R2 and R4, independently, is Rc, halogen, nitro, cyano, isothionitro, SRc, or ORc; or R2 and R4, taken together, is carbonyl; R3 is Rc, alkenyl, alkynyl, ORc, OC(O)Rc, SO2Rc, S(O2)NRc Rd, NRcCORd, NRcC(O)ORd, NRcC(O)NRcRd, NRcSO2Rd, CORc, C(O)ORc, or C(O)NRcRd; R5 is H or alkyl; n is 0, 1, 2, 3, 4, 5, or 6; X is O, S, S(O), S(O2), or NRc; Y is a covalent bond, CH2, C(O), C=N-Rc, C=N-ORc, C=N-SRc, O, S, S(O), S(O2), or NRc; Z is N or CH; one of U and V is N, and the other is CRc; and W is O, S, S(O), S(O2), NRc, or NC(O)Rc; in which each of Ra and Rb, independently, is H, alkyl, aryl, heteroaryl; and each of Rc and Rd, independently, is H, alkyl, aryl, heteroaryl, cyclyl, heterocyclyl, or alkylcarbonyl. The featured compounds inhibit the production of IL-12, IL-23 and IL-27 and are useful for treating disorders associated with IL- 12, IL-23 and IL-27 overproduction or misregulation, such as inflammatory and immune disorders.

La présente invention concerne des composés de pyrimidine de formule (I) dans laquelle: R1 est un composé de formule (A), aryle, ou hétéroaryle; R2 et R4 sont chacun indépendamment Rc, halogène, nitro, cyano, isothionitro, SRc, ou ORc; ou R2 et R4, forment ensemble carbonyle; R3 est Rc, alcényle, alcynyle, ORc, OC(O)Rc, SO2Rc, S(O)Rc, S(O2)NRc Rd, SRc, NRcRd, NRcCORd, NRcC(O)ORd, NRcC(O)NRcRd, NRcSO2Rd, CORc, C(O)ORc, ou C(O)NRcRd; R5 est H ou alkyle; n vaut 0, 1, 2, 3, 4, 5, ou 6; X est O, S, S(O), S(O2), ou NRc; Y est une liaison covalente, CH2, C(O), C=N-Rc, C=N-ORc, C=N-SRc, O, S, S(O), S(O2), ou NRc; Z est N ou CH; U ou V est N, alors que l'autre est CRc; et W est O, S, S(O), S(O2), NRc, ou NC(O)Rc; Ra et Rb étant indépendamment H, alkyle, aryle, hétéroaryle; et Rc et Rd étant chacun indépendamment H, alkyle, aryle, hétéroaryle, cyclyle, hétérocyclyle, ou alkylcarbonyle. Les composés de l'invention inhibent la production de IL-12, IL-23 et IL-27, et sont utiles pour traiter des troubles associés à la surproduction ou la mauvaise régulation de IL- 12, IL-23 et IL-27, tels que les troubles inflammatoires et les troubles immuns.

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