New 4-substituted 3,5-dialkyl-isoxazole derivatives, useful as antiviral agents having strong activity against hepatitis B virus and low cytotoxicity

摘要

N-(Hetero)aryl-3,5-dialkylisoxazole-4-carboxamide derivatives (I) (including 4-thioamide, urea, thiourea or methylamine analogs) are new. Isoxazole derivatives of formula (I) are new. R1, R2 = alkyl (optionally substituted by one or more halo); X = -C(Y)-, -N(R4)-C(Y)-, CH2 or (CH2)nC(Y); n = 1-4; R3, R4 = H or optionally halo-substituted alkyl; Y = O or S; A = aryl or 6-membered heteroaryl (both optionally substituted by 1-3 of halo, alkyl, alkoxy, alkylthio, alkoxycarbonyl, NHCONH2, mono- or dialkylamino, CN, NH2 or mono- or dialkylamino, provided that substituents in the ortho-position are halo, alkyl, alkoxy or alkylthio). Independent claims are included for: (i) the preparation of (I); and (ii) combinations of (A) at least one isoxazole (not restricted to (I)), (B) at least one other anti-hepatitis B virus (HBV) agent and optionally (C) at least one immunomodulator.