New N-substituted imidazole or triazole derivatives, useful as antifungal medicaments, e.g. for treating Candida, Aspergillus or Cryptococcus infections

摘要

Imidazole or triazole derivatives (I) and (II), N-substituted by an aralkylamino-terminated side-chain, are new. Imidazole or triazole derivatives of formula (I) and (II) (including all possible stereoisomers and stereoisomer mixtures) and their salts and prodrugs are new. X = N or CH; Ar1 = carbocyclic or heterocyclic aryl (optionally substituted (os) by one or more of R2, R3 and R4); Ar2 = phenylene or naphthylene (both os by one or more of R5, R6 and R7); Ar3 = carbocyclic or heterocyclic aryl (os by one or more of R8, R9 and R10); A1 = 1-4C alkylene; A2 = -CH=CH-A1- or -cyclopropylene-A1- (where the CH=CH or cyclopropylene moiety is os by R2 and/or R3); R1 = H, SO3H, alkyl (os by R2) or alkylene bonded to Ar1; R2 - R10 = F, Cl, Br, CN, 1-8C mono-, di- or trihaloalkyl, 1-8C mono-, di- or trihaloalkoxy, OH, NO2, COOH, CHO, SO3H, OSO3H, -P(O)(OR11)2, -O-P(O)(OR11)2, NH2, mono- or di-(1-8C alkyl)-amino, aralkylamino, arylamino, alkyl, aryl, heterocyclyl (os by =O), aralkyl, aminoalkyl, mono- or di-(1-8C alkyl)-aminoalkyl, hydroxyalkyl, alkoxyalkyl, 1-8C alkoxy (optionally interrupted by one or more O), aralkoxy, aryloxy, hydroxyalkoxy, alkoxyalkoxy, aminoalkoxy, alkylaminoalkoxy, di-(1-8C alkyl)-aminoalkoxy, OCH2O, alkoxycarbonyl, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkanoylamino, alkylsulfonylamino, arylsulfonylamino, aralkylsulfonylamino, alkylaminosulfonyl, aralkylaminosulfonyl, alkylsulfonyl or aralkylsulfonyl (where alkyl, aryl and heterocyclyl moieties are os by one or more of the groups cited above); R11 = H, 1-10C alkyl, 6-14C aryl or (6-14C) aryl-alkyl; unless specified otherwise alkyl moieties have 1-6C and aryl moieties 5-14C. Independent claims are included for: (i) the preparation of (I) or (II); and (ii) the use of chemical entities having a substituted phenoxy group of formula (a) at one terminal and a pharmacophore group having fungicidal activity (e.g. an imidazole or triazole group as in (I) or (II)) for the production of medicaments having antifungal medicaments. Q = (E)-vinylene or 1,2-cyclopropylene.