Isoxazole compounds as inhibitors of heat shock proteins

Abstract

Isoxazoles of formula (A) or (B) are inhibitors of HSP90 activity, and useful for treatment of, for example cancers: (A), (B) wherein R, is a group of formula (IA): —Ar-(Alk)p-(Z)-(Alk)-Q, wherein in any compatible combination Aris an optionally substituted aryl or heteroaryl radical, Alkand Alkare optionally substituted divalent C-Calkylene or C-Calkenylene radicals, p, r and s are independently 0 or 1, Z is —O—, —S—, —(C═O)—, —(C═S)—, —SO—, —C(═O)O—, —C(═O)NR—, —C(═S)NR—, —SONR—, —NRC(═O)—, —NRSO— or —NR— wherein Ris hydrogen or C-Calkyl, and Q is hydrogen or an optionally substituted carbocyclic or heterocyclic radical; Ris (i) a group of formula (IA) above or (ii) a carboxamide radical; or (iii) a non aromatic carbocyclic or heterocyclic ring wherein a ring carbon is optionally substituted, and/or a ring nitrogen is optionally substituted by a group of formula -(Alk)p-(Z)-(Alk)-Q wherein Q, Alk, Alk, Z, p, r and s are as defined above in relation to group (IA); and Ris hydrogen, optionally substituted cycloalkyl, cycloalkenyl, C-Calkyl, C-Calkenyl, or C-Calkynyl; or a carboxyl, carboxamide, or carboxyl ester group.