ISOXAZOLE COMPOUNDS AS INHIBITORS OF HEAT SHOCK PROTEINS

摘要

Isoxazoles of formula (A) or (B) are inhibitors of HSP90 activity, and useful for treatment of, for example cancers: (A), (B) wherein R1, is a group of formula (IA): —Ar1-(Alk1)p-(Z)r-(Alk2)s-Q, wherein in any compatible combination Ar1 is an optionally substituted aryl or heteroaryl radical, Alk1 and Alk2 are optionally substituted divalent C1-C6 alkylene or C2-C6 alkenylene radicals, p, r and s are independently 0 or 1, Z is —O—, —S—, —(C═O)—, —(C═S)—, —SO2—, —C(═O)O—, —C(═O)NRA—, —C(═S)NRA—, —SO2NRA—, —NRAC(═O)—, —NRASO2— or —NRA— wherein RA is hydrogen or C1-C6 alkyl, and Q is hydrogen or an optionally substituted carbocyclic or heterocyclic radical; R2 is (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 -(Alk1)p-(Z)r-(Alk2)s-Q wherein Q, Alk1, Alk2, Z, p, r and s are as defined above in relation to group (IA); and R3 is hydrogen, optionally substituted cycloalkyl, cycloalkenyl, C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkynyl; or a carboxyl, carboxamide, or carboxyl ester group.