Small-molecule hsp90 inhibitors

Abstract

Hsp90 inhibitors are provided having the formula: with a 2',4′,5′-substitution pattern on the right-side aryl moiety. Xrepresents two substituents, which may be the same or different, disposed in the 4′ and 5′ positions on the aryl group, wherein Xis selected from halogen, alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, pyrollyl, optionally substituted aryloxy, alkylamino, dialkylamino, carbamyl, amido, alkylamido dialkylamido, acylamino, alkylsulfonylamido, trihalomethoxy, trihalocarbon, thioalkyl, SOalkyl, COO-alkyl, KH, OH, CN, SOX, NO, NO, C═SRNSOX, C═OR, where Xis F, NH2, alkyl or H, and Ris alkyl, NH, NH-alkyl or O-alkyl, Cto Calkyl or alkoxy; or wherein Xhas the formula —O—(CH)—O—, wherein n is an integer from 0 to 2, preferably 1 or 2, and one of the oxygen is bonded at the 5′-position and the other at the 4′-position of the aryl ring. The compounds are useful in cancer therapy and as radioimaging ligands.