Small-molecule HSP90 inhibitors

US9701678B2 · kind B2 · utility

Assignee

• Memorial Sloan Kettering Cancer Center · US

Inventors

• Gabriela Chiosis · New York, US
• Huazhong He · Foshan, CN
• Laura Llauger-Bufi · Madrid, ES
• Joungnam Kim · Elmont, US
• Steve M. Larson · New York, US
• Peter Smith-Jones · Basel, CH

Key dates

• Filing date: Apr 18, 2014
• Grant date: Jul 11, 2017
• Expiry date: Apr 18, 2034

Classification

• Technology area (CPC G): Physics
• CPC primary: G01N33/60
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Hsp90 inhibitors having are provided having the formula: (I) with a 2′,4′,5′-substitution pattern on the right-side aryl moiety. X1 represents two substituents, which may be the same or different, disposed in the 4′ and 5′ positions on the aryl group, wherein X1 is selected from halogen, alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, pyrollyl, optionally substituted aryloxy, alkylamino, dialkylamino, carbamyl, amido, alkylamido dialkylamido, acylamino, alkylsulfonylamido, trihalomethoxy, trihalocarbon, thioalkyl, SO2-alkyl, COO-alkyl, KH2, OH, CN, SO2X5, NO2, NO, C═SR2NSO2X5, C═OR2, where X5 is F, NH2, alkyl or H, and R2 is alkyl, NH2, NH-alkyl or O-alkyl, C1 to C6 alkyl or alkoxy; or wherein X1 has the formula —O—(CH2)n—O—, wherein n is an integer from 0 to 2, preferably 1 or 2, and one of the oxygens 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.