3-(5-Chloro-2, 4-dihydroxyphenyl)-pyrazole-4-carboxamides as inhibitors of the Hsp90 molecular chaperone

…, K Grant, A Massey, A Surgenor, P Workman

Index: Brough, Paul A.; Barril, Xavier; Beswick, Mandy; Dymock, Brian W.; Drysdale, Martin J.; Wright, Lisa; Grant, Kate; Massey, Andrew; Surgenor, Allan; Workman, Paul Bioorganic and Medicinal Chemistry Letters, 2005 , vol. 15, # 23 p. 5197 - 5201

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Citation Number: 79

Abstract

Information from X-ray crystal structures of Hsp90 inhibitors bound to the human Hsp90 molecular chaperone was used to assist in the design of 3-(5-chloro-2, 4-dihydroxyphenyl)- pyrazole-4-carboxamides as novel inhibitors of Hsp90. Accessing an extra interaction with the protein via Phe138 gave a significant increase in binding potency compared to similar analogues that do not make this interaction.