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

Title3-(5-Chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides as inhibitors of the Hsp90 molecular chaperone
Publication TypeJournal Article
Year of Publication2005
AuthorsBrough, PA, Barril X, Beswick M, Dymock BW, Drysdale MJ, Wright L, Grant K, Massey A, Surgenor A, Workman P
JournalBioorganic & medicinal chemistry letters
Pagination5197 - 5201
Date Published2005/12/01/
KeywordsAmides/chemistry/pharmacology; Crystallography, X-Ray; Drug Design; HSP90 Heat-Shock Proteins/antagonists & inhibitors; Humans; Molecular Structure; Oxamic Acid/chemistry; Pyrazoles/chemistry/pharmacology
AbstractInformation 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.