Title | 3-(5-Chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides as inhibitors of the Hsp90 molecular chaperone |
Publication Type | Journal Article |
Year of Publication | 2005 |
Authors | Brough, PA, Barril X, Beswick M, Dymock BW, Drysdale MJ, Wright L, Grant K, Massey A, Surgenor A, Workman P |
Journal | Bioorganic & medicinal chemistry letters |
Volume | 15 |
Issue | 23 |
Pagination | 5197 - 5201 |
Date Published | 2005/12/01/ |
Keywords | Amides/chemistry/pharmacology; Crystallography, X-Ray; Drug Design; HSP90 Heat-Shock Proteins/antagonists & inhibitors; Humans; Molecular Structure; Oxamic Acid/chemistry; Pyrazoles/chemistry/pharmacology |
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. |