3-(5-chloro-2,4-dihydroxyphenyl)-Pyrazole-4-carboxamides as inhibitors of the Hsp90 molecular chaperone
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- 作者：Paul A. Brough ; Xavier Barril ; Mandy Beswick ; Brian W. Dymock ; Martin J. Drysdale ; Lisa Wright ; Kate Grant ; Andrew Massey ; Allan Surgenor and Paul Workman
- 关键词：Hsp90 ; Cancer ; Structure-based drug design ; Pyrazole ; X-ray crystallography
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2005
- 出版时间：2005
- 年：2005
- 卷：15
- 期：23
- 页码：5197-5201
- 全文大小：234 K
文摘
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.