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

被引：74
作者：
Brough, PA
Barril, X
Beswick, M
Dymock, BW
Drysdale, MJ
Wright, L
Grant, K
Massey, A
Surgenor, A
Workman, P
机构：
[1] Vernalis Ltd, Cambridge CB1 6GB, England
[2] Canc Res UK, Ctr Canc Therapeut, Inst Canc Res, Sutton SM2 5NG, Surrey, England
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 23期
关键词：
Hsp90; cancer; structure-based drug design; pyrazole; X-ray crystallography;
D O I：
10.1016/j.bmcl.2005.08.091
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
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. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码：5197 / 5201
页数：5
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