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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