N-Aryl-benzimidazolones as novel small molecule HSP90 inhibitors

被引：38

作者：

Bruncko, Milan ^{[1
]}

Tahir, Stephen K. ^{[1
]}

Song, Xiaohong ^{[1
]}

Chen, Jun ^{[1
]}

Ding, Hong ^{[1
]}

Huth, Jeffrey R. ^{[2
]}

Jin, Sha ^{[1
]}

Judge, Russell A. ^{[2
]}

Madar, David J. ^{[1
]}

Park, Chang H. ^{[2
]}

Park, Cheol-Min ^{[1
]}

Petros, Andrew M. ^{[2
]}

Tse, Christin ^{[1
]}

Rosenberg, Saul H. ^{[1
]}

Elmore, Steven W. ^{[1
]}

机构：

[1] Abbott Labs, Global Pharmaceut R&D, Canc Res, Abbott Pk, IL 60064 USA

[2] Abbott Labs, Global Pharmaceut R&D, Struct Biol, Abbott Pk, IL 60064 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 24期

关键词：

HSP90; Benzimidazolone; Cancer; IMPORTANT BIOLOGIC ACTIVITIES; SHOCK-PROTEIN; 90; GELDANAMYCIN; CANCER; CHAPERONE; HEAT-SHOCK-PROTEIN-90; DOMAIN; ACTIVATION; RADICICOL; DISCOVERY;

D O I：

10.1016/j.bmcl.2010.10.010

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We describe the development of a novel series of N-aryl-benzimidazolone HSP90 inhibitors ( 9) targeting the N-terminal ATP-ase site. SAR development was influenced by structure-based design based around Xray structures of ligand bound HSP90 complexes. Lead compounds exhibited high binding affinities, ATPase inhibition and cellular client protein degradation. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：7503 / 7506

页数：4

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