Exploration of the HDAC2 foot pocket: Synthesis and SAR of substituted N-(2-aminophenyl)benzamides

被引：213

作者：

Bressi, Jerome C. ^{[1
]}

Jennings, Andy J. ^{[1
]}

Skene, Robert ^{[1
]}

Wu, Yiqin ^{[1
]}

Melkus, Robert ^{[1
]}

De Jong, Ron ^{[1
]}

O'Connell, Shawn ^{[1
]}

Grimshaw, Charles E. ^{[1
]}

Navre, Marc ^{[1
]}

Gangloff, Anthony R. ^{[1
]}

机构：

[1] Takeda San Diego, San Diego, CA 92121 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 10期

关键词：

Histone deacetylase inhibitors; HDAC; Oncology; HISTONE DEACETYLASE; HYDROXAMIC ACID; INTERNAL CAVITY; INHIBITORS; DESIGN;

D O I：

10.1016/j.bmcl.2010.03.091

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of N-(2-amino-5-substituted phenyl)benzamides (3-21) were designed, synthesized and evaluated for their inhibition of HDAC2 and their cytotoxicity in HCT116 cancer cells. Multiple compounds from this series demonstrated time-dependent binding kinetics that is rationalized using a co-complex crystal structure of HDAC2 and N-(4-aminobiphenyl-3-yl) benzamide (6). (C) 2010 Elsevier Ltd. All rights reserved.

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页码：3142 / 3145

页数：4

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