Design and campaign synthesis of piperidine- and thiazole-based histone deacetylase inhibitors

被引：13

作者：

Andrews, David M. ^{[1
]}

Stokes, Elaine S. E. ^{[1
]}

Carr, Greg R. ^{[1
]}

Matusiak, Zbigniew S. ^{[1
]}

Roberts, Craig A. ^{[1
]}

Waring, Michael J. ^{[1
]}

Brady, Madeleine C. ^{[1
]}

Chresta, Christine M. ^{[1
]}

East, Simon J. ^{[1
]}

机构：

[1] AstraZeneca, Macclesfield SK10 4TG, Cheshire, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 08期

关键词：

HDAC; histone; deacetylase; anticancer; benzamide;

D O I：

10.1016/j.bmcl.2008.03.041

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A lead benzamide, 3, was identified as a potent and low molecular weight histone deacetylase ( HDAC) inhibitor. Optimization led to 16d, demonstrating an excellent balance of efficacy and non-efficacy properties, along with very desirable in vivo DMPK. The final compounds presented are > 1000-fold more potent than the initial screen hit, an improvement in potency which was achieved with a concomitant significant improvement in all the main non-efficacy properties. (c) 2008 Elsevier Ltd. All rights reserved.

引用

页码：2580 / 2584

页数：5

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