Benzimidazole and imidazole inhibitors of histone deacetylases: Synthesis and biological activity

被引：46

作者：

Bressi, Jerome C. ^{[1
]}

de Jong, Ron ^{[1
]}

Wu, Yiqin ^{[1
]}

Jennings, Andy J. ^{[1
]}

Brown, Jason W. ^{[1
]}

O'Connell, Shawn ^{[1
]}

Tari, Leslie W. ^{[1
]}

Skene, Robert J. ^{[1
]}

Vu, Phong ^{[1
]}

Navre, Marc ^{[1
]}

Cao, Xiaodong ^{[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;

D O I：

10.1016/j.bmcl.2010.03.092

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of N-hydroxy-3-[3-(1-substituted-1H-benzoimidazol-2-yl)-phenyl]-acrylamides (5a-5ab) and N-hydroxy-3-[ 3-( 1,4,5-trisubstituted-1H-imidazol-2-yl)-phenyl]-acrylamides (12a-s) were designed, synthesized, and found to be nanomolar inhibitors of human histone deacetylases. Multiple compounds bearing an N1-piperidine demonstrate EC(50)s of 20-100 nM in human A549, HL60, and PC3 cells, in vitro and in vivo hyperacetylation of histones H3 and H4, and induction of p21(waf). Compound 5x displays efficacy in human tumor xenograft models. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：3138 / 3141

页数：4

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