☆ 4.5 Article

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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2010)

期刊

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷 20, 期 10, 页码 3138-3141

出版社

PERGAMON-ELSEVIER SCIENCE LTD

DOI: 10.1016/j.bmcl.2010.03.092

关键词

Histone deacetylase inhibitors; HDAC; Oncology

类别

Chemistry, Medicinal Chemistry, Organic

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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.

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