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http://dx.doi.org/10.5012/bkcs.2012.33.2.535

Synthesis and Biological Evaluation of N-(Aminopyridine) Benzamide Analogues as Histone Deacetylase Inhibitors  

Zhang, Qing-Wei (State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, China Pharmaceutical Industry Research Institute)
Li, Jian-Qi (State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, China Pharmaceutical Industry Research Institute)
Publication Information
Bulletin of the Korean Chemical Society / v.33, no.2, 2012 , pp. 535-540 More about this Journal
Abstract
A series of benzamide-based histone deacetylases (HDACs) inhibitors possessing N-(aminopyridine) residue as the zinc binding site of HDAC were synthesized and evaluated. Among these derivatives, compounds with N-(2-amino-4-pyridine) benzamide moiety have been found as the most potent ones. Moreover, introduction of appropriate substituents on the terminal aryl group acting as the surface-recognition domain could significantly improve the antiproliferative activity. In particular, the compound 4k possessed favorable pharmacokinetic characteristics and exhibited potent antitumor activity on xenograft model in mice at well tolerated doses, thus suggesting a good therapeutic index.
Keywords
N-(Aminopyridine) benzamide; HDAC inhibition; Anticancer activity;
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