Design, synthesis and bioevalution of novel benzamides derivatives as HDAC inhibitors

Yanyang Li; Yan Zhou; Pengyu Qian; Yongzhen Wang; Falong Jiang; Zhenglin Yao; Wenxiang Hu; Yanjin Zhao; Shuxin Li

doi:10.1016/j.bmcl.2012.10.114

Design, synthesis and bioevalution of novel benzamides derivatives as HDAC inhibitors

Bioorg Med Chem Lett. 2013 Jan 1;23(1):179-82. doi: 10.1016/j.bmcl.2012.10.114. Epub 2012 Nov 5.

Authors

Yanyang Li¹, Yan Zhou, Pengyu Qian, Yongzhen Wang, Falong Jiang, Zhenglin Yao, Wenxiang Hu, Yanjin Zhao, Shuxin Li

Affiliation

¹ The General Hospital of Chinese People's Liberation Army, Beijing 100853, China.

PMID: 23206867
DOI: 10.1016/j.bmcl.2012.10.114

Abstract

A series of novel benzamides derivatives was designed and synthesized as HDAC inhibitors. Exploration of the structure-activity relationships resulted in compounds that are potent in vitro. In addition, the best compound 1a exhibited an acceptable pharmacokinetic profile with bioavailability in rat of 81% and could be considered as a candidate compound for further development.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / pharmacokinetics
Antineoplastic Agents / toxicity
Benzamides / chemical synthesis*
Benzamides / chemistry*
Benzamides / pharmacokinetics
Benzamides / toxicity
Cell Line, Tumor
Drug Design*
Drug Evaluation, Preclinical
Drug Screening Assays, Antitumor
HCT116 Cells
Half-Life
Histone Deacetylase Inhibitors / chemical synthesis*
Histone Deacetylase Inhibitors / pharmacokinetics
Histone Deacetylase Inhibitors / toxicity
Histone Deacetylases / chemistry*
Histone Deacetylases / metabolism
Humans
MCF-7 Cells
Pyrimidines / chemical synthesis*
Pyrimidines / pharmacokinetics
Pyrimidines / toxicity
Rats
Structure-Activity Relationship

Substances

Antineoplastic Agents
Benzamides
Histone Deacetylase Inhibitors
Pyrimidines
Histone Deacetylases