| Literature DB >> 27234148 |
Peng Li1, Bailing Yang2, Fei Hao2, Ping Wang2, Haiying He3, Lei Huang2, Xuan Zhang2, Shengbin Zhang2, Xuanjia Peng2, Ke Yin2, Jiao Hu2, Xinsheng Chen2, Zhengxian Gu2, Li Wang2, Liang Shen2, Guoping Hu2, Ning Li2, Jian Li2, Shuhui Chen2, Wei Xiao4, Zhenzhong Wang4, Qingming Guo4, Xiujuan Chang4, Lanjun Zhang5, Qixu Cai5, Tianwei Lin5.
Abstract
Enterovirus 71 (EV71) is a major causative agent of hand, foot and mouth disease (HFMD), which can spread its infections to the central nervous and other systems with severe consequences. In this article, design, chemical synthesis, and biological evaluation of various anti-EV71 agents which incorporate Michael acceptors are described. Further SAR study demonstrated that lactone type of Michael acceptor provided a new lead of anti-EV71 drug candidates with high anti-EV71 activity in cell-based assay and enhanced mouse plasma stability. One of the most potent compounds (2K, cell-based anti-EV71 EC50=0.028μM), showed acceptable stability profile towards mouse plasma, which resulted into promising pharmacokinetics in mouse via IP administration.Entities:
Keywords: 3C protease inhibitor; Enterovirus 71; Michael acceptor
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Year: 2016 PMID： 27234148 DOI： 10.1016/j.bmcl.2016.05.036
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823