2. Academic Validation
  3. Design, synthesis, and biological evaluation of anti-EV71 agents

Design, synthesis, and biological evaluation of anti-EV71 agents

  • Bioorg Med Chem Lett. 2016 Jul 15;26(14):3346-3350. doi: 10.1016/j.bmcl.2016.05.036.
Peng Li 1,  Bailing Yang 2,  Fei Hao 2,  Ping Wang 2,  Haiying He 3,  Lei Huang 2,  Xuan Zhang 2,  Shengbin Zhang 2,  Xuanjia Peng 2,  Ke Yin 2,  Jiao Hu 2,  Xinsheng Chen 2,  Zhengxian Gu 2,  Li Wang 2,  Liang Shen 2,  Guoping Hu 2,  Ning Li 2,  Jian Li 2,  Shuhui Chen 2,  Wei Xiao 4,  Zhenzhong Wang 4,  Qingming Guo 4,  Xiujuan Chang 4,  Lanjun Zhang 5,  Qixu Cai 5,  Tianwei Lin 5
Affiliations

Affiliations

  • 1 WuXi AppTec (Shanghai) Co., Ltd, 288 FuTe Zhong Road, Shanghai 200131, People's Republic of China; State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, People's Republic of China.
  • 2 WuXi AppTec (Shanghai) Co., Ltd, 288 FuTe Zhong Road, Shanghai 200131, People's Republic of China.
  • 3 WuXi AppTec (Shanghai) Co., Ltd, 288 FuTe Zhong Road, Shanghai 200131, People's Republic of China. Electronic address: he_haiying@wuxiapptec.com.
  • 4 Jiangsu Kanion Pharmaceutical Co., Ltd, 58 Haichangnan Road, Lianyungang 222001, People's Republic of China.
  • 5 State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, People's Republic of China.
PMID: 27234148 DOI: 10.1016/j.bmcl.2016.05.036
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.

Keywords

3C protease inhibitor; Enterovirus 71; Michael acceptor.

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