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

详细信息    查看全文

• 作者：Peng Li^a ; ^c ; Bailing Yang^a ; Fei Hao^a ; Ping Wang^a ; Haiying He^a ; ^{he_haiying@wuxiapptec.com" class="auth_mail" title="E-mail the corresponding author} ; Lei Huang^a ; Xuan Zhang^a ; Shengbin Zhang^a ; Xuanjia Peng^a ; Ke Yin^a ; Jiao Hu^a ; Xinsheng Chen^a ; Zhengxian Gu^a ; Li Wang^a ; Liang Shen^a ; Guoping Hu^a ; Ning Li^a ; Jian Li^a ; Shuhui Chen^a ; Wei Xiao^b ; ; Zhenzhong Wang^b ; Qingming Guo^b ; Xiujuan Chang^b ; Lanjun Zhang^c ; Qixu Cai^c ; Tianwei Lin^c
• 关键词：Enterovirus 71 ; 3C protease inhibitor ; Michael acceptor
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：15 July 2016
• 年：2016
• 卷：26
• 期：14
• 页码：3346-3350
• 全文大小：1778 K

文摘

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 (rong class="boldFont">2Krong>, cell-based anti-EV71 EC₅₀ = 0.028 μM), showed acceptable stability profile towards mouse plasma, which resulted into promising pharmacokinetics in mouse via IP administration.