title: Design, synthesis, and biological evaluation of anti-EV71 agents.
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.
authors.affiliation: 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.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: WuXi AppTec (Shanghai) Co., Ltd, 288 FuTe Zhong Road, Shanghai 200131, People's Republic of China.
authors.forename: Bailing
authors.initials: B
authors.lastname: Yang
authors.affiliation: WuXi AppTec (Shanghai) Co., Ltd, 288 FuTe Zhong Road, Shanghai 200131, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Hao
authors.affiliation: WuXi AppTec (Shanghai) Co., Ltd, 288 FuTe Zhong Road, Shanghai 200131, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: WuXi AppTec (Shanghai) Co., Ltd, 288 FuTe Zhong Road, Shanghai 200131, People's Republic of China. Electronic address: he_haiying@wuxiapptec.com.
authors.forename: Haiying
authors.initials: H
authors.lastname: He
authors.affiliation: WuXi AppTec (Shanghai) Co., Ltd, 288 FuTe Zhong Road, Shanghai 200131, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.affiliation: WuXi AppTec (Shanghai) Co., Ltd, 288 FuTe Zhong Road, Shanghai 200131, People's Republic of China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: WuXi AppTec (Shanghai) Co., Ltd, 288 FuTe Zhong Road, Shanghai 200131, People's Republic of China.
authors.forename: Shengbin
authors.initials: S
authors.lastname: Zhang
authors.affiliation: WuXi AppTec (Shanghai) Co., Ltd, 288 FuTe Zhong Road, Shanghai 200131, People's Republic of China.
authors.forename: Xuanjia
authors.initials: X
authors.lastname: Peng
authors.affiliation: WuXi AppTec (Shanghai) Co., Ltd, 288 FuTe Zhong Road, Shanghai 200131, People's Republic of China.
authors.forename: Ke
authors.initials: K
authors.lastname: Yin
authors.affiliation: WuXi AppTec (Shanghai) Co., Ltd, 288 FuTe Zhong Road, Shanghai 200131, People's Republic of China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Hu
authors.affiliation: WuXi AppTec (Shanghai) Co., Ltd, 288 FuTe Zhong Road, Shanghai 200131, People's Republic of China.
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Chen
authors.affiliation: WuXi AppTec (Shanghai) Co., Ltd, 288 FuTe Zhong Road, Shanghai 200131, People's Republic of China.
authors.forename: Zhengxian
authors.initials: Z
authors.lastname: Gu
authors.affiliation: WuXi AppTec (Shanghai) Co., Ltd, 288 FuTe Zhong Road, Shanghai 200131, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: WuXi AppTec (Shanghai) Co., Ltd, 288 FuTe Zhong Road, Shanghai 200131, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Shen
authors.affiliation: WuXi AppTec (Shanghai) Co., Ltd, 288 FuTe Zhong Road, Shanghai 200131, People's Republic of China.
authors.forename: Guoping
authors.initials: G
authors.lastname: Hu
authors.affiliation: WuXi AppTec (Shanghai) Co., Ltd, 288 FuTe Zhong Road, Shanghai 200131, People's Republic of China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: WuXi AppTec (Shanghai) Co., Ltd, 288 FuTe Zhong Road, Shanghai 200131, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: WuXi AppTec (Shanghai) Co., Ltd, 288 FuTe Zhong Road, Shanghai 200131, People's Republic of China.
authors.forename: Shuhui
authors.initials: S
authors.lastname: Chen
authors.affiliation: Jiangsu Kanion Pharmaceutical Co., Ltd, 58 Haichangnan Road, Lianyungang 222001, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Jiangsu Kanion Pharmaceutical Co., Ltd, 58 Haichangnan Road, Lianyungang 222001, People's Republic of China.
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Jiangsu Kanion Pharmaceutical Co., Ltd, 58 Haichangnan Road, Lianyungang 222001, People's Republic of China.
authors.forename: Qingming
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Jiangsu Kanion Pharmaceutical Co., Ltd, 58 Haichangnan Road, Lianyungang 222001, People's Republic of China.
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Chang
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, People's Republic of China.
authors.forename: Lanjun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, People's Republic of China.
authors.forename: Qixu
authors.initials: Q
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, People's Republic of China.
authors.forename: Tianwei
authors.initials: T
authors.lastname: Lin
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000097:blood / Q000138:chemical synthesis / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D029821:Enterovirus A, Human / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents
keywords: 3C protease inhibitor; Enterovirus 71; Michael acceptor