title: Synthesis and structure-activity relationship of α-keto amides as enterovirus 71 3C protease inhibitors.
abstract: α-Keto amide derivatives as enterovirus 71 (EV71) 3C protease (3C(pro)) inhibitors have been synthesized and assayed for their biochemical and antiviral activities. structure-activity relationship (SAR) study indicated that small moieties were primarily tolerated at P1' and the introduction of para-fluoro benzyl at P2 notably improved the potency of inhibitor. Inhibitors 8v, 8w and 8x exhibited satisfactory activity (IC50=1.32±0.26μM, 1.88±0.35μM and 1.52±0.31μM, respectively) and favorable CC50 values (CC50>100μM). α-Keto amide may represent a good choice as a warhead for EV71 3C(pro) inhibitor.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, PR China.
authors.forename: Debin
authors.initials: D
authors.lastname: Zeng
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, PR China.
authors.forename: Yuying
authors.initials: Y
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, PR China.
authors.forename: Quandeng
authors.initials: Q
authors.lastname: Nie
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, PR China.
authors.forename: Zhengjie
authors.initials: Z
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, PR China.
authors.forename: Yaxin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, PR China. Electronic address: shanglq@nankai.edu.cn.
authors.forename: Luqing
authors.initials: L
authors.lastname: Shang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, PR China. Electronic address: zheng_yin@nankai.edu.cn.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yin
mesh_terms: D000577:Amides / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D029821:Enterovirus A, Human / Q000187:drug effects* / Q000201:enzymology*; D004769:Enterovirus Infections / Q000188:drug therapy / Q000821:virology; D006801:Humans; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000037:antagonists & inhibitors
chemical_list: D000577:Amides; D000998:Antiviral Agents; D011480:Protease Inhibitors; D014764:Viral Proteins
keywords: 3C protease; Enterovirus 71; Inhibitor; Structure activity relationship; α-Keto amide