Synthesis and structure–activity relationship of α-keto amides as enterovirus 71 3C protease inhibitors. Issue 7 (1st April 2016)

• Record Type: Journal Article
• Authors: Zeng, Debin; Ma, Yuying; Zhang, Rui; Nie, Quandeng; Cui, Zhengjie; Wang, Yaxin; Shang, Luqing; Yin, Zheng
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 7(2016)
• Page Start: 1762
• Page End: 1766
• Publication Date: 2016-04-01
• Subjects: KTPDJDPOVFPGET-YFAIDLNWSA-N -- XVKCKIIDQMAPFP-LZIYWEKBSA-N -- YQWARDIIWHIJIP-KXCHGZFJSA-N -- ZLXSSWZMXAAGDQ-KXCHGZFJSA-N -- KKQDWGGWDSPZOI-DOAZHDKUSA-N -- WSPLMKHQVURNSA-QRCURLSBSA-N -- IUGNEROYHYWMAE-AUBKUYCASA-N -- DSGJXYDIIYIOSZ-AUBKUYCASA-N -- LSKIMJNZNHSHNZ-YKAJZYPISA-N -- XPOSSHHQWWHJLB-DFSKWLJZSA-N -- NSOOMFCHVKZGTL-DOAZHDKUSA-N -- BOYIPJKJEWHIKC-DFGBAKFCSA-N -- DBUYZTHGACNVGC-JUIWSWHPSA-N -- AXEMWWJLLYVWSN-QIDREQHXSA-N -- XCLKFGFGJOYONI-FTGFBZEVSA-N -- REIMJGPXWBUGES-URFKUNIZSA-N -- JWJHNNIPFHRVQA-JVLZUOAVSA-N -- VMPBMDOOOUZJKU-RIRHMXKASA-N -- RYABBKZHRSIAES-OMSNZGBCSA-N -- MSXGVONLPBLEIA-QXDDGKQISA-N -- MMMIMYZTSTZWBB-HZGIJGLDSA-N -- HKQPXRPSKQCLFR-HZGIJGLDSA-N -- GANQHNNHDLXVBM-BBNQEMJNSA-N -- UHERLXZFFAVXKP-DJGDUWQLSA-N -- MSZSQDDPWKOMHG-XWGVYQGASA-N -- OGVXMZKHWJVMBB-IHPCNDPISA-N -- HUXUITBXNLHPSP-BVSLBCMMSA-N -- QVSNDXZBFGRALK-SZMVWBNQSA-N -- KXABQHWYIMGPQO-BVSLBCMMSA-N -- TWTYFLVVPCOLJF-SZMVWBNQSA-N -- LCXSFSYPOLDSQR-BVSLBCMMSA-N -- MJZFMPXZPMFPPB-SZMVWBNQSA-N; Enterovirus 71 -- 3C protease -- α-Keto amide -- Inhibitor -- Structure activity relationship; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.02.039
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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. Inhibitors8v, 8w and8x exhibited satisfactory activity (IC50 = 1.32 ± 0.26 μM, 1.88 ± 0.35 μM and 1.52 ± 0.31 μM, respectively) and favorable CC50 values (CC50 > 100 μM). α-Keto amide may represent a good choice as a warhead for EV71 3C pro inhibitor.