Design, synthesis and antiviral efficacy of a series of potent chloropyridyl ester-derived SARS-CoV 3CLpro inhibitors

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:18

Article

Ghosh, Arun K.^1,2  Gong, Gangli^1,2  Grum-Tokars, Valerie³  Mulhearn, Debbie C.³  Baker, Susan C.⁴  Coughlin, Melissa⁵  Prabhakar, Bellur S.⁵  Sleeman, Katrina⁴  Johnson, Michael E.³  Mesecar, Andrew D.³ 

[1] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA

[2] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA

[3] Univ Illinois, Ctr Pharmaceut Biotechnol, Dept Med Chem & Pharmacognosy, Chicago, IL 60607 USA

[4] Loyola Univ Chicago, Stritch Sch Med, Dept Microbiol & Immunol, Maywood, IL USA

[5] Univ Illinois, Dept Microbiol & Immunol, Chicago, IL 60607 USA

关键词: synthesis;    SARS 3CLpro;    ester;    antiviral;    inhibitor;   

DOI  :  10.1016/j.bmcl.2008.08.082

来源: Elsevier

【 摘 要 】

Design, synthesis and biological evaluation of a series of 5-chloropyridine ester-derived severe acute respiratory syndrome-coronavirus chymotrypsin-like protease inhibitors is described. Position of the carboxylate functionality is critical to potency. Inhibitor 10 with a 5-chloropyridinyl ester at position 4 of the indole ring is the most potent inhibitor with a SARS-CoV 3CLpro IC(50) value of 30 nM and an antiviral EC(50) value of 6.9 mu M. Molecular docking studies have provided possible binding modes of these inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.

【 授权许可】

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