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

作者：Ghosh Arun K^*; Gong Gangli; Grum Tokars Valerie; Mulhearn Debbie C; Baker Susan C; Coughlin Melissa; Prabhakar Bellur S; Sleeman Katrina; Johnson Michael E; Mesecar Andrew D

来源：Bioorganic & Medicinal Chemistry Letters, 2008, 18(20): 5684-5688.

DOI：10.1016/j.bmcl.2008.08.082

• synthesis
• SARS 3CLpro
• ester
• antiviral
• inhibitor

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.

• 出版日期2008-10-15