- Design, synthesis and antiviral efficacy of a series of potent chloropyridyl ester-derived SARS-CoV 3CLpro inhibitors.
Design, synthesis and antiviral efficacy of a series of potent chloropyridyl ester-derived SARS-CoV 3CLpro inhibitors.
Bioorganic & medicinal chemistry letters (2008-09-18)
Arun K Ghosh, Gangli Gong, Valerie Grum-Tokars, Debbie C Mulhearn, Susan C Baker, Melissa Coughlin, Bellur S Prabhakar, Katrina Sleeman, Michael E Johnson, Andrew D Mesecar
PMID18796354
ABSTRACT
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 microM. Molecular docking studies have provided possible binding modes of these inhibitors.
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