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

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 IC50 value of 30 nM and an antiviral EC50 value of 6.9 μM. Molecular docking studies have provided possible binding modes of these inhibitors.

Graphical abstractDesign, synthesis and biological evaluation of a series of chloropyridyl ester-derived SARS-CoV 3CLpro Inhibitors are described Inhibitors 10 has shown potent activity in both enzyme inhibitory and antiviral assaysFigure optionsDownload full-size imageDownload as PowerPoint slide