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

  • Bioorg Med Chem Lett. 2008 Oct 15;18(20):5684-8. doi: 10.1016/j.bmcl.2008.08.082.
Arun K Ghosh  1 ,  Gangli Gong ,  Valerie Grum-Tokars ,  Debbie C Mulhearn ,  Susan C Baker ,  Melissa Coughlin ,  Bellur S Prabhakar ,  Katrina Sleeman ,  Michael E Johnson ,  Andrew D Mesecar
Affiliations
  • 1. Department of Chemistry, Purdue University, 560 Oval drive, West Lafayette, IN 47907, USA. [email protected]
PMID: 18796354 DOI: 10.1016/j.bmcl.2008.08.082
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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