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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)5684-5688
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume18
Issue number20
DOIs
StatePublished - Oct 15 2008

Keywords

  • Antiviral
  • Ester
  • Inhibitor
  • SARS 3CLpro
  • Synthesis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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