Design and synthesis of dipeptidyl glutaminyl fluoromethyl ketones as potent severe acute respiratory syndrome coronovirus (SARS-CoV) inhibitors

J Med Chem. 2006 Feb 9;49(3):1198-201. doi: 10.1021/jm0507678.

Abstract

This paper describes the design and synthesis of dipeptidyl N,N-dimethyl glutaminyl fluoromethyl ketones (fmk) as severe acute respiratory syndrome coronovirus (SARS-CoV) inhibitors. The compounds were tested against SARS-CoV-induced cell death in Vero or CaCo2 cells as a measurement of the inhibiting effects of the compounds on the replication of the virus. Z-Leu-Gln(NMe(2))-fmk (6a) was found to be a potent inhibitor with low toxicity in cells, protecting cells with an EC(50) value of 2.5 microM and exhibiting a selectivity index of >40.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Caco-2 Cells
  • Cell Death / drug effects
  • Chlorocebus aethiops
  • Dipeptides / chemical synthesis*
  • Dipeptides / chemistry
  • Dipeptides / pharmacology
  • Drug Design
  • Humans
  • Severe acute respiratory syndrome-related coronavirus / drug effects*
  • Vero Cells
  • Virus Replication

Substances

  • Antiviral Agents
  • Dipeptides
  • benzyloxycarbonyl-leucyl-N,N-dimethylglutamine fluoromethyl ketone