Inhibition of Dengue virus and West Nile virus proteases by click chemistry-derived benz[d]isothiazol-3(2H)-one derivatives

Bioorg Med Chem. 2012 Feb 1;20(3):1213-21. doi: 10.1016/j.bmc.2011.12.047. Epub 2011 Dec 30.

Abstract

Two click chemistry-derived focused libraries based on the benz[d]isothiazol-3(2H)-one scaffold were synthesized and screened against Dengue virus and West Nile virus NS2B-NS3 proteases. Several compounds (4l, 7j-n) displayed noteworthy inhibitory activity toward Dengue virus NS2B-NS3 protease in the absence and presence of added detergent. These compounds could potentially serve as a launching pad for a hit-to-lead optimization campaign.

Publication types

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

MeSH terms

  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology*
  • Click Chemistry
  • Dengue / drug therapy
  • Dengue / enzymology
  • Dengue Virus / drug effects
  • Dengue Virus / enzymology*
  • Humans
  • Models, Molecular
  • Peptide Hydrolases / metabolism*
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / pharmacology*
  • Thiazoles / chemistry
  • Thiazoles / pharmacology
  • West Nile Fever / drug therapy
  • West Nile Fever / enzymology
  • West Nile virus / drug effects
  • West Nile virus / enzymology*

Substances

  • Antiviral Agents
  • Protease Inhibitors
  • Thiazoles
  • Peptide Hydrolases