The discovery of a potent and selective lethal factor inhibitor for adjunct therapy of anthrax infection

Bioorg Med Chem Lett. 2006 Feb 15;16(4):964-8. doi: 10.1016/j.bmcl.2005.10.088. Epub 2005 Dec 9.

Abstract

A potent and selective anthrax LF inhibitor 40, (2R)-2-[(4-fluoro-3-methylphenyl)sulfonylamino]-N-hydroxy-2-(tetrahydro-2H-pyran-4-yl)acetamide, was identified through SAR study of a high throughput screen lead. It has an IC50 of 54 nM in the enzyme assay and an IC50 of 210 nM in the macrophage cytotoxicity assay. Compound 40 is also effective in vivo in several animal model studies.

MeSH terms

  • Animals
  • Anthrax / drug therapy
  • Anthrax / prevention & control
  • Antigens, Bacterial
  • Bacterial Toxins / antagonists & inhibitors*
  • Biological Availability
  • Dogs
  • Drug Evaluation, Preclinical
  • Macaca mulatta
  • Metalloproteases / antagonists & inhibitors
  • Mice
  • Molecular Structure
  • Pyrans / administration & dosage
  • Pyrans / chemical synthesis
  • Pyrans / pharmacology*
  • Rabbits
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • (2R)-2-((4-fluoro-3-methylphenyl)sulfonylamino)-N-hydroxy-2-(tetrahydro-2H-pyran-4-yl)acetamide
  • Antigens, Bacterial
  • Bacterial Toxins
  • Pyrans
  • anthrax toxin
  • Metalloproteases