Nanomolar inhibitors of Staphylococcus aureus methionyl tRNA synthetase with potent antibacterial activity against gram-positive pathogens

J Med Chem. 2002 May 9;45(10):1959-62. doi: 10.1021/jm025502x.

Abstract

Potent nanomolar inhibitors of Staphylococcus aureus methionyl tRNA synthetase have been derived from a file compound high throughput screening hit. Optimized compounds show excellent antibacterial activity against staphylococcal and enterococcal pathogens, including strains resistant to clinical antibiotics. Compound 11 demonstrated in vivo efficacy in an S. aureus rat abscess infection model.

MeSH terms

  • Abscess / drug therapy
  • Abscess / microbiology
  • Animals
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Drug Resistance, Bacterial
  • Enterococcus / drug effects*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Methionine-tRNA Ligase / antagonists & inhibitors*
  • Quinolones / chemical synthesis*
  • Quinolones / chemistry
  • Quinolones / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Staphylococcus / drug effects*
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / enzymology
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Quinolones
  • Methionine-tRNA Ligase