Nanomolar Inhibitors of Staphylococcus aureus Methionyl tRNA Synthetase with Potent Antibacterial Activity against Gram-Positive Pathogens

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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.