Potent and Selective Inhibitors of Bacterial Methionyl tRNA Synthetase Derived from an Oxazolone—Dipeptide Scaffold

The preparation and structure–activity relationships (SARs) of potent and selective small molecule inhibitors of bacterial methionyl-tRNA synthetase (MetRS) derived from an oxazolone–dipeptide scaffold are described. Examples combine Staphylococcus aureus MetRS (SaMetRS) potency with selectivity over human MetRS. As a result of the SAR expansion compound 14a was identified, as a potent SaMetRS inhibitor (IC50=18 nM) having moderate inhibition of MetRS derived from Enterococci faecalis (IC50=3.51 μM).