Potent and selective inhibitors of bacterial methionyl tRNA synthetase derived from an oxazolone–dipeptide scaffold

Abstract

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 (IC 50=18 nM) having moderate inhibition of MetRS derived from Enterococci faecalis (IC 50=3.51 μM).