A series of spirocyclic analogues as potent inhibitors of bacterial phenylalanyl-tRNA synthetases

We have identified a series of spirocyclic furan and pyrrolidine inhibitors of Enterococeus faecalis and Staphylococcus aureus phenylalanyl-tRNA synthetases. The most potent analogue 1b showed IC50=5 nM (E. faecalis PheRS) and IC50=2 nM (S. aureus PheRS) with high selectivity over the human enzyme. The crystal X-ray structure of analogue 1b was determined.