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

Bioorg Med Chem Lett. 2004 Mar 8;14(5):1339-42. doi: 10.1016/j.bmcl.2003.11.081.

Abstract

We have identified a series of spirocyclic furan and pyrrolidine inhibitors of Enterococcus 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.

Publication types

  • Comparative Study

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Furans / chemistry
  • Furans / pharmacology
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds / pharmacology
  • Phenylalanine-tRNA Ligase / antagonists & inhibitors*
  • Phenylalanine-tRNA Ligase / metabolism
  • Pyrrolidines / chemistry
  • Pyrrolidines / pharmacology
  • RNA, Bacterial / antagonists & inhibitors*
  • RNA, Bacterial / chemistry
  • RNA, Bacterial / metabolism

Substances

  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Furans
  • Heterocyclic Compounds
  • Pyrrolidines
  • RNA, Bacterial
  • Phenylalanine-tRNA Ligase