Discovery and SAR of benzyl phenyl ethers as inhibitors of bacterial phenylalanyl-tRNA synthetase

Justin I Montgomery; Peter L Toogood; Kim M Hutchings; Jia Liu; Lakshmi Narasimhan; Timothy Braden; Michael R Dermyer; Angela D Kulynych; Yvonne D Smith; Joseph S Warmus; Clarke Taylor

doi:10.1016/j.bmcl.2008.12.054

Discovery and SAR of benzyl phenyl ethers as inhibitors of bacterial phenylalanyl-tRNA synthetase

Bioorg Med Chem Lett. 2009 Feb 1;19(3):665-9. doi: 10.1016/j.bmcl.2008.12.054. Epub 2008 Dec 24.

Authors

Justin I Montgomery¹, Peter L Toogood, Kim M Hutchings, Jia Liu, Lakshmi Narasimhan, Timothy Braden, Michael R Dermyer, Angela D Kulynych, Yvonne D Smith, Joseph S Warmus, Clarke Taylor

Affiliation

¹ Pfizer Global Research and Development, Michigan Laboratories, Ann Arbor Campus, 2800 Plymouth Road, Ann Arbor, MI 48105, USA. [email protected]

PMID: 19121937
DOI: 10.1016/j.bmcl.2008.12.054

Abstract

A series of benzyl phenyl ethers (BPEs) is described that displays potent inhibition of bacterial phenylalanyl-tRNA synthetase. The synthesis, SAR, and select ADMET data are provided.

MeSH terms

Adenosine Triphosphate / chemistry
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology
Anti-Infective Agents / chemistry
Anti-Infective Agents / pharmacology
Bacteria / enzymology*
Chemistry, Pharmaceutical / methods*
Drug Design
Drug Evaluation, Preclinical / methods
Inhibitory Concentration 50
Models, Chemical
Phenyl Ethers / chemistry*
Phenylalanine-tRNA Ligase / chemistry*
Structure-Activity Relationship

Substances

Anti-Bacterial Agents
Anti-Infective Agents
Phenyl Ethers
Adenosine Triphosphate
Phenylalanine-tRNA Ligase