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

• Published in: Bioorganic & medicinal chemistry letters Vol. 19; no. 3; pp. 665 - 669
• Main Authors: Montgomery, Justin I., Toogood, Peter L., Hutchings, Kim M., Liu, Jia, Narasimhan, Lakshmi, Braden, Timothy, Dermyer, Michael R., Kulynych, Angela D., Smith, Yvonne D., Warmus, Joseph S., Taylor, Clarke
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.02.2009; Elsevier
• Subjects: Adenosine Triphosphate - chemistry; Aminoacyl-tRNA synthetase; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Anti-Infective Agents - chemistry; Anti-Infective Agents - pharmacology; Antibacterial; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacteria; Bacteria - enzymology; Benzyl phenyl ether; Biological and medical sciences; Chemistry, Pharmaceutical - methods; Drug Design; Drug Evaluation, Preclinical - methods; FRS; Inhibitory Concentration 50; Medical sciences; Models, Chemical; Pharmacology. Drug treatments; Phenyl Ethers - chemistry; Phenylalanine-tRNA Ligase - chemistry; Phenylalanyl-tRNA synthetase; PheRS; SAR; Structure-Activity Relationship; SAR; PheRS; FRS; Phenylalanyl-tRNA synthetase; Antibacterial; Aminoacyl-tRNA synthetase; Benzyl phenyl ether; Ether; Enzyme; Benzene derivatives; Enzyme inhibitor; In vitro; Pyridine derivatives; Structure activity relation; Ligases; Chlorine Organic compounds; Phenylalanine-tRNA ligase; Carboxamide; Benzamide derivatives; Antibacterial agent; Chemical synthesis; Carbon-oxygen ligases; Absorption Distribution Metabolisme Excretion Toxicity
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2008.12.054

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.