Inhibitors of type I MetAPs containing pyridine-2-carboxylic acid thiazol-2-ylamide. Part 2: SAR studies on the pyridine ring 3-substituent

Bioorg Med Chem Lett. 2005 Feb 1;15(3):639-44. doi: 10.1016/j.bmcl.2004.11.035.

Abstract

Systematic SAR studies on the pyridine ring 3-substituent of PCAT, an inhibitor of EcMetAP1 and ScMetAP1, revealed that 3-substituents have different selectivity for EcMetAP1 and ScMetAP1. The selective inhibitors of type I MetAP are useful tools for investigating the detailed interactions between the enzymes and their inhibitors. In addition, these findings provide useful information for the design and discovery of more potent inhibitors of type I MetAPs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aminopeptidases / antagonists & inhibitors*
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / pharmacology
  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / pharmacology
  • Bacterial Proteins / antagonists & inhibitors
  • Escherichia coli / enzymology
  • Humans
  • Inhibitory Concentration 50
  • Methionyl Aminopeptidases
  • Pyridines / chemical synthesis
  • Pyridines / pharmacology
  • Salmonella typhimurium / enzymology
  • Structure-Activity Relationship
  • Thioamides / chemical synthesis*
  • Thioamides / pharmacology

Substances

  • Anti-Bacterial Agents
  • Antifungal Agents
  • Bacterial Proteins
  • Pyridines
  • Thioamides
  • Aminopeptidases
  • Methionyl Aminopeptidases