Identification of potent type I MetAP inhibitors by simple bioisosteric replacement. Part 1: Synthesis and preliminary SAR studies of thiazole-4-carboxylic acid thiazol-2-ylamide derivatives

Bioorg Med Chem Lett. 2005 Aug 15;15(16):3732-6. doi: 10.1016/j.bmcl.2005.05.055.

Abstract

A series of thiazole-4-carboxylic acid thiazol-2-ylamide (TCAT, 4) derivatives were designed and synthesized according to simple bioisosteric replacement from previously reported pyridine-2-carboxylic acid thiazol-2-ylamide (PCAT) MetAP inhibitors. The preliminary SAR studies demonstrated that these TCAT series of compounds showed different activity and selectivity compared with those of the corresponding PCAT compounds. These findings provide useful information for the design and discovery of more potent inhibitors of type I MetAPs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopeptidases / antagonists & inhibitors*
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology*
  • Escherichia coli / enzymology
  • Methionyl Aminopeptidases
  • Molecular Structure
  • Saccharomyces cerevisiae / enzymology
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*
  • Thioamides / chemical synthesis
  • Thioamides / chemistry
  • Thioamides / pharmacology*

Substances

  • Enzyme Inhibitors
  • Thiazoles
  • Thioamides
  • Aminopeptidases
  • Methionyl Aminopeptidases