Synthesis and optimization of thiadiazole derivatives as a novel class of substrate competitive c-Jun N-terminal kinase inhibitors

Bioorg Med Chem. 2010 Jan 15;18(2):590-6. doi: 10.1016/j.bmc.2009.12.013. Epub 2009 Dec 11.

Abstract

A series of thiadiazole derivatives has been designed as potential allosteric, substrate competitive inhibitors of the protein kinase JNK. We report on the synthesis, characterization and evaluation of a series of compounds that resulted in the identification of potent and selective JNK inhibitors targeting its JIP-1 docking site.

Publication types

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

MeSH terms

  • Drug Design
  • HeLa Cells
  • Humans
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • Models, Molecular
  • Molecular Structure
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Thiadiazoles / chemical synthesis*
  • Thiadiazoles / chemistry
  • Thiadiazoles / pharmacology*

Substances

  • Protein Kinase Inhibitors
  • Thiadiazoles
  • JNK Mitogen-Activated Protein Kinases