Thiazole-diamides as potent gamma-secretase inhibitors

Bioorg Med Chem Lett. 2007 Oct 15;17(20):5518-22. doi: 10.1016/j.bmcl.2007.08.035. Epub 2007 Aug 19.

Abstract

The thiazole-diamide series (1) has been identified as highly potent gamma-secretase inhibitors. Several representative compounds showed IC(50) values of <0.3 nM. The synthesis and SAR, as well as a radiolabeled synthesis of [(3)H]-2a, are described.

MeSH terms

  • Alkylation
  • Amination
  • Amyloid Precursor Protein Secretases / antagonists & inhibitors*
  • Amyloid Precursor Protein Secretases / metabolism
  • Cell-Free System
  • Diamide / chemical synthesis
  • Diamide / chemistry*
  • Diamide / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Structure-Activity Relationship
  • Thiazoles / chemistry*

Substances

  • Thiazoles
  • Diamide
  • Amyloid Precursor Protein Secretases