3,4-Fused cyclohexyl sulfones as gamma-secretase inhibitors

Bioorg Med Chem Lett. 2006 Jun 1;16(11):3073-7. doi: 10.1016/j.bmcl.2005.12.083. Epub 2006 Apr 17.

Abstract

The 3,4-fused sulfamides, sulfonamides and sulfone have been identified as highly potent gamma-secretase inhibitors. Evaluation of the SAR of substitution within these series has allowed the identification of a range of compounds which significantly reduce brain A beta in transgenic mouse models and thus have potential as possible treatments for Alzheimer's disease.

MeSH terms

  • Amyloid Precursor Protein Secretases
  • Animals
  • Aspartic Acid Endopeptidases
  • Crystallography, X-Ray
  • Cyclization
  • Endopeptidases / metabolism*
  • Models, Molecular
  • Molecular Structure
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • Rats
  • Structure-Activity Relationship
  • Sulfones / chemical synthesis
  • Sulfones / chemistry*
  • Sulfones / pharmacology*

Substances

  • Protease Inhibitors
  • Sulfones
  • Amyloid Precursor Protein Secretases
  • Endopeptidases
  • Aspartic Acid Endopeptidases
  • Bace1 protein, mouse