Discovery of fused 5,6-bicyclic heterocycles as γ-secretase modulators

Bioorg Med Chem Lett. 2011 Jan 15;21(2):664-9. doi: 10.1016/j.bmcl.2010.12.012. Epub 2010 Dec 13.

Abstract

We herein report the discovery of four series of fused 5,6-bicyclic heterocycles as γ-secretase modulators. Synthesis and SAR of these series are discussed. These compounds represent a new class of γ-secretase modulators that demonstrate moderate to good in vitro potency in inhibiting Aβ(42) production.

MeSH terms

  • Alzheimer Disease / drug therapy
  • Amyloid Precursor Protein Secretases / metabolism*
  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Bridged Bicyclo Compounds, Heterocyclic / chemistry*
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacokinetics
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
  • Humans
  • Rats
  • Structure-Activity Relationship

Substances

  • Amyloid beta-Peptides
  • Bridged Bicyclo Compounds, Heterocyclic
  • Amyloid Precursor Protein Secretases