A novel series of potent gamma-secretase inhibitors based on a benzobicyclo[4.2.1]nonane core

Bioorg Med Chem Lett. 2005 Jan 17;15(2):373-8. doi: 10.1016/j.bmcl.2004.10.062.

Abstract

A new series of gamma-secretase inhibitors was developed from an in-house screening hit based on a benzobicyclo[4.2.1]nonane core. Lead optimisation studies led to the development of a series of potent inhibitors and in vivo efficacy was demonstrated.

MeSH terms

  • Alkanes / chemical synthesis*
  • Alkanes / pharmacology
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Amides / chemistry
  • Amines / chemistry
  • Amyloid Precursor Protein Secretases
  • Animals
  • Aspartic Acid Endopeptidases
  • Brain / drug effects*
  • Brain / metabolism
  • Endopeptidases / metabolism*
  • Heterocyclic Compounds / chemistry*
  • Mice
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / pharmacology
  • Structure-Activity Relationship

Substances

  • Alkanes
  • Amides
  • Amines
  • Heterocyclic Compounds
  • Protease Inhibitors
  • Amyloid Precursor Protein Secretases
  • Endopeptidases
  • Aspartic Acid Endopeptidases
  • Bace1 protein, mouse
  • nonane