Part 2. Notch-sparing γ-secretase inhibitors: The study of novel γ-amino naphthyl alcohols

Bioorg Med Chem Lett. 2016 May 1;26(9):2133-7. doi: 10.1016/j.bmcl.2016.03.042. Epub 2016 Mar 15.

Abstract

One therapeutic approach for Alzheimer's disease is to inhibit the cleavage of the amyloid precursor protein (APP) by γ-secretase. At the beginning of a series of studies from our laboratories, a series of novel γ-amino alcohols (1) were found to possess γ-secretase inhibitory activity and Notch-sparing effects. A new one-pot synthesis of γ-amino alcohols and the structure-activity relationship (SAR) of these analogs will be discussed.

Keywords: Alzheimer’s disease; Aβ production; Notch-processing; γ-Amino alcohols; γ-Secretase inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Alcohols / chemical synthesis
  • Amino Alcohols / pharmacology
  • Amyloid Precursor Protein Secretases / antagonists & inhibitors*
  • Amyloid beta-Peptides / antagonists & inhibitors
  • Animals
  • Humans
  • Microsomes, Liver / metabolism
  • Naphthalenes / chemical synthesis
  • Naphthalenes / pharmacology
  • Peptide Fragments / antagonists & inhibitors
  • Propanolamines / chemical synthesis
  • Propanolamines / pharmacology*
  • Protease Inhibitors / chemical synthesis
  • Protease Inhibitors / pharmacology*
  • Rats
  • Receptor, Notch1 / metabolism*
  • Structure-Activity Relationship

Substances

  • Amino Alcohols
  • Amyloid beta-Peptides
  • NOTCH1 protein, human
  • Naphthalenes
  • Notch1 protein, rat
  • Peptide Fragments
  • Propanolamines
  • Protease Inhibitors
  • Receptor, Notch1
  • ZM39923
  • amyloid beta-protein (1-42)
  • Amyloid Precursor Protein Secretases