Quinazolinones as γ-secretase modulators

Bioorg Med Chem Lett. 2011 Jan 15;21(2):773-6. doi: 10.1016/j.bmcl.2010.11.111. Epub 2010 Nov 26.

Abstract

Synthesis, SAR and evaluation of styrenyl quinazolinones as novel gamma secretase modulators are presented in this communication. Starting from literature and in-house leads we evaluated a range of quinazolinones which showed good modulation of γ-secretase activity.

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / enzymology
  • Alzheimer Disease / metabolism
  • Amyloid Precursor Protein Secretases / metabolism*
  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Cell Line
  • Humans
  • Inhibitory Concentration 50
  • Peptide Fragments / antagonists & inhibitors
  • Peptide Fragments / metabolism
  • Protein Binding
  • Quinazolinones / chemistry*
  • Quinazolinones / pharmacokinetics
  • Quinazolinones / pharmacology*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • Quinazolinones
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)
  • Amyloid Precursor Protein Secretases