Design and synthesis of an aminopiperidine series of γ-secretase modulators

Bioorg Med Chem Lett. 2014 Jan 1;24(1):378-81. doi: 10.1016/j.bmcl.2013.10.063. Epub 2013 Nov 6.

Abstract

The design, synthesis, and SAR of cyclic diamines as novel γ secretase modulators (GSMs) are presented in this Letter. Starting from information in the literature and in-house cyclic diamines library, we have found a 3(S)-aminopiperidine as a potent structure for lowering Aβ42 production both in vitro and in vivo.

Keywords: Alzheimer’s disease; Amyloid β peptide; Piperidine; γ-Secretase inhibitor; γ-Secretase modulator.

MeSH terms

  • Amyloid Precursor Protein Secretases / metabolism*
  • Amyloid beta-Peptides / antagonists & inhibitors
  • Amyloid beta-Peptides / biosynthesis
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Humans
  • Molecular Structure
  • Peptide Fragments / antagonists & inhibitors
  • Peptide Fragments / biosynthesis
  • Piperidines / chemical synthesis
  • Piperidines / chemistry
  • Piperidines / pharmacology*
  • Structure-Activity Relationship

Substances

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