A small chemical library of 2-aminoimidazole derivatives as BACE-1 inhibitors: Structure-based design, synthesis, and biological evaluation

Eur J Med Chem. 2012 Feb:48:206-13. doi: 10.1016/j.ejmech.2011.12.016. Epub 2011 Dec 16.

Abstract

In this work, we report a rational structure-based approach aimed at the discovery of new 2-aminoimidazoles as β-secretase inhibitors. Taking advantage of a microwave-assisted synthetic protocol, a small library of derivatives was obtained and biologically evaluated. Two compounds showed promising activities in both enzymatic and cellular assays. Moreover, one of them exhibited the capability to cross the blood-brain barrier as assessed by the parallel artificial membrane permeability assay.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / enzymology
  • Alzheimer Disease / metabolism
  • Amyloid Precursor Protein Secretases / antagonists & inhibitors
  • Amyloid Precursor Protein Secretases / metabolism*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Cell Survival / drug effects
  • Chickens
  • Humans
  • Imidazoles / chemical synthesis
  • Imidazoles / chemistry*
  • Imidazoles / pharmacology*
  • Inhibitory Concentration 50
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Neurons
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry*
  • Small Molecule Libraries / pharmacology*
  • Spectrometry, Mass, Electrospray Ionization
  • Spectroscopy, Fourier Transform Infrared
  • Structure-Activity Relationship

Substances

  • Amyloid beta-Peptides
  • Imidazoles
  • Small Molecule Libraries
  • Amyloid Precursor Protein Secretases