Discovery of oxadiazoyl tertiary carbinamine inhibitors of beta-secretase (BACE-1)

J Med Chem. 2006 Dec 14;49(25):7270-3. doi: 10.1021/jm061046r.

Abstract

We describe the discovery and optimization of tertiary carbinamine derived inhibitors of the enzyme beta-secretase (BACE-1). These novel non-transition-state-derived ligands incorporate a single primary amine to interact with the catalytic aspartates of the target enzyme. Optimization of this series provided inhibitors with intrinsic and functional potency comparable to evolved transition state isostere derived inhibitors of BACE-1.

MeSH terms

  • Amyloid Precursor Protein Secretases / antagonists & inhibitors*
  • Amyloid Precursor Protein Secretases / chemistry*
  • Aniline Compounds / chemical synthesis*
  • Aniline Compounds / chemistry
  • Crystallography, X-Ray
  • Models, Molecular
  • Oxadiazoles / chemical synthesis*
  • Oxadiazoles / chemistry

Substances

  • Aniline Compounds
  • Oxadiazoles
  • Amyloid Precursor Protein Secretases