BACE1 inhibitors: a head group scan on a series of amides

Bioorg Med Chem Lett. 2013 Jul 15;23(14):4239-43. doi: 10.1016/j.bmcl.2013.05.003. Epub 2013 May 18.

Abstract

A series of amides bearing a variety of amidine head groups was investigated as BACE1 inhibitors with respect to inhibitory activity in a BACE1 enzyme as well as a cell-based assay. Determination of their basicity as well as their properties as substrates of P-glycoprotein revealed that a 2-amino-1,3-oxazine head group would be a suitable starting point for further development of brain penetrating compounds for potential Alzheimer's disease treatment.

MeSH terms

  • Alzheimer Disease / drug therapy
  • Amides / chemistry*
  • Amides / metabolism
  • Amides / therapeutic use
  • Amyloid Precursor Protein Secretases / antagonists & inhibitors*
  • Amyloid Precursor Protein Secretases / metabolism
  • Aspartic Acid Endopeptidases / antagonists & inhibitors*
  • Aspartic Acid Endopeptidases / metabolism
  • Binding Sites
  • Humans
  • Molecular Docking Simulation
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / metabolism
  • Protease Inhibitors / therapeutic use
  • Protein Binding
  • Protein Structure, Tertiary
  • Structure-Activity Relationship

Substances

  • Amides
  • Protease Inhibitors
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human