Potent and selective isophthalamide S2 hydroxyethylamine inhibitors of BACE1

Bioorg Med Chem Lett. 2007 Jun 15;17(12):3378-83. doi: 10.1016/j.bmcl.2007.03.096. Epub 2007 Apr 3.

Abstract

The design and synthesis of a novel series of potent BACE1 hydroxyethylamine inhibitors. These inhibitors feature hydrogen bonding substituents at the C-5 position of the isophthalamide ring with improved selectivity over cathepsin D.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amyloid Precursor Protein Secretases / antagonists & inhibitors*
  • Animals
  • Aspartic Acid Endopeptidases / antagonists & inhibitors*
  • Cathepsin D / antagonists & inhibitors
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology*
  • Ethylamines / chemical synthesis
  • Ethylamines / pharmacology*
  • Humans
  • Hydrogen Bonding
  • Ifosfamide / analogs & derivatives
  • Ifosfamide / chemical synthesis
  • Ifosfamide / pharmacology*
  • Mice
  • Mice, Knockout
  • Models, Chemical
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Ethylamines
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human
  • Bace1 protein, mouse
  • Cathepsin D
  • Ifosfamide