4-Oxo-1,4-dihydro-quinoline-3-carboxamides as BACE-1 inhibitors: synthesis, biological evaluation and docking studies

Eur J Med Chem. 2014 May 22:79:413-21. doi: 10.1016/j.ejmech.2014.04.025. Epub 2014 Apr 12.

Abstract

In this work, we report a series of new 4-oxo-1,4-dihydro-quinoline-3-carboxamide derivatives as β-secretase (BACE-1) inhibitors. Supported by docking study, a small library of derivatives were designed, synthesized and biologically evaluated in vitro. The studies revealed that the most potent analog 14e (IC50 = 1.89 μM) with low cellular cytotoxicity and high predicted blood brain barrier permeability, could serve as a good structure for further modification.

Keywords: 4-Oxo-1,4-dihydro-quinoline-3-carboxamide; Alzheimer's disease; BACE-1 inhibitors; Docking study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid Precursor Protein Secretases / antagonists & inhibitors*
  • Amyloid Precursor Protein Secretases / metabolism
  • Aspartic Acid Endopeptidases / antagonists & inhibitors*
  • Aspartic Acid Endopeptidases / metabolism
  • Dose-Response Relationship, Drug
  • HEK293 Cells
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Quinolines / chemical synthesis
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Structure-Activity Relationship

Substances

  • 4-oxo-1,4-dihydroquinoline-3-carboxamide
  • Quinolines
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human