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.
Copyright © 2014 Elsevier Masson SAS. All rights reserved.
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