Synthesis,in vitroBiological Evaluation and Molecular Docking Studies of Benzimidamides as Potential BACE1 Inhibitors
Authors:
Open Access
- 7 August 2012
- journal article
- research article
- Published by Wiley in Chemical Biology & Drug Design
- Vol. 80 (5) , 775-780
Abstract
A series of 3, 5-disubstituted benzimidamides were synthesized and biologically evaluated as potential BACE1 inhibitors. Both the targeted compounds (benzimidamides) and the synthetic intermediates (benzonitriles) were tested for their BACE1 inhibitory activities in a cell-free FRET assay. All the synthesized benzimidamides were active as BACE1 inhibitors and compound 6d showed the lowest IC50 value of 3.35 μm. Molecular docking study proposed a binding mode, which would help to the further optimization on 6d to achieve more potent, BBB penetrant BACE1 inhibitors.Keywords
This publication has 21 references indexed in Scilit:
- Sequential Virtual Screening Approach to the Identification of Small Organic Molecules as Potential BACE-1 InhibitorsChemical Biology & Drug Design, 2011
- Identification of a sub-micromolar, non-peptide inhibitor of β-secretase with low neural cytotoxicity through in silico screeningBioorganic & Medicinal Chemistry Letters, 2010
- Hybrid Structure-Based Virtual Screening Protocol for the Identification of Novel BACE1 InhibitorsJournal of Chemical Information and Modeling, 2009
- Second Generation of Hydroxyethylamine BACE-1 Inhibitors: Optimizing Potency and Oral BioavailabilityJournal of Medicinal Chemistry, 2008
- Protease inhibitors as potential disease-modifying therapeutics for Alzheimer’s diseaseExpert Opinion on Investigational Drugs, 2005
- Design and Synthesis of Hydroxyethylene-Based Peptidomimetic Inhibitors of Human β-SecretaseJournal of Medicinal Chemistry, 2003
- Improved protein–ligand docking using GOLDProteins: Structure, Function, and Bioinformatics, 2003
- The Amyloid Hypothesis of Alzheimer's Disease: Progress and Problems on the Road to TherapeuticsScience, 2002
- BACE Maps to Chromosome 11 and a BACE Homolog, BACE2 , Reside in the Obligate Down Syndrome Region of Chromosome 21Science, 1999
- β-Secretase Cleavage of Alzheimer's Amyloid Precursor Protein by the Transmembrane Aspartic Protease BACEScience, 1999