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Research Letter
Synthesis, in vitro Biological Evaluation and Molecular Docking Studies of Benzimidamides as Potential BACE1 Inhibitors
Article first published online: 10 SEP 2012
DOI: 10.1111/cbdd.12016
© 2012 John Wiley & Sons A/S
Additional Information
How to Cite
Niu, Y., Gao, H., Xu, F., Wang, C., Liu, P., Yang, G., Sun, Q. and Xu, P. (2012), Synthesis, in vitro Biological Evaluation and Molecular Docking Studies of Benzimidamides as Potential BACE1 Inhibitors. Chemical Biology & Drug Design, 80: 775–780. doi: 10.1111/cbdd.12016
Publication History
- Issue published online: 5 OCT 2012
- Article first published online: 10 SEP 2012
- Accepted manuscript online: 7 AUG 2012 09:44AM EST
- Received 6 February 2012, revised 6 July 2012 and accepted for publication 30 July 2012
Keywords:
- Alzheimer’s disease;
- BACE1 inhibitors;
- benzimidamide;
- docking
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.