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Synthesis and Biological Activity of Substituted Urea and Thiourea Derivatives Containing 1,2,4-Triazole Moieties
Molecules 2013, 18(3), 3577-3594; doi:10.3390/molecules18033577
Article

Design, Synthesis and Evaluation of 3-(2-Aminoheterocycle)-4-benzyloxyphenylbenzamide Derivatives as BACE-1 Inhibitors

1, 1, 1, 2, 2, 1,3, 4, 4, 1 and 1,*
Received: 17 February 2013 / Revised: 15 March 2013 / Accepted: 18 March 2013 / Published: 20 March 2013
(This article belongs to the Section Medicinal Chemistry)
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Abstract

Three series of 3-(2-aminoheterocycle)-4-benzyloxyphenylbenzamide derivatives, 2-aminooxazoles, 2-aminothiazoles, and 2-amino-6H-1,3,4-thiadizines were designed, synthesized and evaluated as β-secretase (BACE-1) inhibitors. Preliminary structure-activity relationships revealed that the existence of a 2-amino-6H-1,3,4-thiadizine moiety and α-naphthyl group were favorable for BACE-1 inhibition. Among the synthesized compounds, 5e exhibited the most potent BACE-1 inhibitory activity, with an IC50 value of 9.9 μΜ and it exhibited high brain uptake potential in Madin-Darby anine kidney cell lines (MDCK) and a Madin-Darby canine kidney-multidrug resistance 1 (MDCK-MDR1) model.
Keywords: BACE-1 inhibitor; 2-amino-6H-1,3,4-thiadizine; blood-brain barrier permeability BACE-1 inhibitor; 2-amino-6H-1,3,4-thiadizine; blood-brain barrier permeability
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Shangguan, S.; Wang, F.; Liao, Y.; Yu, H.; Li, J.; Huang, W.; Hu, H.; Yu, L.; Hu, Y.; Sheng, R. Design, Synthesis and Evaluation of 3-(2-Aminoheterocycle)-4-benzyloxyphenylbenzamide Derivatives as BACE-1 Inhibitors. Molecules 2013, 18, 3577-3594.

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