Next Article in Journal
Synthesis and Characterization of Celecoxib Derivatives as Possible Anti-Inflammatory, Analgesic, Antioxidant, Anticancer and Anti-HCV Agents
Previous Article in Journal
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,*
1 ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China 2 The National Center for Drug Screening, Shanghai 201203, China 3 Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China 4 Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
* Author to whom correspondence should be addressed.
Received: 17 February 2013 / Revised: 15 March 2013 / Accepted: 18 March 2013 / Published: 20 March 2013
(This article belongs to the Section Medicinal Chemistry)
Download PDF [433 KB, uploaded 18 June 2014]

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.

Share & Cite This Article

Export to BibTeX |
EndNote


MDPI and ACS Style

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.

View more citation formats

Related Articles

Article Metrics

Comments

Citing Articles

[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert