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

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...

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Autores principales: Shangguan, Shihao, Wang, Fei, Liao, Yong, Yu, Haiping, Li, Jia, Huang, Wenhai, Hu, Haihong, Yu, Lushan, Hu, Yongzhou, Sheng, Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269915/
https://www.ncbi.nlm.nih.gov/pubmed/23519200
http://dx.doi.org/10.3390/molecules18033577
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author Shangguan, Shihao
Wang, Fei
Liao, Yong
Yu, Haiping
Li, Jia
Huang, Wenhai
Hu, Haihong
Yu, Lushan
Hu, Yongzhou
Sheng, Rong
author_facet Shangguan, Shihao
Wang, Fei
Liao, Yong
Yu, Haiping
Li, Jia
Huang, Wenhai
Hu, Haihong
Yu, Lushan
Hu, Yongzhou
Sheng, Rong
author_sort Shangguan, Shihao
collection PubMed
description 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 IC(50) 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.
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spelling pubmed-62699152018-12-20 Design, Synthesis and Evaluation of 3-(2-Aminoheterocycle)-4-benzyloxyphenylbenzamide Derivatives as BACE-1 Inhibitors Shangguan, Shihao Wang, Fei Liao, Yong Yu, Haiping Li, Jia Huang, Wenhai Hu, Haihong Yu, Lushan Hu, Yongzhou Sheng, Rong Molecules Article 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 IC(50) 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. MDPI 2013-03-20 /pmc/articles/PMC6269915/ /pubmed/23519200 http://dx.doi.org/10.3390/molecules18033577 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Shangguan, Shihao
Wang, Fei
Liao, Yong
Yu, Haiping
Li, Jia
Huang, Wenhai
Hu, Haihong
Yu, Lushan
Hu, Yongzhou
Sheng, Rong
Design, Synthesis and Evaluation of 3-(2-Aminoheterocycle)-4-benzyloxyphenylbenzamide Derivatives as BACE-1 Inhibitors
title Design, Synthesis and Evaluation of 3-(2-Aminoheterocycle)-4-benzyloxyphenylbenzamide Derivatives as BACE-1 Inhibitors
title_full Design, Synthesis and Evaluation of 3-(2-Aminoheterocycle)-4-benzyloxyphenylbenzamide Derivatives as BACE-1 Inhibitors
title_fullStr Design, Synthesis and Evaluation of 3-(2-Aminoheterocycle)-4-benzyloxyphenylbenzamide Derivatives as BACE-1 Inhibitors
title_full_unstemmed Design, Synthesis and Evaluation of 3-(2-Aminoheterocycle)-4-benzyloxyphenylbenzamide Derivatives as BACE-1 Inhibitors
title_short Design, Synthesis and Evaluation of 3-(2-Aminoheterocycle)-4-benzyloxyphenylbenzamide Derivatives as BACE-1 Inhibitors
title_sort design, synthesis and evaluation of 3-(2-aminoheterocycle)-4-benzyloxyphenylbenzamide derivatives as bace-1 inhibitors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269915/
https://www.ncbi.nlm.nih.gov/pubmed/23519200
http://dx.doi.org/10.3390/molecules18033577
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