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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Detalles Bibliográficos
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
Descripción
Sumario: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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