Design and Synthesis of Hydroxyethylene-Based BACE-1 Inhibitors Incorporating Extended P1 Substituents

Novel BACE-1 inhibitors with a hydroxyethylene central core have been developed. Modified P1´ and extended P1 substituents were incorporated with the aim to explore potential interactions with the S1´ and the S1-S3 pocket, respectively, of BACE-1. Inhibitors were identified displaying IC(50) values...

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Detalles Bibliográficos
Autores principales: Sandgren, Veronica, Bäck, Marcus, Kvarnström, Ingemar, Dahlgren, Anders
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bentham Open 2013
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3617544/
https://www.ncbi.nlm.nih.gov/pubmed/23585822
http://dx.doi.org/10.2174/1874104501307010001
Descripción
Sumario:Novel BACE-1 inhibitors with a hydroxyethylene central core have been developed. Modified P1´ and extended P1 substituents were incorporated with the aim to explore potential interactions with the S1´ and the S1-S3 pocket, respectively, of BACE-1. Inhibitors were identified displaying IC(50) values in the nanomolar range, i.e. 69 nM for the most potent compound. Possible inhibitor interactions with the enzyme are also discussed.

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