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
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author Sandgren, Veronica
Bäck, Marcus
Kvarnström, Ingemar
Dahlgren, Anders
author_facet Sandgren, Veronica
Bäck, Marcus
Kvarnström, Ingemar
Dahlgren, Anders
author_sort Sandgren, Veronica
collection PubMed
description 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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spelling pubmed-36175442013-04-12 Design and Synthesis of Hydroxyethylene-Based BACE-1 Inhibitors Incorporating Extended P1 Substituents Sandgren, Veronica Bäck, Marcus Kvarnström, Ingemar Dahlgren, Anders Open Med Chem J Article 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. Bentham Open 2013-03-08 /pmc/articles/PMC3617544/ /pubmed/23585822 http://dx.doi.org/10.2174/1874104501307010001 Text en © Sandgren et al.; Licensee Bentham Open. http: //creativecommons.org/licenses/by/2.5/ This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http: //creativecommons.org/licenses/by/2.5/), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
spellingShingle Article
Sandgren, Veronica
Bäck, Marcus
Kvarnström, Ingemar
Dahlgren, Anders
Design and Synthesis of Hydroxyethylene-Based BACE-1 Inhibitors Incorporating Extended P1 Substituents
title Design and Synthesis of Hydroxyethylene-Based BACE-1 Inhibitors Incorporating Extended P1 Substituents
title_full Design and Synthesis of Hydroxyethylene-Based BACE-1 Inhibitors Incorporating Extended P1 Substituents
title_fullStr Design and Synthesis of Hydroxyethylene-Based BACE-1 Inhibitors Incorporating Extended P1 Substituents
title_full_unstemmed Design and Synthesis of Hydroxyethylene-Based BACE-1 Inhibitors Incorporating Extended P1 Substituents
title_short Design and Synthesis of Hydroxyethylene-Based BACE-1 Inhibitors Incorporating Extended P1 Substituents
title_sort design and synthesis of hydroxyethylene-based bace-1 inhibitors incorporating extended p1 substituents
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3617544/
https://www.ncbi.nlm.nih.gov/pubmed/23585822
http://dx.doi.org/10.2174/1874104501307010001
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