Design and Synthesis of Hydroxyethylene-Based BACE-1 Inhibitors Incorporating Extended P1 Substituents
Veronica Sandgren*, Marcus Bäck, Ingemar Kvarnström , Anders Dahlgren
Identifiers and Pagination:Year: 2013
First Page: 1
Last Page: 15
Publisher Id: TOMCJ-7-1
Article History:Received Date: 14/8/2012
Revision Received Date: 18/11/2012
Acceptance Date: 26/11/2012
Electronic publication date: 8/3/2013
Collection year: 2013
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.
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 IC50 values in the nanomolar range, i.e. 69 nM for the most potent compound. Possible inhibitor interactions with the enzyme are also discussed.