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Design and Synthesis of Hydroxyethylene-Based BACE-1 Inhibitors Incorporating Extended P1 Substituents
The Open Medicinal Chemistry Journal
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8 Mar 2013 •
RESEARCH ARTICLE
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DOI: 10.2174/1874104501307010001
Abstract
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.
Keywords: Alzheimer’s disease, BACE-1 inhibitors, extended P1 substituents, hydroxyethylene isosteres, P1´ modifications, S1-S3 pocket.
