title: Design and Synthesis of Hydroxyethylene-Based BACE-1 Inhibitors Incorporating Extended P1 Substituents.
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.
authors.affiliation: Department of Chemistry, Linköping University, S-581 83 Linköping, Sweden.
authors.forename: Veronica
authors.initials: V
authors.lastname: Sandgren
authors.forename: Marcus
authors.initials: M
authors.lastname: Bäck
authors.forename: Ingemar
authors.initials: I
authors.lastname: Kvarnström
authors.forename: Anders
authors.initials: A
authors.lastname: Dahlgren
keywords: Alzheimer’s disease; BACE-1 inhibitors; P1´ modifications; S1-S3 pocket.; extended P1 substituents; hydroxyethylene isosteres