Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1372262 | Bioorganic & Medicinal Chemistry Letters | 2009 | 5 Pages |
Abstract
Our first generation of hydroxyethylamine transition-state mimetic BACE-1 inhibitors allowed us to validate BACE-1 as a key target for Alzheimer’s disease by demonstrating amyloid lowering in an animal model, albeit at rather high doses. Finding a molecule from this series which was active at lower oral doses proved elusive and demonstrated the need to find a novel series of inhibitors with improved pharmacokinetics. This Letter describes the discovery of such inhibitors.
Graphical abstractThis article discloses the strategy that led to the discovery of a second series of hydroxyethylamine BACE-1 inhibitors with non-prime side substituents of higher binding efficiency.Figure optionsDownload full-size imageDownload as PowerPoint slide
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Nicolas Charrier, Brian Clarke, Emmanuel Demont, Colin Dingwall, Rachel Dunsdon, Julie Hawkins, Julia Hubbard, Ishrut Hussain, Graham Maile, Rosalie Matico, Julie Mosley, Alan Naylor, Alistair O’Brien, Sally Redshaw, Paul Rowland, Virginie Soleil,