| Literature DB >> 19477642 |
Nicolas Charrier1, 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, Kathrine J Smith, Sharon Sweitzer, Pam Theobald, David Vesey, Daryl S Walter, Gareth Wayne.
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.Entities:
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Year: 2009 PMID： 19477642 DOI： 10.1016/j.bmcl.2009.03.150
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823