| Literature DB >> 19428244 |
Nicolas Charrier1, Brian Clarke, Leanne Cutler, Emmanuel Demont, Colin Dingwall, Rachel Dunsdon, Julie Hawkins, Colin Howes, 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
Inhibition of the aspartyl protease BACE-1 has the potential to deliver a disease-modifying therapy for Alzheimer's disease. We have recently disclosed a series of transition-state mimetic BACE-1 inhibitors showing nanomolar potency in cell-based assays. Amongst them, GSK188909 (compound 2) had favorable pharmacokinetics and was the first orally bioavailable inhibitor reported to demonstrate brain amyloid lowering in an animal model. In this Letter, we describe the reasons that led us to favor a second generation of inhibitors for further in vivo studies.Entities:
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Year: 2009 PMID： 19428244 DOI： 10.1016/j.bmcl.2009.03.165
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823