| Literature DB >> 19406640 |
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
Our first generation of hydroxyethylamine BACE-1 inhibitors proved unlikely to provide molecules that would lower amyloid in an animal model at low oral doses. This observation led us to the discovery of a second generation of inhibitors having nanomolar activity in a cell-based assay and with the potential for improved pharmacokinetic profiles. In this Letter, we describe our successful strategy for the optimization of oral bioavailability and also give insights into the design of compounds with the potential for improved brain penetration.Entities:
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Year: 2009 PMID： 19406640 DOI： 10.1016/j.bmcl.2009.03.149
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823