کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1372262 | 981867 | 2009 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Second generation of BACE-1 inhibitors part 2: Optimisation of the non-prime side substituent
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
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.
This 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 as PowerPoint slide
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 19, Issue 13, 1 July 2009, Pages 3669–3673
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 19, Issue 13, 1 July 2009, Pages 3669–3673
نویسندگان
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,