کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1377335 | 981976 | 2008 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
BACE-1 inhibitors part 3: Identification of hydroxy ethylamines (HEAs) with nanomolar potency in cells
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موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
This article is focusing on further optimization of previously described hydroxy ethylamine (HEA) BACE-1 inhibitors obtained from a focused library with the support of X-ray crystallography. Optimization of the non-prime side of our inhibitors and introduction of a 6-membered sultam substituent binding to Asn-294 as well as a fluorine in the C-2 position led to derivatives with nanomolar potency in cell-based assays.
Modifications to the non-prime side of a series of BACE-1 inhibitors are presented. This final round of optimisation led to inhibitors with nanomolar potency in a cell-based assay which were capable of lowering amyloid production in an animal model following oral administration.Figure optionsDownload as PowerPoint slide
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 18, Issue 3, 1 February 2008, Pages 1022–1026
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 18, Issue 3, 1 February 2008, Pages 1022–1026
نویسندگان
Paul Beswick, Nicolas Charrier, Brian Clarke, Emmanuel Demont, Colin Dingwall, Rachel Dunsdon, Andrew Faller, Robert Gleave, Julie Hawkins, Ishrut Hussain, Christopher N. Johnson, David MacPherson, Graham Maile, Rosalie Matico, Peter Milner,