کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10593723 | 981813 | 2012 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Aminoimidazoles as BACE-1 inhibitors: The challenge to achieve in vivo brain efficacy
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The evaluation of a series of bicyclic aminoimidazoles as potent BACE-1 inhibitors is described. The crystal structures of compound 14 and compound 23 in complex with BACE-1 reveal hydrogen bond interactions with the protein important for achieving potent inhibition. The optimization of permeability and efflux properties of the compounds are discussed as well as the importance of these properties for attaining in vivo brain efficacy. Compound (R)-25 was selected for evaluation in vivo and 1.5 h after oral administration of 300 μmol/kg and efflux inhibitor GF120918 to wild type mice the brain Aβ40 level was reduced by 17% and the plasma Aβ40 level by 76%.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 22, Issue 5, 1 March 2012, Pages 1854-1859
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 22, Issue 5, 1 March 2012, Pages 1854-1859
نویسندگان
Britt-Marie Swahn, Jörg Holenz, Jacob Kihlström, Karin Kolmodin, Johan Lindström, Niklas Plobeck, Didier Rotticci, Fernando Sehgelmeble, Marie Sundström, Stefan von Berg, Johanna Fälting, Biljana Georgievska, Susanne Gustavsson, Jan Neelissen,