کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10594089 | 981818 | 2011 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Discovery and hit-to-lead optimization of novel allosteric glucokinase activators
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
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چکیده انگلیسی
We report on a hit generation and hit-to-lead program of a novel class of glucokinase activators (GKAs). Hit compounds, activators at low glucose concentration only were identified by vHTS. Scaffold modification reliably afforded activators also at high substrate level. Potency was increased by introduction of a hydrogen bond acceptor as proposed by molecular docking. Replacement of the initial alkylene linkers with a rigid 1,2-phenylene motif followed by further studies eventually furnished a series of potent lead compounds exhibiting steep SAR.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 21, Issue 18, 15 September 2011, Pages 5417-5422
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 21, Issue 18, 15 September 2011, Pages 5417-5422
نویسندگان
Martin Lang, Markus H.-J. Seifert, Kristina K. Wolf, Andrea Aschenbrenner, Roland Baumgartner, Tanja Wieber, Viola Trentinaglia, Marcus Blisse, Nobumitsu Tajima, Tokuyuki Yamashita, Daniel Vitt, Hitoshi Noda,