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
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Discovery and hit-to-lead optimization of novel allosteric glucokinase activators
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
نویسندگان
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