کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1371273 | 981841 | 2012 | 4 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Pyrimidinopyrimidine inhibitors of ketohexokinase: Exploring the ring C2 group that interacts with Asp-27B in the ligand binding pocket
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
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چکیده انگلیسی
Inhibitors of ketohexokinase (KHK) have potential for the treatment of diabetes and obesity. We have continued studies on a pyrimidinopyrimidine series of potent KHK inhibitors by exploring the 2-position substituent (R3) that interacts with Asp-27B in the ATP-binding region of KHK (viz. 1, 2; Table 1). We found that increased spacing between the terminal ammonium group and the heterocyclic scaffold (viz. 16−20), such that interaction with Asp-27B is not possible, still results in potent KHK inhibition (IC50 = 15−50 nM). We propose a new interaction with Asp-194, which serves to expand the pyrimidinopyrimidine pharmacophore.
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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 22, Issue 16, 15 August 2012, Pages 5326–5329
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 22, Issue 16, 15 August 2012, Pages 5326–5329
نویسندگان
Bruce E. Maryanoff, John C. O’Neill, David F. McComsey, Stephen C. Yabut, Diane K. Luci, Alan C. Gibbs, Margery A. Connelly,