کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1372168 | 981866 | 2011 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Discovery of cyclic guanidines as potent, orally active, human glucagon receptor antagonists
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موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
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چکیده انگلیسی
In the course of the development of an aminobenzimidazole class of human glucagon receptor (hGCGR) antagonists, a novel class of cyclic guanidine hGCGR antagonists was discovered. Rapid N-dealkylation resulted in poor pharmacokinetic profiles for the benchmark compound in this series. A strategy aimed at blocking oxidative dealkylation led to a series of compounds with improved rodent pharmacokinetic profiles. One compound was orally efficacious in a murine glucagon challenge pharmacodynamic model and also significantly lowered glucose levels in a murine diabetes model.
hGCGR cAMP IC50 = 14 nM. Active at 1 mpk in an ob/ob/hGCGR murine diabetes model.Figure optionsDownload as PowerPoint slide
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 21, Issue 23, 1 December 2011, Pages 7131–7136
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 21, Issue 23, 1 December 2011, Pages 7131–7136
نویسندگان
Christopher Sinz, Jiang Chang, Ashley Rouse Lins, Ed Brady, Mari Candelore, Qing Dallas-Yang, Victor Ding, Guoqiang Jiang, Zhen Lin, Steven Mock, Sajjad Qureshi, Gino Salituro, Richard Saperstein, Jackie Shang, Deborah Szalkowski, Laurie Tota,