کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1375989 981948 2005 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
P2 pyridine N-oxide thrombin inhibitors: a novel peptidomimetic scaffold
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
P2 pyridine N-oxide thrombin inhibitors: a novel peptidomimetic scaffold
چکیده انگلیسی

In this study, we have demonstrated that the critical hydrogen bonding motif of the established 3-aminopyrazinone thrombin inhibitors can be effectively mimicked by a 2-aminopyridine N-oxide. As this peptidomimetic core is more resistant toward oxidative metabolism, it also overcomes the metabolic liability associated with the pyrazinones. An optimization study of the P1 benzylamide delivered the potent thrombin inhibitor 21 (Ki = 3.2 nM, 2xaPTT = 360 nM), which exhibited good plasma levels and half-life after oral dosing in the dog (Cmax = 2.6 μM, t1/2 = 4.5 h).

In this study, we demonstrate that the critical hydrogen bonding motif of the established 3-aminopyrazinone thrombin inhibitors can be effectively mimicked by a 2-aminopyridine N-oxide.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 15, Issue 11, 2 June 2005, Pages 2771–2775
نویسندگان
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