کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1375989 | 981948 | 2005 | 5 صفحه PDF | دانلود رایگان |

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
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 15, Issue 11, 2 June 2005, Pages 2771–2775