کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1379074 | 982017 | 2006 | 5 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Factor VIIa inhibitors: Gaining selectivity within the trypsin family Factor VIIa inhibitors: Gaining selectivity within the trypsin family](/preview/png/1379074.png)
Within the trypsin family of coagulation proteases, obtaining highly selective inhibitors of factor VIIa has been challenging. We report a series of factor VIIa (fVIIa) inhibitors based on the 5-amidino-2-(2-hydroxy-biphenyl-3-yl)-benzimidazole (1) scaffold with potency for fVIIa and high selectivity against factors IIa, Xa, and trypsin. With this scaffold class, we propose that a unique hydrogen bond interaction between a hydroxyl on the distal ring of the biaryl system and the backbone carbonyl of fVIIa lysine-192 provides a basis for enhanced selectivity and potency for fVIIa.
A series of highly selective and potent factor VIIa-tissue factor (fVIIa/TF) complex inhibitors were generated via a Suzuki-based synthesis strategy. With this scaffold class (9), we propose that a unique hydrogen bond interaction between a hydroxyl on the biaryl system and the backbone carbonyl of fVIIa Lys-192 provides a basis for enhanced selectivity and potency.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 16, Issue 6, 15 March 2006, Pages 1596–1600