کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1377414 | 981977 | 2007 | 7 صفحه PDF | دانلود رایگان |
Herein is described the design, synthesis, and enzymatic activity of a series of substituted pyrazinones as inhibitors of the TF/VIIa complex. These inhibitors were designed to explore replacement and variation of the P1 amidine described previously [J. Med. Chem.2003, 46, 4050]. The P1 needle replacements were selected based upon their reduced basicity compared to the parent phenyl amidine (pKa ∼ 12). A contributing factor towards the oral bioavailability of a compound is the ionization state of the compound in the intestinal tract. The desired outcome of the study was to identify an orally bioavailable TF–VIIa inhibitor.
The design, synthesis, and biological evaluation of 20 compounds with novel P1 needles is reported. The P1 needle replacements were selected based upon their reduced basicity compared to the parent phenyl amidine (pKa ∼ 12), with the goal of the effort an orally bioavailable TF/VIIa inhibitor.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 17, Issue 16, 15 August 2007, Pages 4568–4574