782439-00-3Relevant academic research and scientific papers
Design, synthesis, and biological evaluation of pyrazinones containing novel P1 needles as inhibitors of TF/VIIa
Trujillo, John I.,Huang, Horng-Chih,Neumann, William L.,Mahoney, Matthew W.,Long, Scott,Huang, Wei,Garland, Danny J.,Kusturin, Carrie,Abbas, Zaheer,South, Michael S.,Reitz, David B.
, p. 4568 - 4574 (2008/02/11)
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.
