Design, synthesis, and biological evaluation of pyrazinones containing novel P1 needles as inhibitors of TF/VIIa

…, WL Neumann, MW Mahoney, S Long, W Huang…

Index: 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. Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 16 p. 4568 - 4574

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Citation Number: 19

Abstract

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 ...