183307-56-4Relevant articles and documents
Design, synthesis, and activity of 2,6-diphenoxypyridine-derived factor Xa inhibitors
Phillips, Gary,Davey, David D.,Eagen, Keith A.,Koovakkat, Sunil K.,Liang, Amy,Ng, Howard P.,Pinkerton, Michael,Trinh, Lan,Whitlow, Marc,Beatty, Alicia M.,Morrissey, Michael M.
, p. 1749 - 1756 (1999)
A novel series of 2,6-diphenoxypyridines has been designed to inhibit factor Xa, a serine protease strategically located in the coagulation cascade. The evolution from the photochemically unstable bisamidine (Z,Z)- BABCH to potent bisamidine compounds with a pyridine heterocycle as the core scaffold has been achieved. The most potent compound in the series, 6h, has a K(i) for human factor Xa of 12 nM. The selectivity of 6h against bovine trypsin and human thrombin was greater than 90- and 1000-fold, respectively. Two proposed modes of binding of 6h to factor Xa are made based on the crystal structures of 6h by itself and of 6h bound to bovine trypsin.
