Author/Authors :
Jennifer R. Riggs، نويسنده , , Aleksandr Kolesnikov، نويسنده , , John Hendrix Hinshaw، نويسنده , , Wendy B. Young، نويسنده , , William D. Shrader، نويسنده , , Dange Vijaykumar، نويسنده , , Robin Stephens، نويسنده , , Liang Liu، نويسنده , , Lin Pan، نويسنده , , Joyce Mordenti، نويسنده , , Michael J. Green، نويسنده , , Juthamas Sukbuntherng، نويسنده ,
Abstract :
We have developed a series of potent and selective factor VIIa inhibitors based on the 2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6-hydroxy-biphenyl-3-yl]-succinic acid scaffold. These amidine-containing compounds have low oral bioavailability. Herein, we describe our efforts to improve the oral bioavailability of the parent amidine via a prodrug strategy where the amidine basicity and polarity were reduced with either an alkoxy-amidine or a carbamate prodrug.
Keywords :
Factor VIIa , Anticoagulants , thrombosis , prodrug , Amidine , Amidoxime , Hydroxy amidine , Serine protease , Carbamate prodrugs , Pharmacokinetics , indole synthesis , Alkoxy amidine
