Factor VIIa inhibitors: chemical optimization, preclinical pharmacokinetics, pharmacodynamics, and efficacy in an arterial baboon thrombosis model

…, S Torkelson, WD Shrader, A Kolesnikov, R Rai…

Index: Young, Wendy B.; Mordenti, Joyce; Torkelson, Steven; Shrader, William D.; Kolesnikov, Aleksandr; Rai, Roopa; Liu, Liang; Hu, Huiyong; Leahy, Ellen M.; Green, Michael J.; Sprengeler, Paul A.; Katz, Bradley A.; Yu, Christine; Janc, James W.; Elrod, Kyle C.; Marzec, Ulla M.; Hanson, Stephen R. Bioorganic and Medicinal Chemistry Letters, 2006 , vol. 16, # 7 p. 2037 - 2041

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Citation Number: 31

Abstract

Highly selective and potent factor VIIa–tissue factor (fVIIa· TF) complex inhibitors were generated through structure-based design. The pharmacokinetic properties of an optimized analog (9) were characterized in several preclinical species, demonstrating pharmacokinetic characteristics suitable for once-a-day dosing in humans. Analog 9 inhibited platelet and fibrin deposition in a dose-dependent manner after intravenous administration in a ...

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