Bioorganic & Medicinal Chemistry Letters 2000-05-01

Design, synthesis, and in vitro biological activity of benzimidazole based factor Xa inhibitors.

Z Zhao, D O Arnaiz, B Griedel, S Sakata, J L Dallas, M Whitlow, L Trinh, J Post, A Liang, M M Morrissey, K J Shaw

Index: Bioorg. Med. Chem. Lett. 10(9) , 963-6, (2000)

Full Text: HTML

Abstract

Inhibitors based on the benzimidazole scaffold showed subnanomolar potency against Factor Xa with 500-1000-fold selectivity against thrombin and 50-100-fold selectivity against trypsin. The 2-substituent on the benzimidazole ring had a strong impact on the FXa inhibitory activity. Crystallography studies suggest that the 2-substituent may have a conformational effect favoring the extended binding conformation.