Design, synthesis, and in vitro biological activity of benzimidazole basedfactor Xa inhibitors

Authors
Zhao, ZS Arnaiz, DO Griedel, B Sakata, S Dallas, JL Whitlow, M Trinh, L Post, J Liang, A Morrissey, MM Shaw, KJ
Citation
Zs. Zhao et al., Design, synthesis, and in vitro biological activity of benzimidazole basedfactor Xa inhibitors, BIOORG MED, 10(9), 2000, pp. 963-966
Citations number
11
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
10
Issue
9
Year of publication
2000
Pages
963 - 966
Database
ISI
SICI code
0960-894X(20000501)10:9<963:DSAIVB>2.0.ZU;2-0
Abstract
Inhibitors based on the benzimidazole scaffold showed subnanomolar potency against Factor Xa with 500-1000-fold selectivity against thrombin and 50-10 0-fold selectivity against trypsin. The 2-substituent on the benzimidazole ring had a strong impact on the FXa inhibitory activity. Crystallography st udies suggest that the 2-substituent may have a conformational effect favor ing the extended binding conformation. (C) 2000 Elsevier Science Ltd. All r ights reserved.