Amido-(propyl and allyl)-hydroxybenzamidines: Development of achiral inhibitors of factor Xa

Authors
Gong, Y Pauls, HW Spada, AP Czekaj, M Liang, GY Chu, V Colussi, DJ Brown, KD Gao, JB
Citation
Y. Gong et al., Amido-(propyl and allyl)-hydroxybenzamidines: Development of achiral inhibitors of factor Xa, BIOORG MED, 10(3), 2000, pp. 217-221
Citations number
29
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
10
Issue
3
Year of publication
2000
Pages
217 - 221
Database
ISI
SICI code
0960-894X(20000207)10:3<217:AAADOA>2.0.ZU;2-N
Abstract
The design, synthesis and SAR of amido-(propyl and allyl)-hydroxybenzamidin e coagulation factor Xa inhibitors is described. These achiral inhibitors a re selective for fXa vis a vis structurally related serine proteases and ar e readily prepared in 6-7 linear steps. The most potent member 9j (fXa K-i = 0.75 nM) is selective (>1000-fold) and an effective anticoagulant in mamm alian plasma. (C) 2000 Elsevier Science Ltd. All rights reserved.