Optimization of the β-aminoester class of factor Xa inhibitors.: Part 2:: Identification of FXV673 as a potent and selective inhibitor with excellent in vivo anticoagulant activity

被引：50

作者：

Guertin, KR ^{[1
]}

Gardner, CJ ^{[1
]}

Klein, SI ^{[1
]}

Zulli, AL ^{[1
]}

Czekaj, M ^{[1
]}

Gong, Y ^{[1
]}

Spada, AP ^{[1
]}

Cheney, DL ^{[1
]}

Maignan, S ^{[1
]}

Guilloteau, JP ^{[1
]}

Brown, KD ^{[1
]}

Colussi, DJ ^{[1
]}

Chu, V ^{[1
]}

Heran, CL ^{[1
]}

Morgan, SR ^{[1
]}

Bentley, RG ^{[1
]}

Dunwiddie, CT ^{[1
]}

Leadley, RJ ^{[1
]}

Pauls, HW ^{[1
]}

机构：

[1] Aventis Pharmaceut, Drug Innovat & Approval, Bridgewater, NJ 08807 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 12期

关键词：

D O I：

10.1016/S0960-894X(02)00213-5

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Further optimization of the beta-aminoester class of factor Xa (fXa) inhibitors is described culminating in the identification of 9c (FXV673), a potent and selective factor Xa inhibitor with excellent in vivo anticoagulant activity. An X-ray structure of FXV673 bound to human fXa is also presented. Based on its selectivity, potent in vivo activity and favorable pre-clinical safety profile, FXV673 was selected for further development and is currently undergoing clinical trials. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：1671 / 1674

页数：4

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