Nonbenzamidine tetrazole derivatives as factor Xa inhibitors

被引：33

作者：

Quan, ML ^{[1
]}

Ellis, CD ^{[1
]}

He, MY ^{[1
]}

Liauw, AY ^{[1
]}

Woerner, FJ ^{[1
]}

Alexander, RS ^{[1
]}

Knabb, RM ^{[1
]}

Lam, PYS ^{[1
]}

Luettgen, JM ^{[1
]}

Wong, PC ^{[1
]}

Wright, MR ^{[1
]}

Wexler, RR ^{[1
]}

机构：

[1] Bristol Myers Squibb Co, Wilmington, DE 19880 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 03期

关键词：

D O I：

10.1016/S0960-894X(02)00951-4

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Factor Xa (fXa) is an important serine protease that holds the central position linking the intrinsic and extrinsic activation mechanisms in the blood coagulation cascade. Therefore, inhibition of fXa has potential therapeutic applications in the treatments of both arterial and venous thrombosis. Herein we describe a series of tetrazole fXa inhibitors containing benzamidine mimics as the P, substrate, of which the aminobenzisoxazole moiety was found to be the most potent benzamidine mimic. SR374 (12) inhibits fXa with a K-i value of 0.35 nM and is very selective for fXa over thrombin and trypsin. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：369 / 373

页数：5

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