Halothiophene benzimidazoles as P1 surrogates of inhibitors of blood coagulation factor Xa

被引：78

作者：

Mederski, WWKR ^{[1
]}

Dorsch, D ^{[1
]}

Anzali, S ^{[1
]}

Gleitz, J ^{[1
]}

Cezanne, B ^{[1
]}

Tsaklakidis, C ^{[1
]}

机构：

[1] Merck KGaA, Preclin Pharmaceut Res, D-64271 Darmstadt, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 14期

关键词：

anti-coagulants; factor Xa inhibitors; halothiophene benzimidazoles; x-ray crystal structures;

D O I：

10.1016/j.bmcl.2004.04.097

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Neutral weak halothiophene benzimidazole inhibitors of the serine protease factor Xa were identified via screening of a compound library. The X-ray crystal structure of representative 3a bound to human fXa confirmed the S1 binding mode. Starting from 3a a series of halothiophene benzimidazoles was synthesized and investigated for their factor Xa inhibitory activity. This led to potent and selective achiral inhibitors against fXa such as compounds 9k and 9w. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：3763 / 3769

页数：7