Chlorothiophenecarboxamides as P1 surrogates of inhibitors of blood coagulation factor Xa

被引：24

作者：

Mederski, WWKR ^{[1
]}

Cezanne, B

van Amsterdam, C

Bühring, KU

Dorsch, D

Gleitz, J

März, J

Tsaklakidis, C

机构：

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

[2] Inst Pharmacokinet & Metab, D-85567 Grafing, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 23期

关键词：

anticoagulants; factor Xa inhibitors; chlorothiophenecarboxamides; pharmacokinetics; EMD; 495235;

D O I：

10.1016/j.bmcl.2004.09.043

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Neutral chlorothiophenecarboxamides bearing an amino acid and a substituted aniline were synthesized and investigated for their factor Xa inhibitory activity in vitro. From selected 2-methylphenyl morpholinones the solution properties were determined. The most soluble and active compounds were then investigated in different animal species to compare the pharmacokinetic parameters. This led to a potent, water soluble and orally bioavailable candidate for further development: EMD 495235. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：5817 / 5822

页数：6

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