Selective and dual action orally active inhibitors of thrombin and factor Xa

被引：19
|
作者：
Young, Robert J.
Brown, David
Burns-Kurtis, Cynthia L.
Chan, Chuen
Convery, Maire A.
Hubbard, Julia A.
Kelly, Henry A.
Pateman, Anthony J.
Patikis, Angela
Senger, Stefan
Shah, Gita P.
Toomey, John R.
Watson, Nigel S.
Zhou, Ping
机构：
[1] GlaxoSmithKline, Med Res Ctr, Stevenage SG1 2NY, Herts, England
[2] GlaxoSmithKline, King Of Prussia, PA 19406 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 10期
关键词：
factor Xa; thrombin; oral; dual inhibitor;
D O I：
10.1016/j.bmcl.2007.03.080
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
The synthetic entry to new classes of dual fXa/thrombin and selective thrombin inhibitors with significant oral bioavailability is described. This was achieved through minor modifications to the sulfonamide group in our potent and selective fxa inhibitor (E)-2-(5-chlorothien-2-yl)-N-{(3S)-1-[(1S)-1-methyl-2-(morpholin-4-yl)-2-oxoethyl]-2-oxopyrrolidin-3-yl} ethenesulfonamide and these observed activity changes have been rationalised using structural studies. (c) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码：2927 / 2930
页数：4
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