Orally efficacious thrombin inhibitors with cyanofluorophenylacetamide as the P2 motif

被引：29

作者：

Kreutter, Kevin D. ^{[1
]}

Lu, Tianbao ^{[1
]}

Lee, Lily ^{[1
]}

Giardino, Edward C. ^{[1
]}

Patel, Sharmila ^{[1
]}

Huang, Hui ^{[1
]}

Xu, Guozhang ^{[1
]}

Fitzgerald, Mark ^{[1
]}

Haertlein, Barbara J. ^{[1
]}

Mohan, Venkatraman ^{[1
]}

Crysler, Carl ^{[1
]}

Eisennagel, Stephen ^{[1
]}

Dasgupta, Malini ^{[1
]}

McMillan, Martin ^{[1
]}

Spurlino, John C. ^{[1
]}

Huebert, Norman D. ^{[1
]}

Maryanoff, Bruce E. ^{[1
]}

Tomczuk, Bruce E. ^{[1
]}

Damiano, Bruce P. ^{[1
]}

Player, Mark R. ^{[1
]}

机构：

[1] Johnson & Johnson Pharmaceut Res & Dev, Spring House, PA 19477 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 09期

关键词：

thrombin inhibitor; trypsin; serine protease; anticoagulant;

D O I：

10.1016/j.bmcl.2008.03.087

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

2-Cyano-6-fluorophenylacetamide was explored as a novel P2 scaffold in the design of thrombin inhibitors. Optimization around this structural motif culminated in 14, which is a potent thrombin inhibitor (K-i = 1.2 nM) that exhibits robust efficacy in canine anticoagulation and thrombosis models upon oral administration. (c) 2008 Elsevier Ltd. All rights reserved.

引用

页码：2865 / 2870

页数：6

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