Discovery of a novel, orally active himbacine-based thrombin receptor antagonist (SCH 530348) with potent antiplatelet activity

被引：233

作者：

Chackalamannil, Samuel ^{[1
]}

Wang, Yuguang ^{[1
]}

Greenlee, William J. ^{[1
]}

Hu, Zhiyong ^{[1
]}

Xia, Yan ^{[1
]}

Ahn, Ho-Sam ^{[1
]}

Boykow, George ^{[1
]}

Hsieh, Yunsheng ^{[1
]}

Palamanda, Jairam ^{[1
]}

Agans-Fantuzzi, Jacqueline ^{[1
]}

Kurowski, Stan ^{[1
]}

Graziano, Michael ^{[1
]}

Chintala, Madhu ^{[1
]}

机构：

[1] Schering Plough Res Inst, Kenilworth, NJ 07033 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 11期

关键词：

D O I：

10.1021/jm800180e

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The discovery of an exceptionally potent series of thrombin receptor (PAR-1) antagonists based on the natural product himbacine is described. Optimization of this series has led to the discovery of 4 (SCH 530348), a potent, oral antiplatelet agent that is currently undergoing Phase-III clinical trials for acute coronary syndrome (unstable angina/non-ST segment elevation myocardial infarction) and secondary prevention of cardiovascular events in high-risk patients.

引用

页码：3061 / 3064

页数：4

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