Chackalamannil Samuel, Wang Yuguang, Greenlee William J, Hu Zhiyong, Xia Yan, Ahn Ho-Sam, Boykow George, Hsieh Yunsheng, Palamanda Jairam, Agans-Fantuzzi Jacqueline, Kurowski Stan, Graziano Michael, Chintala Madhu
Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
J Med Chem. 2008 Jun 12;51(11):3061-4. doi: 10.1021/jm800180e. Epub 2008 May 1.
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.
本文描述了基于天然产物himbacine发现的一系列具有极强活性的凝血酶受体（PAR-1）拮抗剂。对该系列化合物的优化已导致发现了化合物4（SCH 530348），这是一种强效口服抗血小板药物，目前正处于针对急性冠状动脉综合征（不稳定型心绞痛/非ST段抬高型心肌梗死）和高危患者心血管事件二级预防的III期临床试验阶段。
