Chelliah Mariappan V, Chackalamannil Samuel, Xia Yan, Eagen Keith, Clasby Martin C, Gao Xiaobang, Greenlee William, Ahn Ho-Sam, Agans-Fantuzzi Jacqueline, Boykow George, Hsieh Yunsheng, Bryant Matthew, Palamanda Jairam, Chan Tze-Ming, Hesk David, Chintala Madhu
Central Nervous System and Cardiovascular Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA.
J Med Chem. 2007 Oct 18;50(21):5147-60. doi: 10.1021/jm070704k. Epub 2007 Sep 14.
Pursuing our earlier efforts in the himbacine-based thrombin receptor antagonist area, we have synthesized a series of compounds that incorporate heteroatoms in the C-ring of the tricyclic motif. This effort has resulted in the identification of several potent heterocyclic analogs with excellent affinity for the thrombin receptor. Several of these compounds demonstrated robust inhibition of platelet aggregation in an ex vivo model in cynomolgus monkeys following oral administration. A detailed profile of 28b, a benchmark compound in this series, with a Ki of 4.3 nM, is presented.
在基于辛巴生的凝血酶受体拮抗剂领域继续我们早期的研究工作，我们合成了一系列在三环基序的C环中引入杂原子的化合物。这项工作已鉴定出几种对凝血酶受体具有优异亲和力的强效杂环类似物。其中几种化合物在食蟹猴的离体模型中口服给药后显示出对血小板聚集的强效抑制作用。本文介绍了该系列中的基准化合物28b的详细概况，其Ki为4.3 nM。
