Discovery of a Novel, Orally Active Himbacine-Based Thrombin Receptor Antagonist (SCH 530348) with Potent Antiplatelet Activity
Journal of Medicinal Chemistry2008Vol. 51(11), pp. 3061–3064
Citations Over TimeTop 10% of 2008 papers
Samuel Chackalamannil, Yuguang Wang, William J. Greenlee, Zhiyong Hu, Yan Xia, Ho-Sam Ahn, George Boykow, Yunsheng Hsieh, Jairam Palamanda, Jacqueline Agans-Fantuzzi, Stan Kurowski, Michael P. Graziano, Madhu Chintala
Abstract
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.
Related Papers
- → Thrombin-induced events in non-platelet cells are mediated by the unique proteolytic mechanism established for the cloned platelet thrombin receptor.(1992)148 cited
- → Thrombin Activates NF‐κB through Thrombin Receptor and Results in Proliferation of Vascular Smooth Muscle Cells: Role of Thrombin in Atherosclerosis and Restenosis(1997)57 cited
- → Surface thrombomodulin modulates thrombin receptor responses on vascular smooth muscle cells(1996)38 cited
- → "Mirror image" antagonists of thrombin-induced platelet activation based on thrombin receptor structure.(1992)53 cited
- → Multiple pathways of thrombin-induced platelet activation differentiated by desensitization and a thrombin exosite inhibitor(1991)37 cited