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Discovery of a Novel, Orally Active Himbacine-Based Thrombin Receptor Antagonist (SCH 530348) with Potent Antiplatelet Activity

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Schering-Plough Research Institute, 2015 Galloping Hill Rd, Kenilworth, New Jersey 07033
* To whom correspondence should be addressed. Phone: 908-740-3474 . Fax: 908-740-7164. E-mail: [email protected]
Cite this: J. Med. Chem. 2008, 51, 11, 3061–3064
Publication Date (Web):May 1, 2008
https://doi.org/10.1021/jm800180e
Copyright © 2008 American Chemical Society

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    Abstract

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    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.

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    Experimental procedures for platelet aggregation studies, PAR-1 binding assay, and synthesis and characterization of intermediates and selected final products. This material is available free of charge via Internet at http://pubs.acs.org.

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