Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1369896 | Bioorganic & Medicinal Chemistry Letters | 2014 | 5 Pages |
Abstract
Spiropiperidine indoline-substituted diaryl ureas had been identified as antagonists of the P2Y1 receptor. Enhancements in potency were realized through the introduction of a 7-hydroxyl substitution on the spiropiperidinylindoline chemotype. SAR studies were conducted to improve PK and potency, resulting in the identification of compound 3e, a potent, orally bioavailable P2Y1 antagonist with a suitable PK profile in preclinical species. Compound 3e demonstrated a robust antithrombotic effect in vivo and improved bleeding risk profile compared to the P2Y12 antagonist clopidogrel in rat efficacy/bleeding models.
Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide
Keywords
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Yoon T. Jeon, Wu Yang, Jennifer X. Qiao, Ling Li, Rejean Ruel, Carl Thibeault, Sheldon Hiebert, Tammy C. Wang, Yufeng Wang, Yajun Liu, Charles G. Clark, Henry S. Wong, Juliang Zhu, Dauh-Rurng Wu, Dawn Sun, Bang-Chi Chen, Arvind Mathur, Silvi A. Chacko,