Discovery of 2-(phenoxypyridine)-3-phenylureas as small molecule P2Y1 antagonists

H Chao, H Turdi, TF Herpin, JY Roberge…

Index: Chao, Hannguang; Turdi, Huji; Herpin, Timothy F.; Roberge, Jacques Y.; Liu, Yalei; Schnur, Dora M.; Poss, Michael A.; Rehfuss, Robert; Hua, Ji; Wu, Qimin; Price, Laura A.; Abell, Lynn M.; Schumacher, William A.; Bostwick, Jeffrey S.; Steinbacher, Thomas E.; Stewart, Anne B.; Ogletree, Martin L.; Huang, Christine S.; Chang, Ming; Cacace, Angela M.; Arcuri, Maredith J.; Celani, Deborah; Wexler, Ruth R.; Lawrence, R. Michael Journal of Medicinal Chemistry, 2013 , vol. 56, # 4 p. 1704 - 1714

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Citation Number: 21

Abstract

Two distinct G protein-coupled purinergic receptors, P2Y1 and P2Y12, mediate ADP-driven platelet activation. The clinical effectiveness of P2Y12 blockade is well established. Recent preclinical data suggest that P2Y1 and P2Y12 inhibition provide equivalent antithrombotic efficacy, while targeting P2Y1 has the potential for reduced bleeding liability. In this account, the discovery of a 2-(phenoxypyridine)-3-phenylurea chemotype that inhibited ADP- ...