Potent P2Y₁ urea antagonists bearing various cyclic amine scaffolds

详细信息    查看全文

• 作者：R茅jean Ruel ; Alex ; re L鈥橦eureux ; Carl Thibeault ; Philippe Lapointe ; Alain Martel ; Jennifer X. Qiao ; Ji Hua ; Laura A. Price ; Qimin Wu ; Ming Chang ; Joanna Zheng ; Christine S. Huang ; Ruth R. Wexler ; Robert Rehfuss ; Patrick Y.S. Lam
• 关键词：Purinergic receptors ; P2Y1 antagonists ; Tetrahydroisoquinolines ; Isoindolines ; Piperidines
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：15 December, 2013
• 年：2013
• 卷：23
• 期：24
• 页码：6825-6828
• 全文大小：1002 K

文摘

A number of new amine scaffolds with good inhibitory activity in the ADP-induced platelet aggregation assay have been found to be potent antagonists of the P2Y₁ receptor. SAR optimization led to the identification of isoindoline 3c and piperidine 4a which showed good in vitro binding and functional activities, as well as improved aqueous solubility. Among them, the piperidine 4a showed the best overall profile with favorable PK parameters.