Discovery of a Potent and Selective ROMK Inhibitor with Pharmacokinetic Properties Suitable for Preclinical Evaluation

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• 作者：Shawn P. Walsh ; Aurash Shahripour ; Haifeng Tang ; Nardos Teumelsan ; Jessica Frie ; Yuping Zhu ; Birgit T. Priest ; Andrew M. Swensen ; Jessica Liu ; Michael Margulis ; Richard Visconti ; Adam Weinglass ; John P. Felix ; Richard M. Brochu ; Timothy Bailey ; Brande Thomas-Fowlkes ; Magdalena Alonso-Galicia ; Xiaoyan Zhou ; Lee-Yuh Pai ; Aaron Corona ; Caryn Hampton ; Melba Hernandez ; Ross Bentley ; Jing Chen ; Kashmira Shah ; Joseph Metzger ; Michael Forrest ; Karen Owens ; Vincent Tong ; Sookhee Ha ; Sophie Roy ; Gregory J. Kaczorowski ; Lihu Yang ; Emma Parmee ; Maria L. Garcia ; Kathleen Sullivan ; Alexander Pasternak
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2015
• 出版时间：July 9, 2015
• 年：2015
• 卷：6
• 期：7
• 页码：747-752
• 全文大小：335K
• ISSN：1948-5875

文摘

A new subseries of ROMK inhibitors exemplified by 28 has been developed from the initial screening hit 1. The excellent selectivity for ROMK inhibition over related ion channels and pharmacokinetic properties across preclinical species support further preclinical evaluation of 28 as a new mechanism diuretic. Robust pharmacodynamic effects in both SD rats and dogs have been demonstrated.