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