Channelpedia

PubMed 24075732


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kir1.1 , Kv11.1



Title: Discovery of a novel sub-class of ROMK channel inhibitors typified by 5-(2-(4-(2-(4-(1H-Tetrazol-1-yl)phenyl)acetyl)piperazin-1-yl)ethyl)isobenzofuran-1(3H)-one.

Authors: Haifeng Tang, Reynald K de Jesus, Shawn P Walsh, Yuping Zhu, Yan Yan, Birgit T Priest, Andrew M Swensen, Magdalena Alonso-Galicia, John P Felix, Richard M Brochu, Timothy Bailey, Brande Thomas-Fowlkes, Xiaoyan Zhou, Lee-Yuh Pai, Caryn Hampton, Melba Hernandez, Karen Owens, Sophie Roy, Gregory J Kaczorowski, Lihu Yang, Maria L Garcia, Alexander Pasternak

Journal, date & volume: Bioorg. Med. Chem. Lett., 2013 Nov 1 , 23, 5829-32

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24075732


Abstract
A sub-class of distinct small molecule ROMK inhibitors were developed from the original lead 1. Medicinal chemistry endeavors led to novel ROMK inhibitors with good ROMK functional potency and improved hERG selectivity. Two of the described ROMK inhibitors were characterized for the first in vivo proof-of-concept biology studies, and results from an acute rat diuresis model confirmed the hypothesis that ROMK inhibitors represent new mechanism diuretic and natriuretic agents.