| Literature DB >> 28111141 |
Harry R Chobanian1, Yan Guo1, Barbara Pio1, Haifeng Tang1, Nardos Teumelsan1, Matthew Clements1, Jessica Frie1, Ronald Ferguson1, Zach Guo1, Brande S Thomas-Fowlkes2, John P Felix2, Jessica Liu2, Martin Kohler2, Birgit Priest2, Caryn Hampton3, Lee-Yuh Pai3, Aaron Corona3, Joseph Metzger3, Vincent Tong4, Elizabeth M Joshi4, Ling Xu4, Karen Owens4, Kevin Maloney5, Kathleen Sullivan3, Alexander Pasternak1.
Abstract
A spirocyclic class of ROMK inhibitors was developed containing a structurally diverse heterocyclic sulfone moiety and spirocyclic core starting from lead 1. These compounds not only displayed exquisite ROMK potency but significantly improved selectivity over hERG. The lead compounds were found to have favorable pharmacokinetic properties and displayed robust diuretic, natriuretic and blood pressure lowering effects in spontaneously hypertensive rats.Entities:
Keywords: Diuresis; Heart Failure; Heterocyclic sulfone; Hypertension; Natriuresis; ROMK
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Year: 2016 PMID： 28111141 DOI： 10.1016/j.bmcl.2016.10.032
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823