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

ACS Med Chem Lett

Discovery Chemistry, Department of Pharmacology, Department of Cardiometabolic Diseases, Pharmacokinetic, Pharmacodynamics and Drug Metabolism, Department of Chemistry Modeling and Informatics, Merck Research Laboratories , Kenilworth, New Jersey 07033, United States.

Published: July 2015


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Article Abstract

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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4499836PMC
http://dx.doi.org/10.1021/ml500440uDOI Listing

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