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ACS Med Chem Lett. 2015 May 7;6(7):747-52. doi: 10.1021/ml500440u. eCollection 2015 Jul 9.

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

Author information

1
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.

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.

KEYWORDS:

ROMK; diuresis; heart failure; hypertension; natriuresis

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