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

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.

SUBMITTER: Walsh SP

PROVIDER: S-EPMC4499836 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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

Walsh Shawn P SP Shahripour Aurash A Tang Haifeng H Teumelsan Nardos N Frie Jessica J Zhu Yuping Y Priest Birgit T BT Swensen Andrew M AM Liu Jessica J Margulis Michael M Visconti Richard R Weinglass Adam A Felix John P JP Brochu Richard M RM Bailey Timothy T Thomas-Fowlkes Brande B Alonso-Galicia Magdalena M Zhou Xiaoyan X Pai Lee-Yuh LY Corona Aaron A Hampton Caryn C Hernandez Melba M Bentley Ross R Chen Jing J Shah Kashmira K Metzger Joseph J Forrest Michael M Owens Karen K Tong Vincent V Ha Sookhee S Roy Sophie S Kaczorowski Gregory J GJ Yang Lihu L Parmee Emma E Garcia Maria L ML Sullivan Kathleen K Pasternak Alexander A

ACS medicinal chemistry letters 20150507 7

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. ...[more]

PMID: 26191360

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