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

A new subseries of ROMK inhibitors exemplified by <b>28</b> has been developed from the initial screening hit <b>1</b>. The excellent selectivity for ROMK inhibition over related ion channels and pharmacokinetic properties across preclinical species support further preclinical evaluation of <b>28</b> as a new mechanism diuretic. Robust pharmacodynamic effects in both SD rats and dogs have been demonstrated