A Novel Class of Sodium/Calcium Exchanger Inhibitors: Design, Synthesis and Structure—Activity Relationships of 4-Phenyl-3-(piperidin-4-yl)-3,4-dihydro-2(1H)-quinazolinone Derivatives.

Abstract Design, synthesis, and structure–activity relationships of 3,4-dihydro-2(1H)-quinazolinone derivatives as sodium/calcium (Na+/Ca2+) exchanger inhibitors are described. In these studies, optimization of the substituents at the 3-position of this series of compounds was carried out and dramatic effects of the substituent on the activities were observed. Based on these SAR studies, a highly potent inhibitor of the Na+/Ca2+ exchanger, which showed single-digit-nanomolar activity, was discovered.