Discovery of a novel potent Na+/Ca2+ exchanger inhibitor: design, synthesis and structure–activity relationships of 3,4-dihydro-2(1H)-quinazolinone derivatives

Design, synthesis and structure–activity relationships for 3,4-dihydro-2(1H)-quinazolinone derivatives with the inhibitory activities of the Na+/Ca2+ exchanger are discussed. These studies based on lead compound 1a lead to the discovery of a structurally novel and highly potent inhibitor against the Na+/Ca2+ exchanger 4f (SM–15811), which directly inhibited the Na+-dependent Ca2+ influx via the Na+/Ca2+ exchanger in cardiomyocytes with a high potency.