Synthesis and in vitro pharmacology of a series of hybrid molecules possessing 1,4-dihydropyridine calcium-channel blocking activity and histamine H₂-agonistic properties

The synthesis and in vitro pharmacology of a series of new cardiovascular hybrid molecules, which could be useful for the treatment of certain types of hypertension and at the same time for the treatment of cardiac ischemic disease, are discussed. Two types of 1,4-dihydropyridine Ca²⁺-channel blockers have been studied. In general, hybrid molecules possessing a diethyl 2-(ω-aminoalkylthio)methyl-2,6-dimethyl-4-[(substituted)phenyl]-1,4-dihydropyridine-3,5-dicarboxylic structural moiety and a histamine H₂-agonistic structural moiety are more potent L-type calcium-channel blockers and histamine H₂-agonists than hybrid molecules containing a diethyl 4-[2-(ω-aminoalkoxy)phenyl]-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic structural moiety.