Synthesis, structure-activity relationship of some new anti-arrhythmic 5-arylidene imidazolidine-2,4-dione derivatives

The synthesis of unsubstituted and halogen substituted 5-arylidene basic amide derivatives of imidazolidine-2,4-dione is described. Structural elucidation based on X-ray analysis was performed for four representative compounds. The effect of the studied compounds on the electrocardiogram was examined in vitro in the non-working heart perfusion test and that of an anti-arrhythmic activity in the rat coronary artery ligation-reperfusion model. The most active compound: (5Z)-(3-chloro)benzylidene-3-{2-[4-(hydroxyethyl)piperazin-1-yl]-2-oxoethyl}imidazolidine-2,4-dione has shown properties of the compounds belonging to class Ia, according to the Vaughan Williams classification. Chosen compounds evaluated in vivo were devoid of anticonvulsant and neurotoxical activity.