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.
Pekala
Elzbieta
E
Department of Chemical Technology and Biotechnology of Drugs, Jagiellonian University Medical College, ul. Medyczna 9, 30-688 Kraków, Poland.
Stadnicka
Katarzyna
K
Broda
Agnieszka
A
Zygmunt
Małgorzata
M
Filipek
Barbara
B
Kieć-Kononowicz
Katarzyna
K
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000927:Anticonvulsants / Q000737:chemistry; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000209:etiology; D018360:Crystallography, X-Ray; D006321:Heart / Q000187:drug effects; D048289:Imidazolidines / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D015394:Molecular Structure; D015425:Myocardial Reperfusion; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D000889:Anti-Arrhythmia Agents; D000927:Anticonvulsants; D048289:Imidazolidines