Synthesis, structure and antiarrhythmic properties evaluation of new basic derivatives of 5,5-diphenylhydantoin.
The synthesis of 1-N and 3-N aminoalkyl derivatives of 5,5-diphenylhydantoin is described. Structural elucidation based on X-ray analysis was performed for two representative compounds 4a and 9b. The effect of tested compounds on the electrocardiogram was examined in vitro in the non-working heart perfusion test and antiarrhythmic activity in the rat coronary artery ligation-reperfusion model. The most active 1-N derivatives 4a and 7b have shown properties of the compounds belonging to class Ia, according to the Vaughan Williams classification. The spatial organisation of the chosen compounds necessary for their pharmacological activity was discussed.
Kieć-Kononowicz
Katarzyna
K
Jagiellonian University Medical College, Department of Chemical Technology of Drugs, Medyczna 9, PL 30-688, Kraków, Poland. mfkonono@cyf-kr.edu.pl
Stadnicka
Katarzyna
K
Mitka
Agnieszka
A
Pekala
Elzbieta
E
Filipek
Barbara
B
Sapa
Jacek
J
Zygmunt
Małgorzata
M
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D000927:Anticonvulsants / Q000737:chemistry; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000209:etiology; D018360:Crystallography, X-Ray; D015428:Myocardial Reperfusion Injury / Q000150:complications; D010672:Phenytoin / Q000031:analogs & derivatives* / Q000737:chemistry; D051381:Rats
D000889:Anti-Arrhythmia Agents; D000927:Anticonvulsants; D010672:Phenytoin