Structure-Activity Relationship of Some New Anti-Arrhythmic Phenytoin Derivatives
| Autor: | Hanna Byrtus, Maria Ciechanowicz-Rutkowska, Katarzyna Kieć-Kononowicz, Katarzyna Stadnicka, Małgorzata Zygmunt, Barbara Filipek, Dorota Maciag |
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| Rok vydání: | 2000 |
| Předmět: |
Models
Molecular Tertiary amine Imidazolidinone Chemistry Stereochemistry medicine.drug_class Molecular Conformation Pharmaceutical Science Heart Protonation Biological activity Carboxamide In Vitro Techniques Ring (chemistry) Chemical synthesis Rats Structure-Activity Relationship Heart Rate Coronary Circulation Phenytoin Drug Discovery medicine Animals Structure–activity relationship Anti-Arrhythmia Agents |
| Zdroj: | Archiv der Pharmazie. 333:357-364 |
| ISSN: | 1521-4184 0365-6233 |
| Popis: | The pharmacological activity of nine anti-arrhythmic phenytoin derivatives was assessed in preventing chloroform-induced arrhythmia. The compounds were tested in vitro on isolated heart of the rat. Four compounds were chosen as representative of the spatial characteristics of the studied group, and X-ray structure analyses were carried out on them. Because the protonated form is present in physiological milieu, conformational analysis was performed on the protonated form of the four representatives and in addition on the compound showing the highest anti-arrhythmic activity. It was found that substitution of the imidazolidinone ring of phenytoin at position 3 by a chain containing a tertiary amine nitrogen atom changes the affinity profile from inactivated (phenytoin-like) to activated (quinidine-like) cardiac sodium channels. The activity of the studied compounds relies on the presence of protonated tertiary nitrogen atom, at least one phenyl ring, and flexibility of the molecule, which enables the spacer to assume a desired length. |
| Databáze: | OpenAIRE |
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