N-[(omega-amino-1-hydroxyalkyl)phenyl]methanesulfonamide derivatives with class III antiarrhythmic activity
| Autor: | J. K. Gibson, Jackson B. Hester, M. G. Cimini, B. E. West, Louis L. Skaletzky, P. K. Locker, J. K. Sykes, D. E. Emmert, S. C. Perricone |
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| Rok vydání: | 1991 |
| Předmět: |
Male
Magnetic Resonance Spectroscopy Tertiary amine Refractory period Heart Ventricles Myocardial Infarction Pharmacology In Vitro Techniques Structure-Activity Relationship Dogs Drug Discovery medicine Animals Ventricular Function Papillary muscle Sulfonamides Molecular Structure Cardiac electrophysiology Chemistry Ibutilide Fumarate Sotalol Effective refractory period Biological activity Arrhythmias Cardiac Heart Myocardial Contraction medicine.anatomical_structure Biochemistry cardiovascular system Molecular Medicine Female Indicators and Reagents Rabbits Anti-Arrhythmia Agents medicine.drug |
| Zdroj: | Journal of medicinal chemistry. 34(1) |
| ISSN: | 0022-2623 |
| Popis: | N-[4-[4-(Ethylheptylamino)-1-hydroxybutyl]phenyl]methanesulfonamid e, (E)-2-butenedioate (2:1) salt (ibutilide fumarate, 2E), has been found to have Class III antiarrhythmic activity. In an in vitro rabbit heart tissue preparation designed to evaluate the cardiac electrophysiology of potential antiarrhythmic agents, it selectively prolongs the effective refractory period of papillary muscle. In vivo it increases the ventricular refractory period of the canine heart and prevents the ventricular arrhythmias induced by programmed electrical stimulation 3-9 days after a myocardial infarction. This paper describes the synthesis of 2E and a series of related compounds. The in vitro evaluation of the cardiac electrophysiology of these compounds has allowed us to determine the structural requirements for Class III antiarrhythmic activity in this series. Evaluation of the antiarrhythmic activity of 2E and one of the more potent analogues on the late postinfarction ventricular arrhythmias induced by programmed electrical stimulation of the canine myocardium is also described. This activity is compared with that of the Class III antiarrhythmic agent sotalol. Compound 2E appears to be as effective and 10-30 times more potent than sotalol in this model. |
| Databáze: | OpenAIRE |
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