The chemical structure of compounds found to possess antiarrhythmic activity covers a wide range, and because of this great structural heterogenicity, efforts to determine a definitive structure have not been too successful. Even some of the more recently discovered and currently used antiarrhythmic drugs were synthesized for quite different purposes, and routine pharmacological screening and clinical trials revealed their antiarrhythmic activity.
The first extensive reviews on the SAR of antiarrhythmic drugs were by Szekeres and Papp (38) and Conn (39). These investigations indicated that most antiarrhythmic drugs possess a tertiary amine group that appears to be a key component for activity. The presence of aromatic ring system is important, and this moiety is usually connected to the tertiary amine via a hydroxy substituted alkyl chain ester or amide group. The methoxy group on the aromatic ring may enhance activity. Since these early studies the number of compounds synthesized and tested for antiarrhythmic activity has increased dramatically. The structure activity relationships and approaches to new antiarrythmic agents of some class I antiarrhythmic agents are highlighted below.
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