Synthesis and antiarrhythmic activity of new benzofuran derivatives.
Various 5-aminobenzofuran derivatives were prepared from khellin and screened intravenously in the dog for their potential antiarrhythmic activity against ouabain-induced ventricular arrhythmia and in the Harris test. From systematic structural variations it was found that two methoxy groups in positions 4 and 7 on the benzofuran ring, a tertiary aminoethoxy side chain in position 6, and a N-methylurea group in position 5 led to the most active compounds. These were then tested orally in the Harris test in the dog. The two long-acting derivatives N-[4,7-dimethoxy-6-(2-pyrrolidinoethoxy)-5-benzofuranyl]-N'-methylurea (8j) and N-[4,7-dimethoxy-6-(2-piperidinoethoxy)-5-benzofuranyl]-N'-methylurea (8m) showed advantages when compared to quinidine and disopyramide and have been selected for further studies.
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis*; D001572:Benzofurans / Q000138:chemical synthesis* / Q000494:pharmacology; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D001572:Benzofurans