Synthesis and Antiarrhythmic Activity of New Benzofuran Derivatives

Article abstract of DOI:10.1021/jm00134a007

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 derivativesN-<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 diisopyramide and have been selected for further studies.