Synthesis and Antiarrhythmic Activity of New Benzofuran Derivatives

Abstract

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]- -methylurea (8m) showed advantages when compared to quinidine and disopyramide and have been selected for further studies. © 1981, American Chemical Society. All rights reserved.