Synthesis and structure-activity relationships of benzo[b]thienylallylamine antimycotics

Benzo[b]thiophene analogues of the allylamine antimycotic terbinafine (2) bearing the side chain at various positions and optionally substituted by halogen have been prepared and their antifungal activity studied. Derivatives bearing the side chain at positions 3, 4, or 7 are bioequivalents of 2. Compounds containing the allylamine side chain at position 7, with a further substituent at position 3, showed significantly enhanced activity against Candida albicans, an effect which appears to be specifically linked only to this particular substitution pattern. 3-Chloro-7-benzo[b]thienyl derivative 7m was found to be the most potent allylamine antimycotic identified so far. In general, substituted benzo[b]thiophenes can be used not only as potential equivalents of naphthalene in bioactive compounds but also as a tool to selectively modify biological activities.