5-{[aryl or aryloxy (or io)]methyl}-3-(1H-imidazol-1-ylmethyl)-3-(2-thienyl)-2-methylisoxazolidine derivatives as novel antifungal agents

Article abstract of DOI:10.1002/jps.2600771213

The in vitro antifungal activity of a novel series of cis- and trans-5{[aryl or aryloxy (or io)methyl}-3-(1H-imidazol-1-ylmethyl)-3-(2-thienyl)-2-methylisoxazolidines (13-24) was evaluated and compared with ketoconazole. The title series of compounds was prepared via a 1,3-dipolar cycloaddition reaction of 1-(2-thienyl)-2-(1H-imidazol-1-yl)-N-methylethanimine N-oxides with appropriate styrenes, allyl phenyl esters, or allyl phenyl thioether precursors. The resulting products were mixtures of the corresponding cis- and trans-diastereomers which were readily separated by flash chromatography on neutral silica gel. The majority of compounds 13-24, when tested in solid agar cultures, exhibited moderate to potent activity against Trichophyton rubrum, Aspergillus fumigatus, and Candida albicans at concentrations ranging between ≤2.0 and 70.0 μg/mL.