Mullen G B, Mitchell J T, Allen S D, St Georgiev V
Department of Organic Chemistry, Pennwalt Corporation, Rochester, NY 14623.
J Pharm Sci. 1988 Dec;77(12):1050-4. doi: 10.1002/jps.2600771213.
The in vitro antifungal activity of a novel series of cis- and trans-5-([aryl or aryloxy (or thio)]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 ethers, 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 less than or equal to 2.0 and 70.0 micrograms/mL.
评估了一系列新型顺式和反式5-([芳基或芳氧基（或硫代）]甲基)-3-(1H-咪唑-1-基甲基)-3-(2-噻吩基)-2-甲基异恶唑烷（13-24）的体外抗真菌活性，并与酮康唑进行了比较。该系列标题化合物是通过1-(2-噻吩基)-2-(1H-咪唑-1-基)-N-甲基乙亚胺N-氧化物与适当的苯乙烯、烯丙基苯基醚或烯丙基苯基硫醚前体进行1,3-偶极环加成反应制备的。所得产物是相应顺式和反式非对映异构体的混合物，可通过在中性硅胶上进行快速柱色谱轻松分离。在固体琼脂培养物中测试时，大多数化合物13-24在浓度范围小于或等于2.0至70.0微克/毫升时，对红色毛癣菌、烟曲霉和白色念珠菌表现出中度至强效活性。
