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Studies on Antifungal Agents. Part 22. 3‐aryl‐5‐[(aryloxy)alkyl]‐3‐[(1 H ‐imidazol‐1‐yl)methyl]‐2‐methylisoxazolidines and related derivatives
Author(s) -
Mullen George B.,
Swift Patricia A.,
Marinyak David M.,
Allen Stanley D.,
Mitchell Jeffrey T.,
Kinsolving C. Richard,
Georgiev Vassil St.
Publication year - 1988
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19880710406
Subject(s) - chemistry , aryl , ketoconazole , candida albicans , stereochemistry , alkyl , trichophyton rubrum , cycloaddition , potency , antifungal , antifungal drugs , minimum inhibitory concentration , in vitro , organic chemistry , microbiology and biotechnology , biochemistry , biology , catalysis
The synthesis and antifungal activity of a novel series of 3‐aryl‐5‐[(aryloxy)alkyl]‐3‐[(1 H ‐imidazol‐1‐yl)‐methyl]‐2‐methylisoxazolidines and related compounds, are discussed. The synthesis of the title compounds was accomplished via a 1,3‐dipolar cycloaddition of α‐substituted ketonitrones with l‐alkenyl phenyl ethers (Scheme 2 and 3). The compounds were evaluated for in vitro antifungal activity in solid agar cultures against a broad variety of yeast and systemic mycoses and dermatophytes. While antifungal activity was evident throughout the series, in general, derivatives having halogen atom(s) in either or both aryl rings demonstrated the highest potency, especially against Trichophyton rubrum and Candida albicans . The dichloro analog 20 (PR 967‐248) was found to possess the most useful activity. Its minimum inhibitory concentration ( MIC ) values ranged between 0.2 and 2.0 μg/ml, as compared to 0.2–20.0 μg/ml for the standard drug ketoconazole (4).