1-[(3-Aryloxy-3-aryl)propyl]-1H-imidazoles, New Imidazoles with Potent Activity against Candida albicans and Dermatophytes. Synthesis, Structure−Activity Relationship, and Molecular Modeling Studies
New 1-[(3-aryloxy-3-aryl)propyl]-1H-imidazoles were synthesized and evaluated against Candida albicans and dermatophytes in order to develop structure−activity relationships (SARs). Against C. albicans the new imidazoles showed minimal inhibitory concentrations (MICs) comparable to those of ketocona...
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Published in | Journal of medicinal chemistry Vol. 51; no. 13; pp. 3841 - 3855 |
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Main Authors | , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
WASHINGTON
American Chemical Society
10.07.2008
Amer Chemical Soc |
Subjects | |
Online Access | Get full text |
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Summary: | New 1-[(3-aryloxy-3-aryl)propyl]-1H-imidazoles were synthesized and evaluated against Candida albicans and dermatophytes in order to develop structure−activity relationships (SARs). Against C. albicans the new imidazoles showed minimal inhibitory concentrations (MICs) comparable to those of ketoconazole, miconazole, and econazole, and were more potent than fluconazole. Several derivatives (10, 12, 14, 18−20, 24, 28, 29, 30, and 34) turned out to be potent inhibitors of C. albicans strains resistant to fluconazole, with MIC values less than 10 µg/mL. Against dermatophytes strains, compounds 20, 25, and 33 (MIC ≤ 5 µg/mL) were equipotent to ketoconazole, econazole, and miconazole. SARs of imidazoles 10−44 were rationalized with reasonable accuracy by a previously developed quantitative pharmacophore for antifungal agents. |
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Bibliography: | ark:/67375/TPS-P01TFK1H-R Addional information on computational investigations. This material is available free of charge via the Internet at http://pubs.acs.org. istex:AC5A961CCA132B9FBAAD05E70963EA291C1A3C77 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0022-2623 1520-4804 |
DOI: | 10.1021/jm800009r |