1-[(3-Aryloxy-3-aryl)propyl]-1H-imidazoles, New Imidazoles with Potent Activity againstCandida albicansand Dermatophytes. Synthesis, Structure−Activity Relationship, and Molecular Modeling Studies

New 1-[(3-aryloxy-3-aryl)propyl]-1 H -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.