ABSTRACT
A series of novel triazol-3-ones have been synthesized, and their in vitro and in vivo antifungal properties are reported. Compound 68 (itraconazole), which displays a pronounced oral activity against vaginal candidosis in rats and against microsporosis in guinea pigs, has been selected for clinical evaluation.
Subject(s)
Antifungal Agents/chemical synthesis , Ketoconazole/analogs & derivatives , Triazoles/chemical synthesis , Animals , Aspergillus fumigatus/drug effects , Candida/drug effects , Candidiasis, Vulvovaginal/drug therapy , Cryptococcus neoformans/drug effects , Dermatomycoses/drug therapy , Female , Guinea Pigs , Itraconazole , Ketoconazole/chemical synthesis , Ketoconazole/therapeutic use , Microsporum/drug effects , Phialophora/drug effects , Rats , Rats, Inbred Strains , Sporothrix/drug effects , Triazoles/therapeutic use , Trichophyton/drug effectsABSTRACT
The preparation and antifungal properties of cis-1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl-methyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine (I) are described. Ketoconazole has, at low oral doses, a high in vivi activity against vaginal candidosis in rats and against cutaneous candidosis in guinea pigs.
Subject(s)
Antifungal Agents/chemical synthesis , Imidazoles/chemical synthesis , Piperazines/chemical synthesis , Animals , Candidiasis/drug therapy , Chemical Phenomena , Chemistry , Female , Guinea Pigs , Imidazoles/pharmacology , Imidazoles/therapeutic use , Miconazole/therapeutic use , Piperazines/pharmacology , RatsABSTRACT
The synthesis of 1-(2-alkyl-2-phenylethyl)-1H-imidazoles was accomplished starting from the corresponding phenylacetonitriles. Via alkylation, esterification, and sodium borohydride reduction-in the presence of lithium iodide-beta-phenylalconols were obtained. Mesylation of these alcohols and refluxing with imidazole in dimethylformamide furnished title compounds, which were active in vitro against dermatophytes, yeasts, other fungi, and gram-positive bacteria and in vivo as well as in vitro against Candida albicans.
