RESUMEN
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.
Asunto(s)
Antifúngicos/síntesis química , Cetoconazol/análogos & derivados , Triazoles/síntesis química , Animales , Aspergillus fumigatus/efectos de los fármacos , Candida/efectos de los fármacos , Candidiasis Vulvovaginal/tratamiento farmacológico , Cryptococcus neoformans/efectos de los fármacos , Dermatomicosis/tratamiento farmacológico , Femenino , Cobayas , Itraconazol , Cetoconazol/síntesis química , Cetoconazol/uso terapéutico , Microsporum/efectos de los fármacos , Phialophora/efectos de los fármacos , Ratas , Ratas Endogámicas , Sporothrix/efectos de los fármacos , Triazoles/uso terapéutico , Trichophyton/efectos de los fármacosRESUMEN
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.
Asunto(s)
Antifúngicos/síntesis química , Imidazoles/síntesis química , Piperazinas/síntesis química , Animales , Candidiasis/tratamiento farmacológico , Fenómenos Químicos , Química , Femenino , Cobayas , Imidazoles/farmacología , Imidazoles/uso terapéutico , Miconazol/uso terapéutico , Piperazinas/farmacología , RatasRESUMEN
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.
