Synthesis of (E)-1-(5-chlorothien-2-yl)-2-(1H-imidazol-1-yl)ethanone 2,6-dichlorophenylhydrazone hydrochloride, a novel, orally active antifungal agent.
The preparation, determination of isomeric configuration, and antifungal properties of (E)-1-(5-chlorothien-2-yl)-2-(1H-imidazol-1-yl)ethanone 2,6-dichlorophenylhydrazone hydrochloride (1) are described. In vitro, compound 1 has been shown to have activity against Candida albicans comparable with miconazole. When administered orally to animals with experimentally induced vaginal candidiasis or systemic candidiasis, compound 1 produced results approaching those produced by ketoconazole. In addition, topical administration of compound 1 to rats with vaginal candidiasis produced results comparable with those produced by similar administration of clotrimazole. Unlike ketoconazole, which is active by a mechanism that is essentially fungistatic, compound 1 shares with miconazole a mode of action that is fungicidal. However, unlike miconazole, compound 1 exhibits activity following oral administration. Compound 1 has been found to be negative in the Ames test.
D000818:Animals; D000935:Antifungal Agents; D002176:Candida albicans / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D007654:Ketoconazole; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008825:Miconazole / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000935:Antifungal Agents; D007093:Imidazoles; D010879:Piperazines; D008825:Miconazole; C037600:1-(5-chlorothien-2-yl)-2-(1H-imidazol-1-yl)ethanone 2,6-dichlorophenylhydrazone; D007654:Ketoconazole