Ketoconazole has a broad spectrum of antifungal activity, including many Candida infections. It possesses fungicidal and fungistatic activity with respect to dermatophytes, yeast fungus, dimorphous fungi, and eumycetes. It is also active with respect to staphylococci and streptococci. It is effective for chronic diseases, treating fungal infections of the gastrointestinal tract, sex organs, skin, hair, and nails. It is used in combination with shampoo for treating and preventing mycelial fungi, seborrheic dermatitis, and dandruff. Synonyms of this drug are nizoral and others.
Miconazole: Miconazole, 1-[2,4-dichloro-P-[(2,4-dichlorobenzyl)oxy]phenethyl]-imidazole (35.2.7), like ketoconazol, is synthesized from 2,4-dichlorophenacylbromide, which is reacted with imidazole to make 1-(2,4-dichlorobenzoylmethyl)-imidazole[2,4-dichloro-ra-(1-imida-zolyl)-acetophenone] (35.2.5). Reducing the carbonyl group in this molecule with sodium borohydride gives 1-(2,4-dichlorophenyl)-3-(1-imidazolyl)-ethanol (35.2.6), and the hydroxyl group is alkylated by 2,4-dichlorobenzylbromide using a powerful base such as sodium hydride to make miconazole (35.2.7) [22-24].
Miconazole is primarily used externally for candida and dermatophyte infections of the skin and vaginal candidosis as well as for acute internal mycoses. Synonyms of this drug are acnidazil, dactar, dermonistate, and others.
Econazole: Econazole, 1-[2,4-dichloro-P-[(4-chlorobenzyl)oxy]phenethyl]-imidazole (35.2.8), is an analog of myconazole. It differs in the presence of a single chlorine atom in the benzyl part of the molecule, and it is synthesized in the same manner, except that it uses 4-chlorobenzylchloride in the last stage instead of 2,4-dichlorobenzylbromide [22-24].
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Econazole is also used externally (only superficially) to treat ringworm and candidoses caused by flora that are sensitive to this drug (Trichophiton rubrum, Trichophiton menta-grophytes, Trichophiton tonsurans, Microsporum canis, Microsporum audouini, Microsporum gypseum, Candida albicans). When used locally, it kills fungi in three days. Synonyms of this drug are pevaryl, exostatin, dermazol, and others.
Sulconazole: Sulconazole, 1-[2,4-dichloro-P-[(4-chlorobenzyl)thio]phenethyl]-imidazole (35.2.9), is an analog of exonazole. It differs in the replacement of the etheral oxygen bridge (which connects the 4-chlorobenzyl part of the molecule with phenethylimidazole) for a thioether bond. The corresponding changes in the synthesis of this drug are the replacement of the hydroxyl group in 1-(2,4-dichlorophenyl)-2-(1-imidazolyl)-ethanol (35.2.6) with a chlorine atom using thionyl chloride, followed by a reaction of the resulting chloride with 4-chlorobenzylmercaptane to make sulconazole [25,26].
Like econazole, sulconazole is used externally (only superficially) for the same indications as econazole. Synonyms of this drug are exelderm, sulcosyn, and others.
Butoconazole: Butoconazole, 1-[4-(4-chlorophenyl)-2-[(2,6-dichlorophenyl)thio]butyl]-lH-imidazole (35.2.12), is synthesized from 4-chlorobenzylmagnesium bromide, which is reacted with epichloridrine to make 4-(4'-chlorophenyl)-1-chlorobutan-2-ol (35.2.10), which is reacted with imidazole in the presence of sodium to make 4-(4'-chlorophenyl)-1-(1H-imidazolyl)butanol-2 (35.2.11). The hydroxyl group in the last is replaced with a chlorine atom upon reaction with thionyl chloride, which is then by the reaction with 2,6-dichlorothiophenol butoconazole [27,28], is obtained.
CH2MgBr + ^-CH^Cl -»- Cl—<( y— CH2-CH2-CH-CH2-Cl
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