Miconazole imidazole ring

Clotrimazole fonnally also is an imidazole derivative because of the presence of an imidazole ring in its structure. It is believed that, like miconazole, econazole, and other pure representatives of the imidazole class, it also inhibits the biosynthesis of ergosterin in the cytoplasmatic membrane of fungi. 

A number of other substituted imidazolium ions have also been reported. [MIM-C2H50CH3]Br and [MIM-CH30CH3]Br, liquids at room temperature, were recently reported to be good solvents for carbohydrates and proteins (47). The diversity of organic cations was extended even to include the antifungal drug miconazole, which contains an imidazole ring. By the reaction of the miconazole with alkyl iodide, bioactive cations were obtained that were subsequently used to form ionic liquids with PF (9). 

Ketoconazole. For treatment of systemic mycoses with amphotericin B or miconazole, the patient must be admitted to a hospital. This is not always possible, particularly in areas where systemic mycoses occur frequently, nor is it always desirable, because of the expense. For these reasons, it was desirable to find an antimycotic that combined safety and broad-spectmm activity with oral adraiinistration. Ketoconazole (10), which is orally active, met most of these requirements. This inhibitor of the ergosterol biosynthesis is an A/-substituted imidazole, that differs from its precursors by the presence of a dioxolane ring (6,7). Ketoconazole is rapidly absorbed in the digestive system after oral adrninistration. Sufficient gastric acid is required to dissolve the compound and for absorption. Therefore, medication that affects gastric acidity (for example, cimetidine and antacids) should not be combined with ketoconazole. 

Phenyl methyl ketone 1 was brominated to give l-phenyl-2-bromoethanone 2. Compound 2 was treated with methylsulfonic acid to yield the corresponding methylsulfonate 3. Etherification of 3 gave the a-benzyloxy derivative 4 and compound 4 was then chlorinated to give the 2,4-dichlorinated derivatives in both aromatic ring systems 5. Compound 5 reacted with imidazole in dimethylformamide to give miconazole 6 [7], which is converted to miconazole nitrate. 

Azoles are synthetic compounds that can be classified as either imidazoles or triazoles according to the number of nitrogen atoms in the five-membered azole ring, as indicated below. The imidazoles consist of ketoconazole, miconazole, and clotrimazole (Figure 48-2). The latter two drugs are now used only in topical therapy. The triazoles include itraconazole, fluconazole, voriconazole, and posaconazole. 

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