Imidazole Miconazole nitrate

Miconazole. Miconazole nitrate [22832-87-7] (Fig. 2), the 1-phenethyl-imidazole derivative first described in 1969, interferes at low doses with the cytochrome P-450 dependent ergosterol biosynthesis in yeasts and fungi. The result is accumulation of C-14 methylated sterols on the one hand and reduction of the ergosterol levels in the membranes on the other hand (12). Analogous to clotrimazole, this leads to a disturbance in the membranes it results in inhibition of ceU repHcation, mycelium development (in C. albicans) and finally, ceU death. High concentrations of miconazole, which may be achieved with topical use, disturb the orientation of phosphoHpids in the membranes, which produces leaks (13). 

Miconazole is an imidazole antifungal agent used as miconazole base or miconazole nitrate for the treatment of superficial candidiasis and of skin infections dermato-phytosis and pityriasis versicolor. The drug has also been given intravenously by infusion for the treatment of disseminated fungal infections. Miconazole can be given by mouth in a dose of 120-240 mg, as oral gel four times daily after food, for... 

Miconazole nitrate was prepared by Godefori and co-workers [5-7]. Imidazole 1 was coupled with brominated 2,4-dichloroacetophenone 2 and the resulting ke-tonic product 3 was reduced with sodium borohydride to its corresponding alcohol 4. The latter compound 4 was then coupled with 2,4-dichlorotoluene by sodium borohydride in hexamethylphosphoramide (an aprotic solvent), which was then extracted with nitric acid to give miconazole nitrate. 

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. 

Miconazole nitrate contains not less than 99% and not more than the equivalent of 101% of (RS)-l-[2-(2,4-dichlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl]-1 //-imidazole nitrate. 

Imidazoles clotrimazole econazole nitrate ketoconazole miconazole nitrate oxiconazole nitrate tioconazole... 

Imidazoles clotrimazole econazole nitrate metronidazole miconazole nitrate... 

C3H4N2 288-32-4) see Bifonazole Butoconazole Clotrimazole Eprosartan Fenticonazole Isoconazole Ketoconazole Miconazole Neticonazole hydrochloride Omoconazole nitrate Oxiconazole Ozagrel 1/f-imidazole lithium salt (C,H3LiN2 55986-39-5) see Flutrimazole 2-imidazolidinone... 

Isoconazole. Tike econazole, both the chemical structure and the clinical indications of this imidazole derivative (Fig. 2, 7c) closely resemble those of miconazole. It is available as a vaginal tablet (300 mg isoconazole nitrate per tablet). In some countries isoconazole [27523-40-6] is also available as a cream for dermatological use and as a cream and ovules for treatment of vaginal candidosis. 

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