Imidazoles antifungal activity

Insertion of a triazole ring in place of an imidazole ring is consistent in some cases with retention of antifungal activity. The synthesis of one such agent, azoconazole (64), proceeds simply by displacement of halide with 1,2,4-triazole. The route to terconazole (65) is rather like that to ketoconazole (34). ... 

Ethonam (99), an imidazole derivative with a very different substitution pattern, is also reported to possess antifungal activity. To prepare it, alkylation of aminotetralin 94 with methylchloro-acetate gives the glycine derivative 95. Heating with formic acid then affords the amide 96 this compound is then reacted with ethyl formate to yield hydroxymethylene ester 97. Reaction with isothio-cyanic acid gives the imidazole-2-thiol 98. (The... 

Based on their initial leads, Janssen launched a series of imidazole antifungals (Fig. 5.2), miconazole (7), econazole (8), and ketoconazole (11), which were complemented by clotrimazole (10, Bayer) and tioconazole (9, Pfizer). With the exception of ketoconazole, all were characterized by potent antifungal activity but very low systemic exposure hence, they were limited to topical application for skin or nail infections. 

It is orally effective broad spectrum imidazole antifungal drug. It is useful in both dermatophytosis and deep mycosis. Oral absorption is facilitated by gastric acidity. It is highly protein bound, metabolised in liver and metabolites are excreted in urine and faeces. Its spectrum is similar to that of miconazole and is more active against Coccidioides. 

Ketoconazole [kee toe KON a zole], a substituted imidazole, is one of a family of azoles useful in treating systemic mycoses. In addition to its antifungal activity, ketoconazole also inhibits gonadal and adrenal steroid synthesis in humans by blocking C17-20 lyase, Up-hydroxylase, and cholesterol side-chain cleavage thus, it suppresses testosterone and cortisol synthesis. 

Di Santo R, Costi R, Artico M et al (1997) Antifungal estrogen-like imidazoles. Synthesis and antifungal activities of thienyl and l//-pyrrolyl derivatives of l-aryl-2-(l/f-imidazol-l-yl)ethane. Eur J Med Chem 32 143-149... 

The butoconazole nitrate vaginal cream, 2%, contains butoconazole nitrate 2%, an imidazole derivative with antifungal activity. Its chemical name is ( )-l-[4-(p-chlo-rophenyl)-2-[(2,6-dichlorophenyl)thio]butyl] imidazole mononitrate. It contains 2% butoconazole nitrate in a cream of edetate disodium, glyceryl monoisostearate, methylparaben, mineral oil, polyglyceryl-3 oleate, propylene... 

Tioconazole, an imidazole derivative with antifungal activity (vaginal ointment 6.5%), is used in the treatment of vulvovaginal candidiasis. 

Vanden Bossche, H., G. Willemsens, W. Cools, P. Marichal and W. Lauwers (1983). Hypothesis on the molecular basis of the antifungal activity of N-substituted imidazoles and triazoles. Biochem. Soc. Trans. 11, 665-667. 

Many Hj antihistamines are metabolized by CYPs. Thus, inhibitors of CYP activity such as macrolide antibiotics (e.g., erythromycin) or imidazole antifungals (e.g.,ketoconazole) can increase Hj antihistamine levels, leading to toxicity. Some newer antihistamines, such as cetirizine, fexofenadine, levocabastine, and acrivastine, are not subject to these drug interactions. 

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