Imidazole antifungals

M. Ogata, Synthesis of Antifungal Imidazoles and Triazoles, Ann. N.Y. Acad. Sci. 544, 113-127 (1988). H. Staab u. W. Rohr, in W. Foerst, Synthesen mit heterocyclischen Amiden (Azoliden) Neuere Methoden... 

Rittenhouse, A. R., Vandorpe, D. H., Brugnara, C., and Alper, S. L. 1997. The antifungal imidazole clotrimazole and its major in vivo metabolite are potent blockers of the calcium-activated channel in murine erythroleukemia cells. 1. Membr. Biol. 157 177-191. 

Antifungal imidazoles (ketoconazole, itraconazole, and analogues) compete for hepatic oxidative pathways that metabolize most benzodiazepines, as well as zolpidem, zopiclone, and buspirone (SEDA-22, 39, 41-43). 

Displacement of bromine on phenacyl halide with imidazole gives Reduction with sodium borohydride followed by displacement with 2,6-dichloro-benzyl alcohol in HMPA then produces antifungal orconazole (37). ... 

If the displacement reaction is carried out between imidazole derivative and thiophene analogue the antifungal agent tiaconazole (40) results. A rather slight variant of... 

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). ... 

Nafimidone (93), an anticonvulsant compound, also contains an imidazole moiety It seems to have been discovered by accident during a search for antifungal agents Its synthesis is straightforward involving displacement with imidazole of the activated chlorine atom of chloro-methyl-p-naphthylketone (92) [32]... 

Bifonazole (109) is claimed to be remarkably non-toxic and is marketed as a topical antifungal agent overseas. It can be conveniently synthesized in the by now familiar way by reduction of p-phenylbenzophenone (108) with borohydride, conversion to the chloride with thionyl chloride, and then imidazole displacement to bifonazole (109) [39]. 

Antifungal drugs are classified according to their mode of action and/or their chemical class. Four chemical classes have mainly contributed to the actual armentory of antifungal drugs the broadest class is the one of azoles (imidazoles and triazoles), followed by polyenes, allylamines and morpholines. Some individual compounds are used in dermatology. 

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... 

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... 

Khashaba et al. [34] suggested the use of sample spectrophotometric and spectrofluorimetric methods for the determination of miconazole and other antifungal drugs in different pharmaceutical formulations. The spectrophotometric method depend on the interaction between imidazole antifungal drugs as -electron donor with the pi-acceptor 2,3-dichloro-5,6-dicyano-l,4-benzoquinone, in methanol or with p-chloranilic acid in acetonitrile. The produced chromogens obey Beer s law at Amax 460 and 520 nm in the concentration range 22.5-200 and 7.9-280 pg/mL for 2,3-dichloro-5,6-dicyano-l,4-benzoquinone and p-chloranilic acid, respectively. Spectrofluorimetric method is based on the measurement of the native fluorescence of ketoconazole at 375 nm with excitation at 288 nm and/or fluorescence intensity versus concentration is linear for ketoconazole at 49.7-800 ng/mL. The methods... 

Fucicort contains fusidic acid (antibacterial) and betamethasone (corticosteroid), which is more potent than hydrocortisone (corticosteroid). Fucidin H contains fusidic acid and hydrocortisone Daktacort contains miconazole (imidazole antifungal) and hydrocortisone Canesten HC contains clotrimazole (imidazole antifungal) and hydrocortisone. Otosporin contains hydrocortisone in combination with two antibacterial agents, namely neomycin and polymyxin. 

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