Bifonazole

The first stage is to prepare the naphthyl sodium solution in the following way  

To a solution of 0.6 g naphthalene in 10 ml tetrahydrofurane, anhydrous, used as solvent, add 96 mg sodium under a nittrogen atmosphere. After a few minutes, an intensive dark green coloration develops, while the sodium dissolves. The reaction is completed after a period of time ranging between 30 and 60 minutes. 

Then add to the above solution a solution of 2,42 g reserpine in 60 ml anhydrous dioxan at 50°C. 

After heating for 15 minutes (which corresponds to carrying out reaction a), add 0.6 g, di-ethylaminochloroethane, while the mixture is kept boiling under ref lux, for 6 hours. Reaction b is then completed. 

Then cool the mixture and evaporate the dioxan under reduced pressure. The pasty residue is dissolved in a mixture of 50 ml benzene and 20 ml ether, and washed several times with water. 

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Because of their limited, activity, small spectmm, and side effects, the older topical antimycotics have generally been surpassed by newer antimycotic chemotherapeutic agents. These newer antimycotics for topical use iaclude the imida2ole derivatives clotrimazole, miconazole, econazole, isoconazole, sulconazole, fenticonazole, oxiconazole, bifonazole, butoconazole, ziaoconazole, tioconazole, and the triazole derivative, terconazole (Table 2) (5—7). The iatroduction of the azole derivatives represents a milestone ia the treatment of mycoses. 

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]. 

C12H10 92-52-4) see Bifonazole Fenbufen 4-biphenylacetonitrile (C14H11N J760i-77-7) see Felbinac [3aR-(3aa,4a,5p,6aa)]-[l,l -biphenyl]-4-carboxylic acid 4-formylhexahydro-2-oxo-2fl-cyclopenta[6]furan-5-yl ester (C2iH,80j 38754-71-1) see Latanoprost [3alt-[3aa,4a(l ,35 ),5p,6aa]]-[4,4 -biphenyl]-4-carb-oxylic acid hexahydro-4-(3-hydroxy-5-phenyl-l-pentenyl)-2-oxo-21/-cyclopenta[6]furan-5-yl ester (C3 H ,05 41639-73-0) see Latanoprost... 

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... 

Zhao, Y., White, M.A., Muralidhara, B.K., Sun, L., Halpert, J.R. and Stout, C.D. (2006) Structure of microsomal cytochrome P450 2B4 complexed with the antifungal drug bifonazole insight into P450 conformational plasticity and membrane interaction. The Journal of Biological Chemistry, 281, 5973-5981. 

A ringing surfactant gel of liquid crystalline microstmcture containing the antimy-kotic bifonazole was introduced in 1995 into the German market (Bifomyk Gel). 

Benzbromarone, 127 Benzodiazepines, 48 Betaxolol, 26 Beta-blockers, 19,25,41 Biclodil, 38 Bifonazole, 93... 

Topical azole derivatives include the imidazoles bifonazole, clotrimazole, econazole, ketoconazole, miconazole, oxiconazole, lanoconazole, flutrima-zole and sertaconazole. These drugs show activity against the dermatophytes Epidermophyton, Mi-crosporum and Trichophyton. They are also effective against the yeasts Candida albicans and Pityrospo-rum orbiculare. Local side effects include pruritus, erythema and local irritation. Allergic dermatitis is rare. 

The topical antifungal bifonazole (60-2) dispenses with virtually all but the imidazole ring the intermediate (60-1) is obtained by sequential reduction of 4-phenyl-benzophenone and then reaction of the alcohol with thionyl chloride. Displacement of chlorine by imidazole gives (60-2) [65]. 

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