Imidazole Clotrimazole

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

Imidazoles clotrimazole econazole nitrate metronidazole miconazole nitrate... 

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. 

Longstanding remedies such as Compound Benzoic Acid Ointment (Whitfield s ointment) are still acceptable for iruld infections but a topical imidazole (clotrimazole, econazole, miconazole, sulconazole), which is also effective against Candida, is now usually preferred. Tioconazole is effective topically for nail infections. If multiple areas are affected, especially if the scalp or nails are included, and if topical therapy fails, oral itraconazole or terbinafine are used. Griseofulvin has largely been superseded for these indications. 

Clotrimazole. The imidazole derivative clotrimazole (6) was iatroducedia 1969. Clotrimazole [23593-75-1] or l-((9-chloro-a,a-diphenylbenzyl)imidazole is a water-iasoluble antimycotic for topical appHcation, with a broad-spectmm activity against mycoses of the skin and the vagiaa. 

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). 

Imidazole antimycotics, ketoconazole, clotrimazole, and miconazole are potent inhibitors of various cytochrome P450-isoenzymes that also affect the metabolism of retinoids. They were fust shown to inhibit the metabolism of RA in F9 embryonal carcinoma cells. When tested in vitm liarazole, a potent CYP-inhibitor, suppressed neoplastic transformation and upregulated gap junctional communication in murine and human fibroblasts, which appeared to be due to the presence of retinoids in the serum component of the cell culture medium. Furthermore, liarazole magnified the cancer chemopreventive activity of RA and (3-carotene in these experiments by inhibiting RA-catabolism as demonstrated by absence of a decrease in RA-levels in the culture medium in the presence of liarazole over 48 h, whereas without liarazole 99% of RA was catabolized. In vivo, treatment with liarazole and ketoconazole reduced the accelerated catabolism of retinoids and increased the mean plasma all-irans-RA-concentration in patients with acute promyelocytic leukemia and other cancels. 

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... 

The mechanism of the reaction has not been eiuddated. Presumably iodine eliminates the imidazole ring from N-substituted imidazole derivatives such as clotrimazole, and this then couples with diazotized sulfanilic acid to yield an azo dye. 

Note The reaction is very specific for N-substituted imidazole derivatives. In serum investigations the detection limit was 50 ng clotrimazole per milliliter serum. The reagent can be employed on silica gel, kieselguhr and Si 50000 layers. 

Other imidazole derivatives include clotrimazole (Fig. 5.20B), miconazole (Fig. 5.20C) and econazole (Fig. 5.20D), all of which possess a broad antimycotic spectrum... 

Clotrimazole, miconazole, econazole, ketoconazole Newer imidazoles fluconazole, itraconazole... 

Fig. 5.20 Imidazoles (A-F) A, metronidazole B, clotrimazole C, miconazole D, econazole E, ketoconazole F, fluconazole G, flucytosine H, 5-fluorouracil I, terbinafme J, tolnaftate.

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. 

Athlete s foot, tinea pedis, is a condition caused by a fungus. Management of athlete s foot lies with the use of antifungal preparations such as clotrimazole (an imidazole antifungal) and tolnaftate. Salicylic acid is a keratolytic agent indicated for use in treatment of corns, calluses and warts. 

Clotrimazole is an imidazole antifungal agent indicated for the treatment of fungal infections caused by Candida albicans. The administration of clotrimazole would be of no use in the treatment of infections caused by Chlamydia trachomatis, Neisseria gonorrhoea, Staphylcoccus aureus and Streptococcus pneumoniae. 

Some imidazole derivatives have turned out to be extremely beneficial for treating fungal infections. They are ketoconazole, miconazole, clotrimazole, econazole, butoconazole, and others. 

Clotrimazole Clotrimazole, l-(o-chloro-a,a-diphenylbenzyl)imidazole (35.2.21), is synthesized by reacting 2-chlorotriphenyhnethylchloride (35.2.20) with imidazole in the presence of triethylamine [33-37]. 

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. 

Because trimetrexate is metabolized by a P450 enzyme system, drugs that induce or inhibit this drug metabolizing enzyme system may elicit important drug interactions that may alter trimetrexate plasma concentrations, which include erythromycin, rifampin, rifabutin, ketoconazole, fluconazole, cimetidine, nitrogen substituted imidazole drugs (eg, clotrimazole, ketoconazole, miconazole). 

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. 

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. 

As in the case of hydrocortisone acetate, where hydrocortisone might be expeeted to occur as a result of hydrolysis of the acetate ester, tests for the presenee of known impurities are based on the known manufacturing sequence or on likely degradation pathways. For example, the tests carried out on clotrimazole are based on the last step in its manufacture as shown in Figure 13.8. Unreacted imidazole is an obvious impurity and chlorotritanol would be readily formed from unreacted chlorotrityl bromide by hydrolysis, which would occur when the clotrimazole is extracted from the reaction mixture. 

Clotrimazole (Lotrimin, Gyne-Lotrimin, Mycelex) is a broad-spectrum fungistatic imidazole drug used in the topical treatment of oral, skin, and vaginal infections with C. albicans. It is also employed in the treatment of infections with cutaneous dermatophytes. 

Clotrimazole, is an imidazole derivative and has a broad antimycotic spectrum of action in vivo, which includes dermatophytes, yeasts, moulds etc. 

Apart from imidazole derivative e.g. metronidazole, tinidazole, nimorazole etc. and other agents such as hydroxy quinolines, iodine preparation (povidoneiodine) and antifungal antibiotics e.g. clotrimazole (used mainly as vaginal pessaries), there are some other compounds which are mainly used in the treatment of trypanosomiasis. They are ... 

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. 

The topical imidazoles, which currently include clotrimazole, econazole, ketoconazole, miconazole, oxiconazole, sulconazole, and sertaconazole, have a wide range of activity against dermatophytes (epidermophyton, microsporum, and trichophyton) and yeasts, including Candida albicans and Pityrosporum orbiculare (see Chapter 48). 

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