Clotrimazole: Clotrimazole, 1-(o-chloro-a,a-diphenylbenzyl)imidazole (35.2.21), is synthesized by reacting 2-chlorotriphenylmethylchloride (35.2.20) with imidazole in the presence of triethylamine [33-37].
The starting substance 2-chlorotriphenylmethylchloride is made in various ways. In particular, chlorinating 2-chlorotoluene under light makes 2-chlorotrichloromethylbenzene (35.2.22), which is reacted with benzene in the presence of aluminum chloride to give 2-chlorotriphenylmethylchloride (35.2.20).
An alternative way of making 2-chlorotriphenylmethylchloride is a Grignard reaction between 2-chlorobenzolphenone and phenylmagnesium bromide, followed by substitution of the hydroxyl group in the resulting 2-chlorotriphenylmethylcarbinol (35.2.23) with a chlorine using thionyl chloride.
And finally, reacting phosphorous pentachloride with 2-chlorobenzophenone gives 2'-chloro-1,1-dichlorodiphenylmethane (35.2.24), which is used for the alkylation of benzene in the presence of aluminum chloride and gives 2-chlorotriphenylmethylchloride (35.2.20).
Clotrimazole formally 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.
In terms of pharmacological action, clotrimazole is very similar to miconazole. It has a broad spectrum of antifungal activity. It is effective with respect to dermatophytes, and it also has an antimicrobial effect against streptococci and staphylococci. It is also effective with respect to trichomonases. It is very widely used, both externally and vaginally for treating superficial infections. Synonyms of this drug are canesten, empecid, lotrimin, micosporin, and others.
Naftifine is the first representative of a new class of antifungal drugs (naftifine, terbinafine (lamisil), amorolfine, butenafine) classified as allylamines.
Naftifine: Naftifine, (E)-N-methyl-N-(3-phenyl-2-propenyl)-1-naphthalinmethanamine (35.3.1), is synthesized by alkylating N-methyl-(1-naphthylmethyl)-amine with cinnamyl chloride in the presence of sodium carbonate [38-43].
Naftifine is only permitted to be used externally and only superficially as a drug with a broad spectrum of action against dermatophytes and candida infections. According to the initial data, it exceeds the activity of econazole. Moreover, it does not have a locally irritating effect. It is believed that the fungicide activity of this drug is based on its ability to inhibit the fungal enzyme squalene epoxidase, thus lowering the concentration of ergos-terol. The corresponding enzyme in mammals is inhibited significantly less. Synonyms of this drug are exoderil, naftin, and others.
Griseofulvin: Griseofulvin, 7-chloro-2',4,6-trimethoxy-6'-methylspiro[benzofuran-2(3H),1'--cyclohexen]-3',4-dione (35.4.1), is an antibiotic produced by the mycelial fungus Penicillium patulum [44-51].
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