The imidazole antimycotic clotrimazole was first synthesized at Bayer Pharmaceuticals in 1967. Ist antimycotic activity was first reported in 1969. Clotrimazole is readily soluble in methanol, chloroform, and DMF (all > 100 mg/mL); slightly soluble in acetone (50 mg/mL), ethyl acetate (45 mg/mL), ethanol (95 mg/mL), and PEG 400 (60 mg/mL); and practically insoluble in water (< 0.01 mg/mL).

Synthesis

The synthesis of clotrimazole begins with 2-chlorobenzyl chloride, which is converted to benzotrichloride. Friedel – Crafts reaction with benzene followed by reaction with imidazole forms clotrimazole.

Indications

Topical treatment of mycoses of the skin induced or sustained by fungi such as dermatophytes, yeasts, and chromomycetes. In addition, clotrimazole is indicated for therapy of vulvovaginal mycoses caused by Candida species and Candida (Torulopsis) glabrata.

Side Effects

Topical applications, including intravaginal application, are well tolerated. Skin irritations and allergic reactions are rarely observed and seem to be mainly due to the galenic formulation (e.g. fatty preparations on acute, inflammative lesions). Allergic reactions are rarely observed.