What is ketoconazole used to treat?

Ketoconazole is soluble in methanol, ethanol, and chloroform; slightly soluble in dilute acids; and barely soluble in water. The imidazole antimycotic ketoconazole was first synthesized at Janssen Pharmaceuticals.

Trade Names

Candoral (Ache), Cet- ´ onax (Cilag), Fitonal (Disprovent), Fungarest (Janssen), Fungicil (Labinca), Fungo-Hubber (Hubber), Fungoral (Ilsan, Janssen, Leo), Ketazol (Exa), Ketoderm (Janssen), Ketoisdin (Isdin), Ketonan (IMA), Ketoral (Bilim), Micoral (Cassara), Micotek (Kressfor), Micoticum (Vita), Nizoral (Abic, Edward Keller, Janssen), Nizshampoo (Janssen), Oromycosal (Alkaloid), Oronazol (Krka), Panfungol (Esteve), Rofenid (Rhone-Poulenc), Terzolin (Janssen).

Synthesis

The synthesis of ketoconazole begins with the ketalization of 2,4- dichloroacetophenone (1) with glycerol. The intermediate (2) is not isolated but treated with bromine to form the bromide (3). The benzoxylation of (3) gives (4) in the form of a cis – trans mixture. The cis form can be separated by crystallization. The reaction of (4) with imidazole in dimethylacetamide gives (5), which is then hydrolyzed to (6), which in turn is converted with methanesulfonyl chloride into the sulfonate (7). The reaction of (7) with the sodium salt of Nacetyl-N-p-hydroxyphenylpiperazine in DMSO gives ketoconazole.

Indications

Systemic therapy of dermatomycoses, blastomycosis, coccidioidomycosis, and histoplasmosis. Because of the side effects of ketoconazole, the newer azoles such as fluconazole and itraconazole should be considered instead of ketoconazole for systemic treatment. Ketoconazole is especially indicated in topical therapy of dermatomycoses, pityriasis versicolor, seborrheoic dermatitis, and dandruff.