dimazole

Originator

Aterola,Roche,US,1951

Background

Dimazole (diamthazole) is an antifungal. It was withdrawn in Franch in 1972 due to neuropsychiatric reactions.

Definition

ChEBI: 6-[2-(diethylamino)ethoxy]-N,N-dimethyl-1,3-benzothiazol-2-amine is a member of benzothiazoles.

Manufacturing Process

19.4 g of 2-dimethylamino-6-hydroxybenzothiazole (MP 245°C) were sludged in a 500 cc three-necked flask with 250 cc of chlorbenzene. Then 4.4 g of sodium hydroxide flakes were added and the mixture heated with agitation to 90°C. 4 cc of water were dropped in, and the mixture then heated slowly to the boil while about 500 cc of the water-containing chlorbenzene were distilled off. 50 cc of dry chlorbenzene were then added and the distillation was continued until about 30 cc of the chlorbenzene were distilled off. The residue was the sodium salt of thiazole in chlorbenzene. To the residue were added at 90°C, 15 g of fresh distilled 1-diethylamino-2-chloroethane. The mixture was then refluxed at 133°C for three hours, then cooled to 35°C. 75 cc of water and 5 cc of (40% by volume) sodium hydroxide solution were added and the mixture stirred for one hour. The chlorbenzene layer which contained the reaction product was separated from the aqueous layer in a separatory funnel. The chlorbenzene solution was then dried with sodium sulfate for twelve hours. It was then filtered and HCl gas was passed into the chlorbenzene solution until saturated, while cooling and stirring. The dihydrochloride precipitated as a white crystalline, sandy powder. The precipitate was filtered and washed on the funnel with benzene and finally washed with ether. The filter cake was dried at 80°C to 90°C. The 2-dimethylamino-6-(βdiethylaminoethoxy)-benzothiazole dihydrochloride thus obtained is a white crystalline powder, MP 240°C to 243°C. It can be recrystallized from ethanol and ether, or methanol or acetone.
The free base, which is an oil, can be obtained from the aqueous solution of the dihydrochloride by adding dilute sodium hydroxide or sodium carbonate solution. The base is soluble in ether, methanol, ethanol, benzene and the like, but slightly soluble in water.

brand name

Asterol [as dihydrochloride] [Veterinary] (Hoffmann- LaRoche);Atelora;Aterola;Kesten;Mycotol.

Therapeutic Function

Antifungal

World Health Organization (WHO)

Dimazole, an antifungal agent, was introduced in 1951 for the treatment of tinea infections. Although the major manufacturer subsequently discontinued marketing preparations in the United States, the US Food and Drug Administration formally withdrew marketing approval for such preparations in 1977 on the grounds of their association with severe neurotoxic reactions, their potential for misuse and the availability of safer alternative products. Topical preparations of dimazole remain available in some 40 countries.

Metabolism

Not Available