Azacosterol dihydrochloride Chemical Properties

alpha 

D -32°

EPA Substance Registry System

Azacosterol hydrochloride (1249-84-9)

Safety Information

Toxicity

LD50 orl-rat: 470 mg/kg 85ARAE 3,100,76/77

Azacosterol dihydrochloride Usage And Synthesis

Description

Azacosterol hydrochloride is a diaza derivative of cholesterol which acts as a hypocholesteremic agent by blocking delta-24-reductase causing accumulation of desmosterol.

Originator

Ornitrol,Avitrol Corporation

Uses

Chemosterilant, avian.

Manufacturing Process

A solution of 15 parts of 3β-hydroxyandrost-5-en-17-one and 30 parts of 3- dimethylaminopropylamine in 36.6 parts of formic acid is heated in an oil bath at about 170-180°C for about 24 hours. The cooled mixture is diluted with about 500 parts of water, and the resulting aqueous mixture is extracted with chloroform, containing a small amount of methanol. The organic layer is separated, washed with water, dried over anhydrous sodium sulfate, and evaporated to dryness under reduced pressure. The viscous residue is dissolved in a mixture of 80 parts of isopropyl alcohol and 420 parts of ether, and this solution is treated with isopropanolic hydrogen chloride. The resulting precipitate is collected by filtration and washed with acetone to afford 17β-[N- (3-dimethylaminopropyl)formamido-1-androst-5-en-3β-ol hydrochloride. A solution of this hydrochloride in aqueous methanol is made alkaline by the addition of dilute aqueous sodium hydroxide, and the resulting colloidal precipitate is extracted with chloroform. The chloroform extracts washed with water, dried over anhydrous sodium sulfate and concentrated to dryness to afford a residue, which is crystallized from acetone, resulting in 17β-[N-(3- dimethylaminopropyl)formamido]androst-5-en-3β-ol, which displays a double melting point at about 116-118°C and 143-148°C, [α]D= -67.5° (chloroform).
To a slurry of 4 parts of LiAlH4 in 150 parts of dioxane is added dropwise with stirring, at the reflux temperature a solution of 10 parts of 17β-[N-(3- dimethylaminopropyl) formamido]androst-5-en-3β-ol in 150 parts of dioxane. This reaction mixture is heated at reflux for about 18 hours longer, and then treated dropwise successively, at the reflux temperature, with a solution of 4 parts of water in 25 parts of dioxane, 3 parts of 20% aqueous sodium hydroxide, and 14 parts of water. The resulting mixture is clarified by filtration, and the residue on the filter is washed with fresh dioxane. The filtrates are combined, evaporated to dryness under reduced pressure, and the resulting residue is recrystallized from acetone-methanol to produce 17β-[N-methyl-N-(3- dimethylaminopropyl)amino]androst-5-en-3β-ol, M.P. about 146-148°C, [α]D= -54.5° (chloroform). A solution of this amine in ether-isopropyl alcohol is treated with isopropanolic hydrogen chloride to afford Azacosterol dihydrochloride, [α]D= -32° (methanol).

Therapeutic Function

Hypocholesteremic

Safety Profile

Poison by ingestion andintraperitoneal routes. Experimental reproductive effects.Mutation data reported. When heated to decomposition itemits toxic fumes of NOx and HCl.

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