GB753793A - Aryloxy esters of testosterone, and therapeutic compositions thereof - Google Patents

Abstract

The invention comprises testosterone esters of the general formula <FORM:0753793/IV(a)/1> where R is an aryl radical or a lower alkyl, alkoxy or halogen substitution product thereof, X is H or lower alkyl (1-6 carbon atoms) and n is 0, 1 or 2; and a process for their preparation by esterifying testosterone by a method normally used for esterifying hydroxylated steroids. Specified methods are (1) treatment of testosterone with (a) the appropriate acid halide or anhydride, preferably in an inert solvent, e.g. benzene, tetrahydrofuran, and using an acid-binding agent, e.g. pyridine; (b) the appropriate free acid in an inert solvent, e.g. toluene, and using an acid catalyst, e.g. p-toluene sulphonic acid; (2) reaction of a 17-halogenated derivative of testosterone with the silver salt of the appropriate phenoxy acid. In examples: (1) testosterone is refluxed with phenoxyacetic anhydride in benzene to yield testosterone phenoxyacetate; (2) testosterone in tetrahydrofuran is refluxed with p-chlorophenoxyacetyl chloride to yield testosterone p-chlorophenoxyacetate. Similarly, using the appropriate acid chlorides, testosterone 2 : 4-dichlorophenoxyacetate, a - phenoxybutyrate and b -phenoxypropionate are prepared. Other esters listed are the p-methyl-, p-bromo-, p-methoxy-, o-chloro- and p-tert-butyl-phenoxyacetates, and the (-) and (+)-a -phenoxypropionates.ALSO:Pharmaceutical compositions for androgenic therapy comprises an androgenic agent consisting essentially of a testosterone ester of the general formula: <FORM:0753793/VI/1> (wherein R is an aryl radical or a lower alkyl, alkoxy or halogen substitution product thereof, X is H or lower alkyl, and n is O, 1 or 2) together with a non-toxic vehicle. The esters may be formulated as an injectable suspension a) in aqueous media, incorporating a wetting agent; (b) in an anhydrous hydrophilic base e.g. polyethylene glycol; or (c) in an oleaginous vehicle, e.g. sesame oil containing aluminium monostearate and propyl paraben. A typical aqueous injectable suspension incorporates dibasic sodium phosphate, monobasic potassium phosphate, polysorbate 80, sorbitan monolaurate, and thimerosal in addition to testosterone phenoxyacetates. The esters may also be administered as ointments, tablets or suppositories, specified diluents being cetyl alcohol, glyceryl laurate, glyceryl monostearate, magnesium stearate, glycerine, propyl paraben, begamot, starch, gelatin, lactose, ol. theobroma, and alcohol.