Patent GB-834913-A (GB)
Title: Steroids and biologically active preparations containing steroids
IPC: C07J5/00
Filed: 1956-11-29
Abstract: The invention comprises 3-acid polycarboxylic esters of pregnanes and allopregnanes of the general formula <FORM:0834913/IV (b)/1> wherein Y represents an oxo or 11b -hydroxy group and the polycarboxylic acids contain 2 to 8 carbon atoms and the preparation of the salts by reacting free 3-hydroxy-substituted pregnanes or allopregnanes with the polycarboxylic acids or anhydrides thereof and converting the resulting acid esters into alkali metal, ammonium or substituted ammonium salts.  The esters may be derived from malonic, adipic, succinic, glutaric, pimelic, fumaric, maleic, malic, tartaric, citric, aconitic, tricarballylic, aspartic, suberic, glutamic or phthalic acid.  A preferred acid is an aliphatic dicarboxylic acid having from 2 to 8 carbon atoms.  The esters may be prepared by reacting an excess of the required acid anhydride with the pregnane or allopregnane preferably in the presence of pyridine.  The salts may be prepared by reacting the 3-acid polycarboxylic ester with the required base such as sodium bicarbonate or sodium hydroxide, in aqueous solution.  Suitable salts mentioned are the ammonium, potassium and sodium salts and salts derived from dimethylamine, trimethylamine, diethylamine, triethylamine, diethanolamine, dimethylethanolamine, dimethylbenzylamine, N : N1-tetramethyl - hexamethylene - diamine, procaine and "Xylocaine" (Registered Trade Mark) and other amines containing alkyl, aryl and/or aralkyl groups. A number of detailed examples are given in which the steroid reactants are 3a  (and 3b -dihydroxy-20-oxo-pregnane, 3a  - hydroxy - 11,20 - dioxo - pregnane and allopregnane, and 3b  - hydroxy - 11,20-dioxo-allopregnane.  The Specification also refers to 3-esters of compounds of the above general formula derived from monocarboxylic acids containing from 1 to 10 carbon atoms, e.g. derived from aliphatic, aromatic and araliphatic carboxylic acids, a large number of which are detailed.ALSO:A therapeutic preparation suitable for oral or parenteral administration contains as the active ingredient a pregnane or allopregnane of the general formula <FORM:0834913/VI/1> wherein X represents an oxo or an a - or b -hydroxy group, or an a - or b -acyloxy group derived from a monocarboxylic acid containing from 1 to 10 carbon atoms or a 3-acid ester thereof derived from a polycarboxylic acid containing from 2 to 8 carbon atoms or an alkali metal, ammonium or substituted ammonium salt of said polycarboxylic ester and Y represents an oxo or b -hydroxy group.  Thus any of the following steroid compounds may be incorporated in the composition: 3,11,20-trioxopregnane and allopregnane, 3a -hydroxy-11,20-dioxo - pregnane and allopregnane, 3b  - hydroxy - 11,20 - dioxo - allopregnane, and 3a  (and 3b ), 11b -dihydroxy-20-oxo-pregnane, and the 3-esters thereof-particularly those derived from formic, acetic, propionic, butyric, valeric, capronic, venanthic, caprylic, crotonic, b -cyclopentylpropionic, g  - cyclohexylbutyric, chloracetic, trifluoro - acetic, trimethyl - acetic, diethyl - acetic, carbamic, glycine, alanine, serine, leucine, benzoic, phenyl-acetic, b -phenylpropionic, furane-2-carboxylic acid and isonicotinic acid; and the dicarboxylic acids such as malonic, succinic, glutaric, pimelic, fumaric, maleic, malic, tartaric, citric, aconitic, tricarballylic, aspartic, glutamic and phthalic acids.  The salts of the 3-acid esters may be a sodium, potassium, dimethylamine, trimethylamine, diethylamine, triethylamine, diethanolamine, dimethylethanolamine, dimethylbenzylamine, N,N1 - tetramethyl - hexamethylene-diamine, procaine or "Xylocaine" (Registered Trade Mark).  Suitable diluents are water, sodium chloride, glucose, lactose, starch, talc, magnesium stearate, benzyl alcohol, arachis oil, polyoxyethylene - sorbitan - monolaurate, carboxymethylcellulose, and sodium phosphates.