Patent GB-804521-A (GB)
Title: Improvements in or relating to steroids and the preparation thereof
IPC: C07D295/096
Filed: 1955-05-17
Abstract: The invention comprises a compound of the formula <FORM:0804521/IV (b)/1> wherein at least D and/or E is a polar group which is a salt of an acid ester of a polycarboxylic acid having the formula <FORM:0804521/IV (b)/2> in which L represents -(CH2)n, -O-(CH2)n and -NH-(CH2)n-, n being a number from 1 to 6 and M+ represents Na+, K+, NH4+ or derivatives of the ammonium ion; or wherein D and/or E is a polar group which is a salt of an amino acid ester having the formula <FORM:0804521/IV (b)/3> wherein y+ is an ammonium function substituted by H, alkyl, hydroxyalkyl, aminoalkyl, aryl or aralkyl groups, and zis a pharmacologically acceptable anion; or E may be H or hydroxy (free or esterified with non-ionic ester groups); or D may be keto, hydroxy (free or esterified with non-ionic ester groups) or an oxime (free or esterified with ionic or non-ionic ester groups); and a process for the preparation thereof which comprises reacting the corresponding non-ionic ester with a salt-forming agent. Examples describe the preparation of (1) salts of 21-hydroxypregnane-3,20-dione hemisuccinate with N,N1-tetramethyl hexamethylene diamine, dimethylaminoethanol, diethylaminoethanol, dimethylbenzylamine, trimethylamine, procaine and triethylamine; (2) 21-hydroxypregnane-3,20-dione sodium hemisuccinate; (3) 21 - hydroxypregnane - 3,20 - dione dimethylamino acetate methochloride; (4) 3a ,21-dihydroxypregnane - 20 - one - 21 - hemisuccinate; (5) 3a ,21 - dihydroxypregnane - 20 - one - 21-acetate, the 3-hemisuccinate thereof and the 3 - diethylaminoacetate ethochloride; (6) pregnane - 3b  - ol - 20 - one - 3 - hemisuccinate; (7) the 3-hemi-succinate of pregnanedione-3-oxime; (8) 21 - hydroxypregnane - 3,20-dione - b  - dimethylaminoethyl carbonate; (9) 21 - hydroxypregnane - 3,20 - dione - b  - diethyl-aminoethyl carbamate; (10) the sodium salt of RO.CO.O.CH2.COOH, where R is 21-hydroxypregnane - 3,20 - dione; (11) the sodium salt of R-O-CO-NH-CH2-COOH; (12) 21-hydroxypregnane - 3,20 - dione diethylamino acetate hydrochloride; (13) 21-hydroxypregnane - 3,20 - dione - piperidinoacetate hydrochloride; (14) 21 - hydroxypregnane - 3,20-dione diethylaminoacetate methobromide; (15) 21 - hydroxyallopregnane - 3,20 - dione sodium hemisuccinate; (16) 3b -hydroxyallopregnane-20-one sodium succinate; (17) pregnane-3a -ol-20-one-3-hemisuccinate.  Specifications 804,522 and 804,523 are referred to.ALSO:Salts of acid esters derived from 21-hydroxypregnane - 3,20 - dione and its allo - isomer (see Group IV (b)) are useful as anaesthetic, anti-convulsant, sedative, analgesic and hypnotic agents and may be employed orally, subcutaneously and intramuscularly.  In aqueous solution, saline or glucose is added to obtain an isotonic solution.  Tablets for oral administration contain a tablet forming material such as starch.  Elixirs and suspensions in a carrier can also be administered orally.  Among many compounds mentioned are 21-hydroxy-pregnane-3,20-dione diethylaminoacetate hydrochloride, 21 - hydroxy - pregnane - 3,20 - dione sodium hemisuccinate, the triethylamine salt of 21 - hydroxypregnane - 3,20 - dione hemisuccinate and pregnane 3a -ol-20-one-3-sodium hemisuccinate, and the corresponding allopregnane compounds.  Specifications 804,522 and 804,523, [both in Group IV (b)], are referred to.