Patent GB-1056932-A (GB)
Title: New amino-steroids and processes for their preparation
IPC: C07J5/00
Filed: 1963-08-06
Abstract: The invention comprises a 21,21-bis-(amino-methyl) - 3a  - hydroxy - 5b  - or 3b  - hydroxy-5a  -pregnane of the general formula <FORM:1056932/C2/1> in which R1 is a hydrogen atom or an acyl radical derived from an organic carboxylic acid having from 1-18 carbon atoms, R2 represents two hydrogen atoms or the oxygen atom of a keto group, and R3 is an alkyl group having from 1-18 carbon atoms or a non-toxic acid addition salt thereof and a process for the preparation thereof in which a 3a  - acyloxy- or 3b  - acyloxy - 21,21 - bis - (hydroxymethyl)-5b - or 5a -pregnane starting material of the general formula <FORM:1056932/C2/2> wherein R4 is an acyl radical derived from an organic carboxylic acid having from 1-18 carbon atoms, is reacted with a functional derivative of a sulphonic acid to form the corresponding 21,21-disulphonate of the 3-acyloxy - 21,21 - bis - (hydroxymethyl) - pregnane which is reacted with an alxali metal halide to form the corresponding 3-acyloxy-21,21 -bis-(halogenmethyl)-pregnane which is condensed with either a primary or secondary amine to yield the desired corresponding 3a -acyloxy - 21,21 - bis - (aminomethyl) - 5b -pregnane or 3b  - acyloxy - 21,21 - bis - (amino-methyl) -5a -pregnane, which finally, if desired, is saponified to the corresponding 3a - or 3b -hydroxy conpound and/or salified to form a non-toxic acid addition salt.  The 3-acyloxy-21,21 -bis-(hydroxymethyl)-pregnane may be obtained by reacting a 3a - or 3b -hydroxy-21-bis -(hydroxymethyl)-5b  or 5a -pregnane of the formula <FORM:1056932/C2/3> with a lower aliphatic ketone or aldehyde or araliphatic aldehyde to form the corresponding ketonide which is then reacted with an esterifying agent to form the 3-ester and the 21,21-bis(hydroxymethyl) group regenerated.  The 3a - or 3b -hydroxy-21-bis-(hydroxymethyl)-5b  or 5a -pregnane is obtained by condensing a 3a - or 3b -hydroxy-17b -formyl-5b  or 5a -androstane (a) with a lower alkyl cyanoacetate to form a 21-cyano-21-carboalkoxy-pregn-20-ene, hydrogenating the latter to form a 21-cyano-21 -carboalkoxy pregnane, treating the latter with alkali metal base to form a 21,21-dicarboxylic acid pregnane, esterifying the latter to form a dialkyl ester of a 21,21-dicarboxylic acid pregnane, and reducing with mixed metal anhydride, or (b) with a dialkyl malonate to form a 21,21-bis-(carboalkoxy)-pregn-20-ene, hydrogenating the latter to form a 21,21-bis-(carboalkoxy)-pregnan and reducing the latter with a mixed metal hydride.  The 3-hydroxy-17b -formyl-androstane is obtained by reducing a 3a - or 3b -hydroxy or acyloxy - 21 - acyloxy-pregnan-20-one with alkali metal borohydride and saponifying to form a 3,20,21-trihydroxy pregnane, treating the latter with a per-acid in the presence of a lower alkanol to form the dialkyl ketal of a 3-hydroxy-17b -formyl androstane and hydrolysing the latter. Pharmaceutical compositions containing the above compounds and having coronarodilatory and, peripheral vasodilatory activity are administered orally as tablets, sublingual tablets, pills or other orally ingestible dosage units, or by sterile injectible solution or suspension.