Patent GB-919491-A (GB)
Title: Pharmaceutical compositions
Inventor: CROWTHER ALBERT FREDERICK
IPC: A61K47/48
Filed: 1958-12-23
Abstract: The invention comprises inter alia salts of a -methylbenzylhydrazine with acidic synthetic resins, e.g. sulphonated polystyrene resins. They may be made by interaction of a salt (e.g. the sulphate or oxalate) of the base with the resin in an aqueous medium.  Reference is also made to salts with other benzylhydrazine derivatives covered by the general formula <FORM:0919491/IV(a)/1> wherein R represents a C1-4 alkyl radical, R1 hydrogen or a methyl radical, R2 hydrogen, an alkyl or alkoxycarbonyl radical and R3 hydrogen, an alkyl or aralkyl radical, or a radical COR1 wherein R1 represents hydrogen or an alkyl, alkoxy, aryl or aralkyl radical, and wherein the ring A may bear further substituents.ALSO:The invention comprises: (a) compounds of the general formula <FORM:0919491/IV (b)/1> (wherein R represents a C1-4 alkyl radical, R11 represents hydrogen or an alkyl, alkoxy, phenyl or aralkyl radical, and the ring A may optionally bear further substituents) and their non-toxic acid addition salts; (b) salts of a -methylbenzylhydrazine with tannic acid and with acidic synthetic resins; (c) the preparation of compounds (a) by reducing hydrazones of the general formula <FORM:0919491/IV (b)/2> or by reacting compounds of the general formula <FORM:0919491/IV (b)/3> with an acylating agent derived from an acid R11COOH; and (d) pharmaceutical compositions containing the foregoing and related compounds (see Group VI).  Certain of the last mentioned compounds, which are isolated and used in the form of their oxalates, are prepared as follows:-  4-Chloro-a -methylbenzylhydrazine by heating 4-chloro-1-ethylbenzene with diethyl azodicarboxylate, and hydrolysing and decarboxylating the resulting 1 - (41 - chloro-a -methylbenzyl)-1,2-diethoxycarbonylhydrazine; a ,4-dimethyl-, 4-methoxy-a -methyl-, a -ethyl-, 4-benzyloxy-a -methyl- and 4-ethyl-a -methyl-benzylhydrazine analogously.  31,41-Dichloro-a -methylbenzylhydrazine by hydrolysing and decarboxylating 1-(31,41-dichloro - a  - methylbenzyl) - 2 - ethoxycarbonyl-hydrazine.  a -Methyl-4-n-propylbenzylhydrazine by condensing 4-n-propylacetophenone with acetylhydrazine, catalytically hydrogenating the resulting hydrazone, and hydrolysing the product. 1 - (a  - Methylbenzyl)-1-methylhydrazine by treating a  - methylbenzylmethylamine with nitrous acid and reducing the resulting nitrosamine.  1-(a ,41-Dimethylbenzyl)-2-methylhydrazine by reducing 1 - (a ,41 - dimethylbenzyl) - 2 - ethoxy-carbonylhydrazine. According to the second Provisional Specification, the nitrogen atom carrying the group -COR11 may additionally carry an alkyl, alkenyl, cycloalkyl or aralkyl radical, whilst R may additionally represent an aryl radical.ALSO:Pharmaceutical compositions for oral or parenteral administration as antidepressant, stimulant, anticonvulsant, sedative and/or antirheumatic agents comprise, in admixture with non-toxic pharmaceutical excipients, one or more benzylhydrazine derivatives of the general formula <FORM:0919491/VI/1> (wherein R represents a C1-4 alkyl radical, R1 hydrogen or a methyl radical, R2 hydrogen or an alkyl or alkoxycarbonyl radical and R3 hydrogen, an alkyl or aralkyl radical, or a radical COR1 wherein R1 represents hydrogen or an alkyl, alkoxy, aryl or aralkyl radical, and wherein the ring A may bear further substituents) or their non-toxic pharmaceutically acceptable acid addition salts (solutions of 1,2-bis - (a  - methylbenzyl) - hydrazine in n-heptane and solutions or suspensions of a -methylbenzylhydrazine in water, alcohol, methanolic potassium hydroxide, aqueous hydrochloric acid, methylene dichloride, benzene/cyclohexane, ether, ethyl acetate or benzene being disclaimed).  Specified salts include those with acidic synthetic resins, and tannates.  The compositions may also contain other therapeutic agents, e.g. reserpine.  Examples are given of injection solutions and suspensions, tablets, capsules and emulsions, and reference is also made to pills, dispersible powders, granules, syrups and foodstuffs or additives thereto.  According to the Provisional Specifications, R may additionally represent an aryl radical, R1 may represent any alkyl radical and additionally an aryl radical, R2 may additionally represent an alkenyl, cycloalkyl, aralkyl or acyl radical, optionally substituted, R3 may additionally represent an alkenyl, cycloalkyl or acyl radical, optionally substituted, and the nitrogen atom carrying R3 may also carry an alkyl, alkenyl, cycloalkyl or aralkyl radical, optionally substituted, or may form part of a heterocyclic ring.