Patent GB-869575-A (GB)
Title: Pharmaceutical compositions comprising benzylhydrazine derivatives
Inventor: SPINKS ALFRED
IPC: A61K31/15
Filed: 1958-05-02
Abstract: Benzylhydrazine derivatives of general formula:  <FORM:0869575/IV (b)/1> wherein R, R1 and R2, which may be the same or different, may be hydrogen or alkyl, alkenyl or aralkyl radicals optionally substituted e.g. by halogen atoms or alkoxy radicals and the benzene ring (A) may be optionally substituted by halogen atoms or by alkoxy or alkyl radicals, may be prepared by: (a) interaction of the corresponding benzyl halide and hydrazine; (b) partial reduction of the corresponding azine followed by hydrolysis of the benzylhydrazone; (c) complete reducttion of the said azine; (d) by reduction of the nitroso derivatives of secondary benzylamines or dibenzylamines; (e) reduction of hydrazones formed by interaction of benzylhydrazines and aldehydes or ketones; (f) interaction of chloramine and substituted benzylamines; (g) hydrolysis and decarboxylation of 1-benzyl-1,2-di-(alkoxycarbonyl)-hydrazines. Specific examples relate to: (i) the preparation of 1,1-di-(41-chlorobenzyl)-hydrazines (as the hydrochloride) by method (a) above from 4-chlorobenzyl chloride and hydrazine hydrate; (ii) the preparation of 4-chlorobenzylhydrazine (hydrochloride) by method (b) above by the reduction of 4-chlorobenzalazine with lithium aluminium hydride; (iii) the preparation of 1-benzyl-2-(41-chlorobenzyl)-hydrazine by method (c) above by reacting together benzyl hydrazine hydrochloride and 4-chlorobenzaldehyde in the presence of alkali followed by reduction of the 1-benzyl-2-(41-chlorobenzylidene)-hydrazine with sodium amalgam.ALSO:Therapeutic compositions comprise non-toxic pharmaceutical excipients in admixture with one or more benzyl hydrazine derivatives of general formula <FORM:0869575/VI/1> wherein R, R1, R2, which may be the same or different, represent hydrogen or an alkyl, alkenyl or aralkyl radicals, any of which may be optionally substituted by halogen or alkoxy radicals and wherein the benzene ring (A) may optionally be substituted by halogen atoms or alkoxy or alkyl radicals and the non-toxic acid addition salts thereof, e.g. with common inorganic acids, e.g. hydrochloric, sulphuric and phosphoric acids; organic acids, e.g. acetic, maleic, lactic, tartaric, succinic and cinnamic acids; and, to form salts of low solubility in water and/or improved solubility in lipoids, with, for example, 3 : 31-dicarboxy-2 : 21-dihydroxy-1 : 11-dinaphthylmethane and acids bearing lipophilic residues, e.g. oleic acid.  Specified compounds of the above general formula are: benzylhydrazine and its hydrochloride, oleate and cinnamate; 1 : 2-di-(41-methoxybenzyl)-hydrazine and its hydrochloride (all preferred); 1 : 2-dibenzylhydrazine and its hydrochloride; 4-methoxybenzylhydrazine hydrochloride and cinnamate, the hydrochlorides of 1-benzyl-2-methylhydrazine; 1 : 1 - dibenzylhydrazine; 1 : 2 - di - (41 - chloro - benzyl) hydrazine; 1-benzyl-2-(41-chlorobenzyl) hydrazine; 1 : 1-di-(41-chlorobenzyl) hydrazine.  The compositions may be put up in orally administrable forms, e.g. tablets, pills, dispersable powders and granules which may optionally be coated, e.g. with a sweetening agent and/or a protective material to modify the distribution and absorption of the active materials in the digestive tract, powders soluble in water, semi-solid and liquid preparations, e.g. emulsions, syrups, dispersions and solutions which may be encapsulated, in compositions with foodstuffs or for admixture with foodstuffs.  They may also be put up into parenterally administrable forms, e.g. sterile aqueous solutions and suspensions, oil solutions and sterile powders which may be used for preparing such parenteral preparations.  Reserpine may optionally be present in the compositions of the invention.