Patent GB-979551-A (GB)
Title: Hydrazinium compounds and compositions containing them
Inventor: HODSON HAROLD FRANCIS
Filed: 1960-02-29
Abstract: The invention comprises quaternary hydrazinium compounds containing a cation of the formula <FORM:0979551/C1/1> (wherein R1 is hydrogen, C1- 4 alkoxy, C2- 5 alkoxycarbonyl, phenoxy or benzoyl; L and M are hydrogen, halogen, methyl or methoxy; A is ethylene, propylene, or trimethylene; and R2 and R3 are C1- 4 alkyl) but excludes 1, 1-diethyl-1-(2-phenoxypropyl)-hydrazinium chloride and 1, 1 - dimethyl - 1 - (2 - 41- methylphenoxyethyl)-hydrazinium chloride, lactate and aspirin salt. The invention also comprises the preparation of these quaternary compounds by reacting a compound of the formula R5R6R7N with a compound of the formula R8Q1 wherein R5, R6, R7 and R8 are each as appropriate, and not as respective, a phenoxyalkyl, an R2, an R3 and an amino group, and Q1 is a reactive atom or group.  Suitable anions are halides, methylsulphate, sulphate and p-toluenesulphonate, and suitable reactants for use in the process are 1, 1-disubstituted hydrazines and phenoxyalkyl halides or sulphonates, or tertiary phenoxyalkylamines and haloamines, sulphonylhydroxylamines or acylamines, or N-phenoxyalkyl-N-R2-hydrazines (which may be formed in situ from N-phenoxyalkylhydrazines and compounds R2Q2 wherein O2 is a halogen or sulphonic ester group) and compounds R3Q2. Anions may be exchanged by metathesis.  Examples are given, some products being isolated as picrates and then converted to other salts.  In the Provisional Specification R1 is additionally defined as C1- 6\t alkoxy, acetyl, propionyl, isobutyryl, acetamido, propionamido, substituted phenoxy and substituted benzoyl (the substituents being halogen, alkyl, alkoxy, nitro, amino and acylamino): the benzene ring may be substituted in any of the free positions by halogen, methyl, methoxy, ethyl, hydroxy or nitro; and R2 and R3 are additionally defined as hydroxyalkyl and alkenyl or NR2R3 may be a pyrrolidino, piperidino or morpholino group.ALSO:Pharmaceutical compositions contain quaternary hydrazinium compounds containing a cation of the formula <FORM:0979551/A5-A6/1> (wherein R1 is hydrogen, C1-4 alkoxy, C2-5 alkoxycarbonyl, phenoxy or benzoyl; L and M are hydrogen, halogen, methyl or methoxy; A is ethylene, propylene or trimethylene; and R2 and R3 are C1-4 alkyl) or 1,1-dimethyl-1-(2 - 41 - methylphenoxyethyl) - hydrazinium chloride, lactate or aspirin salt and a carrier.  They have a sympatholytic action, and may take the form of powders or granules which may contain dispersing and surface-active agents and may be presented in a draught in water or in a syrup; as capsules or cachets in a dry state or in a non-aqueous suspension, when a suspending agent may be added; in suspension in water, a syrup or an oil, or an oil/water emulsion, when flavouring, preserving, suspending, thickening and emulsifying agents may be included; in aqueous injection solutions which may contain antioxidants, buffers, bacteriostats, solubilizing agents, and solutes for rendering the compound isotonic; in nonaqueous solutions or suspensions; or as pills, tablets, suppositories or pessaries. Tablets and aqueous solutions containing 1-(2-21,61-dimethylphenoxyethyl) - 1,1 - dimethylhydrazinium chloride as described.  Other anions referred to are the bromide, iodide, sulphate, methylsulphate and p-toluenesulphonate anions.  In the Provisional Specification R1 is additionally defined as C1-6-alkoxy, acetyl, propionyl, isobutyryl, acetamido, propionamido, substituted phenoxy and substituted benzoyl; the benzene ring may be substituted in any of the free positions by halogen, methyl, methoxy, ethyl, hydroxy or nitro; and R2 and R3 are additionally defined as hydroxyalkyl and alkenyl, or NR2R3 may be a pyrrolidino, piperidino or morpholino group.