Patent GB-1071120-A (GB)
Title: Pharmaceutical compositions containing substituted aralkyl amines
IPC: A61K31/135
Filed: 1965-10-26
Abstract: Compounds of the formula <FORM:1071120/C2/1> wherein R is a C1 to C3 straight chain alkylene group, i.e. allyl substituted benzyl-, phenethyl-, or phenylpropyl-amines, in the latter two of which the allyl group may be in the a - or b -position, are prepared by one of the following processes:  (1) a -allyl derivatives are prepared by Hoffman degradation of the amide containing one carbon atom more than the required derivative; the reaction may be effected by dissolving the amide in cold aqueous hypohalite, followed by warming the solution; (2) a -allyl derivatives are prepared by a modification of (1), wherein the reaction is effected in methanol to give the intermediate methylcarbamate derivative, which is then hydrolysed with alkali to the required a -allyl compound; (3) b -allyl derivatives are prepared by lithium aluminium hydride reduction of the corresponding amide in an organic solvent, followed by aqueous decomposition of the organo-metallic complex to give the required product.  Examples are given for the following preparations:  (1) a -allylphenethylamine, by solution of allylbenzylacetamide in cold aqueous sodium hypobromite, followed by warming, and subsequent ether extraction of the required product; the hydrochloride, sulphate, monohydrogen citrate, and tartrate salts of this amine are also prepared; (2) b -allylphenethylamine is prepared by reduction of a -allyl-a -phenylacetamide with LiAlH4 in tetrahydrofuran, followed by aqueous decomposition of the complex to give the required amine, which is purified by distillation; the hydrochloride salt is then prepared; (3) Allyl-benzylamine is prepared from a -allyl-a -phenylacetamide, as in (1) above, and the hydrochloride then prepared; (4) b -allyl-g -phenylpropylamine from a -allyl-b -phenyl propionamide, as in (2) above, and then converted to the hydrochloride salt; (5) a -allyl-g -phenylpropylamine is prepared by aqueous alkaline hydrolysis at elevated temperature of methyl-4-(6-phenyl-1-hexenyl carbamate, the resulting amine then being converted to the hydrochloride. The compounds are used in analgesic and tranquillizing pharmaceutical compositions (see Divisions A5-A6).ALSO:Pharmaceutical compositions, for oral, parenteral and topical application, comprise an allyl-substituted benzyl-, phenethyl-, or phenyl propyl-amine, of formula: <FORM:1071120/A5-A6/1> wherein R is a straight chain alklene group having 1, 2 or 3 carbon atoms, and the allyl group may be in the a or b  position, on the alkylene chain relative to the amino group, or acceptable salts of these, with a suitable carrier.  Carriers include tartaric acid; mannital; starch; sterile water; white ointment V.S.P.; syrups and elixirs, syrups containing, in water, sodium benzoate, tartaric acid, dye, flavoring and sorbitol, and elixires being a similar solution in aqueous alcohol.  Talc and magnesium stearate are used as tabletting lubricants.  Examples are given for the preparation of tablets and parenteral solutions of a -allyl phenethyl -amine hydrochloride, and for a syrup, an elixir, and an ointment containing the corresponding b -derivative salt.  Syntheses of the active agents are also exemplified (see Division C2).  The compositions are said to possess analgesic, tranquilizing, antidepressive or anorexiant properties, according to the dosage used.