Patent GB-970597-A (GB)
Title: Therapeutic compositions containing n-substituted 4-aralkyl-piperidines
IPC: A61K31/445
Filed: 1963-01-14
Abstract: N-Substituted 4-aralkyl-piperidines of general formula <FORM:0970597/C1/1> wherein Alk represents an alkylene bridge containing 1 to 3 carbon atoms, Alk1 represents an alkylene bridge containing 2 or 3 carbon atoms, R and R1 represent the same or different lower alkyl groups or R and R1 together with the adjacent nitrogen atom form a pyrrolidine, piperidine or morpholine ring system, x represents a substituent not adversely affecting the pharmacological properties of the compounds (see Division A5), y represents lower alkyl, n is an integer from 0 to 3, and m is an integer from 0 to 2, are prepared by reacting a 4-phenylalkylpiperidine of general formula <FORM:0970597/C1/2> with a dialkylaminoalkyl halide or sulphonate of general formula <FORM:0970597/C1/3> wherein Alk, Alk1, R, R1, x, y, m and n have the meanings given above and X represents chlorine, bromine or iodine, or R11SO3-where R11 is a hydrocarbyl radical. The substituent x in the piperidine derivatives may be halogen, lower alkyl, lower alkoxy, methylene-dioxy (equivalent to two substituents), amino, nitro, trihalomethyl, hydroxy, mercapto or lower alkylthio.  (The terms "lower alkyl" and "lower alkoxy" used herein refer to straight or branched chain alkyl or alkoxy radicals having 1 to 4 carbon atoms). The N-substituted 4-aralkyl-piperidines can be reacted with both inorganic and organic acids to form acid addition salts. Specification 842,995 is referred to.ALSO:Therapeutic compositions in the form of tablets, capsules or aqueous, parenteral solutions or suspensions comprise as active ingredient a N-substituted 4-aralkyl-piperidine of the general formula <FORM:0970597/A5-A6/1> wherein Alk represents an alkylene bridge containing 1 to 3 carbon atoms, Alk1 represents an alkylene bridge containing 2 or 3 carbon atoms, R and R1 represent the same or different lower alkyl groups or R and R1 together with the adjacent nitrogen atom form a pyrrolidine, piperidine or morpholine ring system, X represents a substituent not adversely affecting the pharmacological properties of the compound, y represents a lower alkyl group, n is an integer from 0 to 3, and m is an integer from 0 to 2, or a pharmaceutically acceptable acid addition salt thereof.  (The terms "lower alkyl" and "lower alkoxy" used herein refer to straight or branched chain alkyl or alkoxy radicals having 1 to 4 carbon atoms.)  The substituent x may be halogen, lower alkyl, lower alkoxy, methylenedioxy p  (equivalent to two substituents), amino, nitro, trihalometryl, hydroxy, mercapto or lower alkylthio.  The acid addition salts may be those of hydrochloric, hydrobromic, hydriodic, sulphuric, phosphoric, acetic, tannic, citric, malic, ethane-sulphonic and cyclohexylsulphamic acids.  Active ingredients specified are 4 - benzyl - 1 - (b  - dimethylaminoethyl) - piperidine and its dihydrochloride, 4-benzyl-1-(b -diethylaminoethyl) - piperidine dihydrochloride, 4 - benzyl - 1 - (g  - dimethylaminopropyl) - piperidine dihydrochloride, 4 - phenethyl - 1 - (b  - dimethylaminoethyl) - piperidine dihydrochloride, 4 - p - chlorophenethyl - 1 - (b  - diisopropylaminoethyl) - piperidine, 4 - (3,4 - methylenedioxy phenethyl) - 1 - (g  - piperidino propyl)-piperidine, 4 - (3,4,5 - trimethoxy phenethyl) - 3 - ethyl - 1 - (b  - diethylaminoethyl) - piperidine, 4 - (g  - phenylpropyl) - 1 - (g  - pyrrolidinopropyl) - piperidine, 4 - (b  - phenylpropyl) - 1 - (b  - diethylaminopropyl) - piperidine and 4 - phenethyl - 1 - (b  - piperidinopropyl) - piperidine.  The active ingredients exert an antiatherosclerotic effect and potentiate the antihypertensive action of Veratrum alkaloids, e.g. cryptenamine. (For the preparation of the active ingredients see Division C2.) Specification 842,995 is referred to.