N-phenylpiperazine derivatives

Abstract

The invention comprises bases of the general formula <FORM:0997166/C2/1> (wherein X represents a straight, saturated or ethylenically unsaturated C2-4 hydrocarbon chain which may be substituted by a hydroxy or oxo group on the carbon atom adjacent to the phenyl group, R1 represents a carbamoyl, mono- or di-N-alkylcarbamoyl, sulphamoyl, mono- or di-N-alkylsulphamoyl, alkylcarbonyl, alkoxycarbonyl, cyano, alkylthio, alkylsulphinyl, alkylsulphonyl, hydroxyalkyl, nitro, aminomono- or di-alkylamino, acylamido (including alkanesulphonamido), carboxy or trifluoromethylthio group, R2 represents a hydrogen atom, a nitro group or a group -NR4R5, wherein R4 and R5 are the same or different and each represent a hydrogen atom or an alkyl or hydroxyalkyl group and R5 may additionally represent a carbon-containing acyl (including alkanesulphonyl) group or a carbamoyl, mono- or di-N-alkylcarbamoyl, thiocarbamoyl, mono- or di-N-alkylthiocarbamoyl, alkoxycarbonyl, chloroalkoxycycarbonyl or alkoxycarbonylalkyl group, or R4 and R5, together with the nitrogen atom to which they are attached represent a monocyclic 5- or 6-membered heterocyclic group (e.g. a 2-oxo-oxazolidino group obtainable by the action of an alkali metal hydroxide on a b -chloroethoxy-carbonylamino group), and R3 represents a hydrogen atom or an alkoxy group) and their toxic acid addition salts, and pharmaceutical compositions containing these compounds in association with a pharmaceutically acceptable carrier, and the preparation of the bases by (a) reacting an N-phenylpiperazine of the general formula <FORM:0997166/C2/2> with a compound of the general formula <FORM:0997166/C2/3> (wherein Y represents the acid residue of a reactive ester), or (when X is -CH2CH2- or -CH2-CH = CH-CH2- and R2 is NO2) with a nitrostyrene or nitrobutadiene of the general formula <FORM:0997166/C2/4> (wherein n=0 or 1), or (b) interaction of compounds of the general formulae <FORM:0997166/C2/5> and <FORM:0997166/C2/6> (wherein one of the symbols Z1 and Z2 represents a hydrogen atom and the other a group -CH2CH2-Y), or (c) (when X contains a CH2 group adjacent to the nitrogen atom of the piperazine nucleus) reducing a nitrile of the general formula <FORM:0997166/C2/7> (wherein B is-CH2-, -(CH2)2- or -(CH2)3-or such a grouping substituted by a hydroxy or oxo group on the carbon atom adjacent to the phenyl group) in the presence of an equimolecular proportion of an N-phenylpiperazine of the second general formula above, and in all cases, if desired, subsequently replacing either or both or R1 and R2 by a different group within the definitions thereof (e.g. reducing NO2 to NH2, alkylating, hydroxyalkylating, or acylating the latter, hydrolysing an acylamido group or reducing it to alkylamino, or hydrolysing -CN to -COOH). Starting materials are prepared as follows: m - (N,N - Dimethylsulphamoyl) - N,N - di-(b - bromoethyl) - aniline by condensing m-nitrobenzenesulphonyl chloride with dimethylamine to form m-N,N-dimethylsulphamoylnitrobenzene, reducing this to m-N,N-dimethylsulphamoylaniline. reacting this with ethylene oxide, and treating the resulting m-(N,N-dimethylsulphamoyl) - N,N - di - (b - hydroxyethyl)-aniline with phosphorus tribromide. m - N,N - Di - (b - chloroethyl) - aminoacetophenone by reacting m-aminoacetophenone with ethylene oxide and treating the resulting m-N,N - di - (b - hydroxyethyl) - aminoacetophenone with phosphorus oxychloride. N,N - Di - (b - chloroethyl) - p - nitrophenylethylamine hydrochloride by condensing p-nitrophenethyl bromide with diethanolamine and treating the resulting N,N-di-(b -hydroxyethyl) - p - nitrophenylethylamine with thionyl chloride. 1 - (m - Methylsulphonylphenyl) - piperazine by heating m-methylsulphonylaniline with diethanolamine and concentrated hydrochloric acid. The pharmaceutical compositions, which are suitable for the treatment of psychiatric disorders, may be in forms suitable for oral or parenteral administration, e.g. tablets, pills, dispersable powders, granules, emulsions, solutions, suspensions, syrups, elixirs and capsules.

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Cited By (2)

    Publication numberPublication dateAssigneeTitle
    US-4413006-ANovember 01, 1983Tanabe Seiyaku Co., Ltd.N-Aryl-N-phenoxy-alkyl-piperazine compounds useful in decreasing intracranial pressure
    US-4797401-AJanuary 10, 1989Pfizer Inc.4-Substituted-1-(4-alkylsulphonamidophenyl)piperazines as antiarrhythmic agents