ES351896A1 - Improvements in or relating to Piperazinyl Derivatives - Google Patents

Abstract

Novel aryl-substituted piperazinyl-carboxylic acid anilides having the general Formula (I) in which R 1 , R 2 and R 3 are H, alkyl of up to 5 carbon atoms inclusive, alkoxy of up to 5 carbon atoms inclusive, allyloxy, an aralkoxy or cyanoalkyl radical whose alkyl radical has up to 6 carbon atoms inclusive, or R 1 and R 2 together are -O-Alkylene-O-,A is an unbranched or branched, saturated or unsaturated divalent aliphatic radical of up to 7 carbon atoms inclusive which is unsubstituted or substituted by hydroxy, alkoxy of up to 3 carbon atoms inclusive, alkyl of up to 3 carbon atoms inclusive, aryl or aralkyl, Y is H, an alkyl radical of up to 5 carbon atoms inclusive or an aryl radical substituted by alkoxy or halogen, Z is an alkyl or alkoxy radical of up to 5 carbon atoms inclusive, halogen, nitrilo or trifluoroalkyl, and X is halogen, nitro, trifluoroalkyl, nitrilo, sulphonic acid, sulphonamido, carboxy, carbalkoxy, carboxamido, N-carboxylanilino or the 4 - carboxylamino - benzosulphonamido (1) group are prepared in a process which comprises reacting a carboxylic acid anilide of the general Formula (II) wherein R 1 , R 2 , R 3 , X and A have the meanings indicated above and Hal is halogen at a temperature from 10 to 150 C. with an aryl substituted piperazine having the general Formula (III) in which Y and Z have the meanings indicated above, in the presence or absence of an auxiliary base which does not react with either reactant, and separating the resultant aryl-substituted piperazinyl-carboxylic acid anilide. 3 - Chioropropionic acid - (2 - suiphamyl - 4,5- dimethoxy) anilide is obtained from 6-amino- 3,4-dimethoxybenzene sulphonamide and 3- chloropropionyl chloride. 6 - Amino - 3,4 - dimethoxybenzene sulphonamide is obtained by reduction of 6-nitro-3,4-dimethoxybenzenesulphonamide with Raney nickel/hydrazine hydrate in a methanol-tetrahydrofuran mixture. Intermediates of Formula (II) where X is halogen are prepared by treating the corresponding compound where X is H with sulphenyl chloride or bromine and glacial acetic acid. Intermediates of Formula (II) where X is H are prepared by treating the corresponding aniline with a halo-acid chloride. Intermediates of Formula (II) where X is a nitro group are prepared by nitration of the corresponding compound where X is H with nitric acid and glacial acetic acid. Pharmaceutical compositions having sedative, neuroleptic, anticonvulsive, analgesic, antihistaminic, antiiserotonic and bloodpressure-lowering effects and containing arylsubstituted piperazinyl-carboxylic acid anilides defined above, are administered orally, intraperitoneally, intravenously, or intramuscularly in association with a pharmaceutically acceptable carrier.