4-arylpiperidines, their acid addition salts, and processes for the preparation thereof

Novel compounds of Formula I wherein R1, R2, R3 and R4 are each selected from hydrogen, chloro, bromo, iodo, fluoro, trifluoromethyl, amino, nitro, lower alkyl, lower alkoxy, hydroxy, phenyl, phenoxy, benzyl, mono- or di-lower alkyl-amino, lower alkanoylamino, lower alkylthio, sulphamyl, lower alkanoyl, lower alkylsulphonyl, cycloalkyl radicals having 5-7 carbon atoms, or cycloalkyloxy radicals having 5-7 carbon atoms, or R1 and R2 and/or R3 and R4 when taken together are methylenedioxy, Y is a lower alkylene radical, and Ar is a radical of formula wherein n is from 1 to 6, and the pharmaceutically accetable non-toxic acid addition salts thereof, e.g. with penicillins, are prepared (1) by heating at 50-100 DEG C., in a suitable medium and in the presence of a base, a compound of formula A-Y-CO-NH-Ar where A is chloro, bromo, iodo or tosyloxy, with a substantially equimolar amount of a piperidine of Formula IV (2) by reacting at 50-100 DEG C., in a suitable medium and in the presence of a base, a piperidine of Formula IV above with a substantially equimolar amount of an acrylic acid amide of formula HCR5 = CR6-CONHAr where R5 and R6 are each hydrogen or lower alkyl and together contain not more than 6 carbon atoms (this process is applicable only to the preparation of those compounds in which Y separates N from CO by two carbon atoms), or (3) by reacting at 50-100 DEG C., in a suitable medium and in the presence of a base, a piperidine of Formula IV with a substantially equimolar amount of a compound of formula A-Y-COOR7 where R7 is methyl, ethyl, p-nitrophenyl or cyanomethyl, or -OR7 is chloro or bromo, and reacting the compound N-substituted with a group of formula -Y-COOR7 thus obtained, with an amine of formula H2NAr. The starting materials of formula A-Y-CONH-Ar are obtained by reacting an amine NH2-Ar with a substantially equimolar amount of a halo- or tosyloxy-acid chloride of formula A-Y-COCl. Therapeutic compositions having anti-arrhythmic activity, which may be administered orally or parenterally, contain as active ingredient a compound of Formula I above or a pharmaceutically acceptable non-toxic acid addition salt thereof.