GB1056421A - Carboxylic acid piperazides and process for their manufacture - Google Patents

Abstract

The invention provides carboxylic acid piperazides of the general Formula I <FORM:1056421/C2/1> wherein R represents the radicals of the general Formulae II or III <FORM:1056421/C2/2> <FORM:1056421/C2/3> wherein R2 represents hydrogen or a phenyl radical which may be substituted by a halogen atom, R3 and R4 each represents a phenyl or benzyl radical which may be substituted by one or more halogen atoms and the benzyl radical, if desired, may be substituted in alpha-position by a methyl or ethyl radical, or R2 and R3 together may represent a benzylidene radical which may be substituted by one or more halogen atoms, R5 and R6 each represents a phenyl radical which may be substituted by one or more halogen atoms, alkyl or alkoxy radicals containing 1 or 2 carbon atoms or halogen substituted phenoxy radical, and R7 represents a methyl radical or a 2-phenyl-vinyl radical which may be substituted in the benzene nucleus by one or more halogen atoms, and R1 represents hydrogen, a branched or unbranched alkyl radical containing 1 to 12 carbon atoms which may be substituted by hydroxy groups, alkoxy groups containing 1 to 4 carbon atoms or dialkylamino groups having 1 or 2 carbon atoms in each alkyl group; furthermore a cycloalkyl radical containing 5 to 8 carbon atoms or a phenylalkyl radical having 1 or 2 carbon atoms in the alkylene portion, and n = 0 or 1, with the proviso that when R in the general Formula (I) represents a group of the general Formula (II) given above, n must not equal 0 when R1 is an alkyl radical having 1 to 4 carbon atoms, R2 is hydrogen and R3 and R4 are halogen-substituted phenyl radicals, and acid addition salts of the above-mentioned compounds. The invention further provides a process for the production of carboxylic acid piperazides corresponding to the general Formula (I) above wherein R and R1 have the meanings given above, which comprises reacting in known manner a carboxylic acid of the general Formula (IV) R-COOH wherein R has the meaning given above, or a reactive derivative thereof, with a piperazine of the general Formula (V) <FORM:1056421/C2/4> wherein R1 has the meaning given above, and, if necessary, catalytically hydrogenating and/or alkylating the reaction products and, if necessary, converting them into the corresponding salts by treating them with physiologically tolerated acids. The carboxylic acids of the general formula <FORM:1056421/C2/5> that are used as starting products in the process of the invention are at least disubstituted by phenyl and/or benzyl radicals and may carry, in the nucleus, one or more halogen atoms and at the alpha-carbon atom of the benzyl radicals, alkyl groups of low molecular weight wherein R2, R3 and R4 have the above meanings. Any halogen, especially chlorine, may be present as substitutent in the above-mentioned reactants. The carboxylic acids of the above general Formula (VI) may be obtained by known processes, for example from their nitriles (prepared, for example, according to Specifications 897,693, 921,979 and 938,732) by hydrolysis. The substituted alpha, beta-diphenyl-acrylic acids used, inter alia, as starting substances are advantageously prepared by condensation of corresponding benzaldehydes with molar amounts of triethylamine salts of corresponding phenyl-acetic acids in boiling acetic acid anhydride. From these unsaturated acids, the alpha-beta-diphenyl-propionic acids may be obtained by catalytic hydrogenation in the presence of Raney nickel as a catalyst, and using methanol as solvent. The carboxylic acids of the general Formula (VII) <FORM:1056421/C2/6> that can also be used as starting substances, according to the invention, are substituted at the carbon atom 5 by phenyl radicals, which, in the nucleus, may carry one or more halogen atoms, alkyl or alkoxy radicals which contain 1 to 4 carbon atoms and/or a phenyloxy group which may be substituted by halogen. Likewise, the 2-phenyl-vinyl radical which may be present in 2-position of the carboxylic acid corresponding to the general Formula (VII), may be substituted in the benzene nucleus by one or more halogen atoms or by alkyl- and/or alkoxy groups which contain 1 to 4 carbon atoms. Pharmaceutical compositions comprise a compound of the first general formula above together with a suitable auxiliary carrier substance in conventional form for oral or parenteral administration. They have anthelmintic properties which are disclosed.