GB1013904A - Piperazinium salts and compositions containing them - Google Patents

Abstract

The invention comprises pharmaceutically acceptable salts of piperazinium cations of the formula <FORM:1013904/C2/1> or a pharmaceutically acceptable acid addition salt thereof, wherein A represents a straight or branched saturated alkylene chain of 2 to 6 carbon atoms; B represents a group of the formula <FORM:1013904/C2/2> or <FORM:1013904/C2/3> or <FORM:1013904/C2/4> wherein R1 and R2 are the same or different (except that R1 and R2 may not both represent thienyl, naphthyl, phenyl or phenoxyethyl groups) and each represents an alkyl group of 1 to 10 carbon atoms, or a thienyl, naphthyl, phenyl or phenoxyethyl group, optionally attached to the nitrogen atom via a straight or branched saturated alkylene chain of 1 to 5 carbon atoms and optionally carrying in the phenyl ring one or more halogen, methoxy, acetamido or amino substituents; and R3 represents a methyl, ethyl, propyl or benzyl group, and the preparation thereof by reaction of a 9-substituted acridine, wherein the substituent is a reactive hydrogen-accepting atom or group, with a salt of a cation of the formula H2N.A.B; by reaction of a 9-(o -X-alkylamino) acridine or a 9 - (o - X - alkylacylamino) acridine, wherein X is a proton accepting group or atom with a compound of the formula <FORM:1013904/C2/5> or <FORM:1013904/C2/6> and hydrolysing the product to the desired piperazinium cation where a 9-(o -X-alkylocylamino) acridine is used as starting material or by reaction of a 9-[o -(4-R1-piperazin-1-yl)-alkylamino] acridine, a salt of a 4-[o -(acridin- 9 - ylamino) alkyl] - 1 - R1 - 1 - R2 - piperazinium cation or a 4-[o -acridin-9-ylamino)-alkyl]-4-R3-1-R1-piperazinium cation with a quaternizing derivative of the remaining group. When the quaternizing group contains an amino group, said group may be protected by converting it into an acyl derivative, followed by hydrolysing to give the free amino group. N-Substituted-N-aminoalktlpiperazines may be prepared by reacting an N-substituted piperazine with a phthalimido alkyl halide followed by hydrolysis of the phthalimido alkyl piperazine so formed. Compounds of the formula H2N.A.B may be prepared by hydrolysing the corresponding phthalimidoalkylpiperazinium salts which may be prepared by the reaction of a phthalimidoalkyl halide with the corresponding piperazine or by reaction of the corresponding phthalimidoalkyl-piperazine with the appropriate quaternizing agent. 9 - (2 - Chloroethylamino) acridine may be prepared by treating the corresponding hydroxy compound with thionyl chloride. Therapeutic compositions with activity against trypanosomiasis, in the form of solutions, suspensions, tablets, granules or powders for parenteral or oral administration, comprises salts of cations of the Formula I and pharmaceutically acceptable acid addition salts thereof with a suitable pharmaceutical carrier.