GB878461A - Quinoline derivatives and the manufacture thereof - Google Patents

Abstract

The invention comprises 8-aminoquinoline derivatives of the formula <FORM:0878461/IV (b)/1> and acid addition salts thereof, wherein R1 and R2 are hydroxy or C1-C4 alkoxy groups or R2 may also be hydrogen, R3 is hydrogen or a C2-C4 alkyl group bearing a hydroxy substituent on at least one carbon atom other than that adjacent to the piperazine ring and X is a straight or branched aliphatic hydrocarbon chain of 3-7 carbon atoms, provided that, when R1 is a methoxy group X shall not be an unbranched hexamethylene group. The compounds are made by linking successive portions of the molecule by condensation reactions of compounds containing reactive substituents such as halogen atoms or alkyl or aryl sulphonyloxy groups, for example; (a) an 8-amino quinoline is treated with a reactive N1-R3-piperazinoalkyl compound; (b) N1-R3-piperazine is treated with an 8-quinolinylaminoalkyl reagent or (c) an 8-piperazinoalkylamino quinoline is treated with a hydroxyalkyl reagent, for example an alkylene oxide having 3 or 4 atoms in the ring. In processes (a) and (b) the N1-piperazinyl substituent may suitably be an alkoxycarbonyl group which is finally removed from the reaction product by hydrolysis. The compounds may also be prepared by reduction e.g. with lithium aluminium hydride, of a compound of the formula <FORM:0878461/IV (b)/2> wherein R4 has the same values as R3 and may also be an alkoxycarbonylalkyl group and Y is a radical -CO.Z-, -Z.CO- or -CO.W.CO-, wherein Z is an aliphatic hydrocarbon chain of 2 to 6 carbon atoms and W is an aliphatic hydrocarbon chain of 1 to 5 carbon atoms. Piperazino-quinoline compounds of the formula II used as intermediate compounds in the examples are prepared, when Y is a radical -CO.Z-, by treating an 8-amino quinoline with a haloacyl halide and condensing the resulting 8-haloalkanoyl-amino-quinoline e.g. 6-methoxy-8-chloropropionamidoquinoline, or, when Y is a radical -CO.W.CO-, by the reaction of the appropriate 8-aminoquinoline e.g. 6-methoxy-8-aminoquinoline, with a piperazine and succinic anhydride in the presence of N:N1-dicyclohexylcarbodiimide. Disubstituted piperazines used as starting materials, i.e. N-g -chloropropyl-N1-hydroxyethyl-, N-g -chlorobutyl-N1-carbethoxy- and N-b :g -dihydroxypropyl-N1-carbethoxy-piperazine are made by treating the appropriate monosubstituted piperazine with trimethylene chloro-bromide, 1-chlorobutan-3-ol and glycidol respectively. Bis[3 - (6 - methoxy-8-quinolylamino)-3-oxopropyl] piperazine is obtained by the action of 6-methoxy-8-(3-chloropropionamido) quinoline on piperazine. Specification 834,300 is referred to.