GB1445595A - 4-aminoquinoline derivatives and intermediates for their pre paration - Google Patents

Abstract

1445595 4-Aminoquinoline derivatives, their preparation and pharmaceutical compositions JOHN WYETH & BRO Ltd 4 Sept 1974 [6 Sept 1973] 41902/73 Heading C2C The invention comprises compounds of general Formula I or an acid addition salt thereof wherein X is a halogen atom or a CF 3 group; Z is a hydrogen or halogen atom, a CF 3 group or a C 1-6 alkyl, C 1-6 alkoxy, OH, NO 2 , NH 2 or mono or dialkylamino group and R represents (i) a group of Formula II in which A represents a C 1-5 polymethylene chain optionally substituted by one or more alkyl groups; R 1 is a hydrogen atom or an alkyl, aralkyl, acyl or aryl group; R 2 is a hydrogen atom or an alkyl, aralkyl or acyl group or R 1 and R 2 may form together the diacyl residue of a dicarbonylic acid or a divalent radical such that R 1 R 2 NH is a secondary cyclic amine with 5 to 7 ring atoms; (ii) a group of Formula IIIa in which the ring is a piperidine or pyrrolidine ring optionally substituted by one or more alkyl groups or by a divalent aliphatic chain substituting two different ring members of said ring; R 1 is as defined above and R 3 is a hydrogen atom, a C 5-7 cycloalkyl group, an alkyl or aralkyl group, an alkyl group substituted by a heterocyclic group, or an aliphatic chain joining the nitrogen atom to another member of the same ring or (iii) a group of Formula IIIb in which the ring, R 1 and R 2 are as defined above. The compounds of Formula I may be prepared by (a) reacting a compound of formula where R is as defined above, or if desired a corresponding compound having a reactive functional group therein protected with a sulphonylation agent, e.g. a sulphonyl chloride to introduce the group of Formula XIV wherein X is as defined above and Z is as defined above or is a protected amino or OH group; (b) reacting a compound of Formula XVI wherein R is as defined above and Z is as defined for Formula XIV with a compound of Formula XVII wherein X is as defined above and Q is a leaving group, e.g. I, Br, Cl or an organic sulphonate; (c) reacting a compound of Formula XXV where X and Z are as defined for Formula XIV is alkylated to introduce the group -ANR 1 R 2 or the group of Formula IIIc (d) subjecting a compound of Formula XXV (above) to two successive alkylations, one to introduce the group -ANR 1 R 2 and the other to introduce an alkyl group R 3 or (e) subjecting a compound of Formula XXV (above) to two successive alkylations, one to introduce the group of Formula IIIa (above) the other to introduce an alkyl or aralkyl group as R 1 ; and if necessary a protecting group is removed and if desired a free base form of the compound of Formula I is converted into an acid addition salt or an acid addition salt of such a compound is converted into the free base form. 4 . (7 - Chloroquinolylamino) - benzene sulphonic acid is prepared by reacting 4,7-dichloroquinoline with p-aminobenzene sulphonic acid in phenol and is then reacted with thionyl chloride to obtain 4-(7-chloroquinolylamino)- benzenesulphonylchloride. 4 - Acetamido N- (1 - n - butyl - 4 - piperidyl) - benzenesulphonamide is prepared by reacting N-acetylsulphanilylchloride with 4-amino-1-n-butylpiperidine and is refluxed with aqueous NaOH to obtain 4 - amino N - (1 - n - butyl - 4 - piperdyl)- benzenesulphonamide. 3-(4-Acetamidobenzenesulphonamido) - 1 - ethylpiperidine is prepared by reacting 3-amino-1-ethylpiperidine with 4 - acetamidobenzenesulphonyl chloride and is hydrolysed by refluxing with aqueous NaOH to obtain 3 - (4 - amonibenzenesulphonylamido)- 1- ethylpiperidine. Pharmaceutical compositions having antihypertensive activity and also antimalarial, anti-inflammatory and anti-trichmonal activity and also inhibition of blood platelet aggregation comprise a compound of Formula I or pharmaceutically acceptable salt thereof together with a non-toxic carrier.