Patent GB-986350-A (GB)
Title: Aminoquinoline derivatives
IPC: C07J17/00
Filed: 1962-12-21
Abstract: The invention comprises compounds of general formula <FORM:0986350/C2/1> wherein the symbols A represent the same or different divalent straight or branched chain alkylene groups containing 2 to 6 carbon atoms, the symbols R1 have the same or different means and each represents hydrogen, halogen, alkyl, alkoxy, dialkylsulphamoyl, amino, alkanoylamino or trifluoromethyl in the 5, 6, 7 or 8-position, the symbols R2 in the 2- or 3-position have the same or different means and each represents hydrogen, halogen, alkyl; phenyl or phenyl substituted by a halogen atom or an alkyl group, the said alkyl and alkoxy groups and the alkyl and alkanoyl portions of said groups containing at most 3 carbon atoms, n is 2 or 3, and the diazacycloalkane ring may carry one or more substituent alkyl groups containing up to 4 carbon atoms; and their steroisomers; and their acid addition salts; except certain optically inactive 1,4-di-(7-chloro-4-quinolylaminoalkyl) piperazines and their acid addition salts according to Specification 973,903; and the preparation of the compounds claimed by (I) reacting a compound of formula <FORM:0986350/C2/2> with 2 moles of a 4-Y-R1, R2, quinoline where Y is a chlorine atom or a phenoxy group, (2) reacting a diazacycloalkane with 2 moles of a compound of formula <FORM:0986350/C2/3> where X represents the acid residue of a reactive ester and R represents hydrogen or a protecting group which is subsequently removed in known manner, (3) reacting a compound of formula <FORM:0986350/C2/4> with a compound of formula III, or (4) deacylating in known manner a compound wherein R1 is alkanoylamino. Substituted aminoquinolines IV may be prepared by reacting a 4-Y-R1, R2, quinoline with a compound <FORM:0986350/C2/5> where R1 is a subsequently removable protecting group or analogously to process (2) using excess of diazacycloalkane.  Diazacycloalkanes II and substituted aminoquinolines III may be prepared by methods known or analogous to those of Specification 973,903.  3 - Carbethoxy - 7 - dimethylsulphamoyl - 4 - hydroxyquinoline is prepared from 3-dimethylsulphamoylaniline and ethyl ethoxymethylene-malonate, and on saponification yields the 3-carboxy-compound which is decarboxylated to 7 - dimethylsulphamoyl - 4 - hydroxy - quinoline from which the 4-chloro-compound is obtained with phosphorus oxychloride.  1,4 - bis - [4 - (4 - quinolyl) (acetyl) - aminopentyl] - piperazine and its dimaleate is obtained from 4 - [(5 - 11 - piperazinyl - 2 - pentyl) (acetyl)] - amino - quinoline and 4 - [(5 - methanesulphonyloxy - 2 - pentyl) (acetyl)] - aminoquinoline. The 6-methoxy-quinoline is similarly obtained.  4 - (5 - Hydroxy - 2 - pentyl) - aminoquinoline is obtained from 4-chloroquinoline and 2-amino-pentam-5-ol and with acetic anhydride yields the di-O,N-acetyl derivative which is hydrolysed to the N-acetyl compound; methanesulphonylchloride yields 4 - [(5 - metahnesulphonyloxy-2 - pentyl)(acetyl)]aminoquinoline which on reaction with piperazine gives 4[(5-11-piperazinyl-2 - pentyl)(acetyl)]aminoquinoline.  The corresponding 6-methoxyquinolines are similarly obtained.  1,4 - bis - (2 - oximino - propyl) - hexahydro-1,4-diazepine is obtained from the ketone and hydroxylamine and is hydrogenated to the bis-(2-amino-propyl) -compound.  4 - (3 - Hydroxy - 2 - propyl)aminoquinolines having 6-chloro, 7-chloro, or 7-methoxy substituents are obtained from 2-aminopropanol and 4-chloroquinolines and with thionyl chloride yields the 3-chloro-2-propyl-compounds.  1,4 - bis - (2 - cyanoethyl) - hexahydro - 1,4-diazepine is prepared from hexahydro-1,4-diazepine with acrylonitrile and is hydrogenated to the 1,4-bis-(3-aminopropyl)-compound.  D- and L - 4 - (3 - hydroxy - 2 - propyl)amino-7-chloroquinolines are obtained from 4,7-dichloroquinoline and alaninols, and with thionyl chloride yield the (3-chloro-2-propyl)-compounds; reaction with piperazine produces D- and L-4-(3 - 11 - piperazinyl - 2 - propyl) amino - 7 - chloroquinolines.  Pharmaceutical compositions comprise compounds and non-toxic acid addition salts of the invention with pharmaceutical carriers or coatings.  Compositions (tablets, pills, powders, granules, capsules, syrups, elixirs, solutions, suspensions, emulsions, suppositories) are mentioned for oral, parenteral and rectal administration. The compounds have antimalarial, anthelmintic, amoebicidal, antiinflammatory and antirheumatic activities.