[Antimalarial active 10 H-indolo(3,2-b)quinolin-11-yl-amine. 2. Chloroquine analogs].
The quinolones 1b and 1c react with tosylisocyanate to yield the tosylamino quinolines 2b and 2c, while 1a under the same conditions gives the carbamate 5. Decarboxylation of 5 affords 2a. The mono and bis alkylated products 3 and 6 are received from 2b. The N-tosyl derivatives 2b and 3 rearrange to form the C-tosyl compounds 7 by heating with polyphosphoric acid (PPA) while 2c is hydrolized to 8c. 8 are isolated either from 2 using sulfuric acid 90% or from the 11-chloro-quinolines 9 melting in a mixture of ammonium chloride and acetate. The chloroquine analogues 4 are obtained from the 9-hydrochlorides with the dihydrochloride of the novaldiamine base. The quaternary salt 10 prepared by methylation of 9b reacts with the base in ethanol to yield 11. 4c inhibits the multi-resistant Plasmodium falciparum strain K-1 stronger than chloroquine.
Görlitzer
K
K
Institut für Pharmazeutische Chemie der Technischen Universität Braunschweig, Hamburg.
Stockmann
R
R
Walter
R D
RD
D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology; D002738:Chloroquine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D016778:Malaria, Falciparum / Q000097:blood / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects; D011804:Quinolines
C092774:10H-indolo(3,2-b)quinolin-11-ylamine; D000634:Aminoquinolines; D000962:Antimalarials; D007211:Indoles; D011804:Quinolines; D002738:Chloroquine