ANTI-MALARIA ACTIVE 10H-INDOLO[3,2-B]QUINOLINE-11-YL-AMINES .2. CHLOROQUINE ANALOGS

The quinolones Ib and Ic react with tosylisocyanate to yield the tosyl amino quinolines 2b and 2c, while la under the same conditions gives t he carbamate 5. Decarboxylation of 5 affords 2a. The mono and bis alky lated products 3 and 6 are received from 2b. The N-tosyl derivatives 2 b and 3 rearrange to form the C-tosyl compounds 7 by heating with poly phosphoric acid (PPA) while 2c is hydrolized to 8c. 8 are isolated eit her 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 dihydroch loride of the novaldiamine base. The quaternary salt 10 prepared by me thylation of 9b reacts with the base in ethanol to yield 11. 4c inhibi ts the multiresistant Plasmodium falciparum strain K-1 stronger than c hloroquine.