Synthesis of pyrimido[5,4-c]quinolines and related quinolines as potential antimalarials.
3-Ethylaminomethyl-2-methyl-4(1H)-quinolone (1a) and its 6-CH3, 6-OCH3, and 7-Cl derivatives were prepared by means of the Mannich reaction. Conversion to the 4-chloro derivatives and condensation with 3-chloroaniline gave the corresponding 4-(3-chloroanilino) derivatives. Cyclization of 4-(3-chloroanilino)-2,6-dimethyl-3-ethyl-aminomethylquinoline (3a) and its 6-OCH3 derivative with paraformaldehyde gave 1-(3-chlorophenyl)-3,9-dimethyl-3-ethyltetrahydropyrimido[5,4-c]quinoline (4a) and the 9-OCH3 derivative 4b. Treatment of 4b with benzaldehyde gave 1-(3-chlorophenyl)-3-ethyl-9-methoxy-5-styryltetrahydropyrimido[5,4-c]quinoline (5). 3-Benzylaminomethyl-6-methoxy-2-methyl-4(1H)-quinolone (1e) and 3,3'-(1,3-benzyliminodimethylene)di[2-methyl-4(1H)-quinolone] (6b) were also synthesized. The compounds were inactive as antimalarials.
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis; D002645:Chickens; D004353:Drug Evaluation, Preclinical; D008288:Malaria / Q000188:drug therapy*; D051379:Mice; D010962:Plasmodium berghei; D011743:Pyrimidines / Q000138:chemical synthesis / Q000627:therapeutic use; D011804:Quinolines / Q000138:chemical synthesis / Q000627:therapeutic use*
D000962:Antimalarials; D011743:Pyrimidines; D011804:Quinolines