2-Acetylpyridine thiosemicarbazones. 12. Derivatives of 3-acetylisoquinoline as potential antimalarial agents.
A series of 3-acetylisoquinoline thiosemicarbazones and their related thiosemicarbazides was prepared for evaluation as potential antimalarial agents. The former were synthesized by the reaction of 3-acetylisoquinoline with methyl hydrazinecarbodithioate to give methyl 3-[1-(3-isoquinolinyl)ethylidene]hydrazinecarbodithioate, IV. Displacement of the S-methyl group of this intermediate by the requisite amines gave 3-acetylisoquinoline thiosemicarbazones, V. The corresponding thiosemicarbazides, in which the azomethine bond was reduced, were prepared by the reduction of IV with sodium borohydride to give methyl 3-[1-(3-isoquinolinyl)ethyl]hydrazinecarbodithioate, VI. Reaction of this dithioester with amines gave 1-[1-(3-isoquinolinyl)ethyl-3-thiosemicarbazides, VII. The antimalarial properties of series V and VII were evaluated in mice infected with Plasmodium berghei. Significant curative activity could be observed at doses as low as 40 mg/kg for 3 of 10 compounds in series V and at 160 mg/kg for 3 of 11 compounds in series VII.
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis*; D004353:Drug Evaluation, Preclinical; D007546:Isoquinolines / Q000138:chemical synthesis / Q000494:pharmacology; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D008813:Mice, Inbred ICR; D010962:Plasmodium berghei; D013882:Thiosemicarbazones / Q000138:chemical synthesis* / Q000494:pharmacology
D000962:Antimalarials; D007546:Isoquinolines; D013882:Thiosemicarbazones; C048160:3-acetylisoquinoline