2-Acetylpyridine thiosemicarbazones. 8. Derivatives of 1-acetylisoquinoline as potential antimalarial agents.
A series of 1-acetylisoquinoline thiosemicarbazones was prepared in order to evaluate their antimalarial properties. This was achieved by the reaction of 1-acetylisoquinoline with methyl hydrazinecarbodithioate to give methyl 3-[1-(1-isoquinolinyl)ethylidene]hydrazinecarbodithioate (II). Displacement of the S-methyl group from this intermediate by various primary and secondary amines afforded the desired 1-acetylisoquinoline thiosemicarbazones (III). Thiosemicarbazides in which the azomethine moiety of the latter was reduced could be prepared by the reaction of II with NaBH4 to give methyl 3-[1-(1-isoquinolinyl)ethyl]hydrazinecarbodithioate (VIII). Reaction of VII with the appropriate amine gave 1-[1-(1-isoquinolinyl)ethyl]thiosemicarbazides (IX). Evaluation of the antimalarial activity of series III and IX in mice infected with Plasmodium berghei indicated that cures were attainable at dose levels of 40-160 mg/kg.
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000627:therapeutic use; D008288:Malaria / Q000188:drug therapy*; D051379:Mice; D010962:Plasmodium berghei / Q000187:drug effects; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000138:chemical synthesis* / Q000627:therapeutic use
D000962:Antimalarials; D007546:Isoquinolines; D013882:Thiosemicarbazones; C033836:2-acetylpyridine thiosemicarbazone