Arzneimittel Forsch
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Arzneimittel Forsch · Jan 1986
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. ⋯ 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.