2-Acetylpyridine Thiosemicarbazones. 12. Derivatives of 3-Acetylisoquinoline as Potential Antimalarial Agents

摘要

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(-(3-iosquinoliny)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 of series VII.