2-Acetylpyridine Thiosemicarbazones. 10. 2-Propionyl-, 2-Butyryl-, and 2-(2-Methylpropionyl)Pyridine Thiosemicarbazones as Potential Antimalarial Agents

摘要

In view of the antimalarial properties observed for many 2-acetylpyridine thiosemicarbazones, a series of N4,N4-disubituted thiosemicarbazones derived from 2-propionyl-, 2-butyryl-, and 2-(2-methylpropionyl)pyridine was prepared for evaluation against the malaria parasite, Plasmodium berghei, in the mouse. The thiosemicarbazones were made by the reaction of methyl hydrazinecarbodithioate with a 2-acylpyridine to give the intermediate methyl 3-(1-(2-pyridinyl)alkylidene) hydrazinecarbodithioates. Reaction of the latter with 3-azabicyclo-(3.2.2)nonane, 1-(2-pyridinyl)piperazine, or 1H-hexhydroazepine gave the requisite thiosemicarbazones. The three thiosemicarbons derived from 3-azabicyclo(3.2.2)nonane were mose effective, the greatest potency being exhibited by 3-azabicyclo- (3.2.2)nonane-3-thiocarboxylic acid 2-(1-(2-pyridinyl)butylidene)hydrazide (4) which cured 4/5 mice at a dose of 160 mg/kg. In contract to the related thiosemicarbazones derived from 2-acetylpyridine, virtually no toxic effects were observed in the series described here.