Arzneimittel Forsch
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Arzneimittel Forsch · Jan 1984
A quantitative analysis of steric and hydrophobic effects in ribonucleoside diphosphate reductase inhibition by thiosemicarbazones.
Ribonucleoside diphosphate reductase (RDR) inhibitory activity of 2-formylpyridine and 1-formylisoquinoline thiosemicarbazones is quantitatively analysed in relation to a steric parameter (van der Waals volume, VW) and the hydrophobic parameter logP. The activity is found to be significantly correlated with VW and very poorly with logP. On the basis of this, it is inferred that RDR inhibition by thiosemicarbazones is very sensitive to steric effects and is little influenced by the hydrophobic character of the molecules.
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Arzneimittel Forsch · Jan 1984
2-Acetylpyridine thiosemicarbazones. 10. 2-Propionyl-, 2-butyryl-, and 2-(2-methylpropionyl)pyridine thiosemicarbazones as potential antimalarial agents.
In view of the antimalarial properties observed for many 2-acetylpyridine thiosemicarbazones, a series of N4,N4-disubstituted 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. ⋯ The three thiosemicarbazones derived from 3-azabicyclo[3.2.2]nonane were most 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 contrast to the related thiosemicarbazones derived from 2-acetylpyridine, virtually no toxic effects were observed in the series described here.