The most effective antimalarial agents among the N4-monosubstituted 2-acetylpyridine thiosemicarbazones recently described by us have a cyclohexyl or a phenyl substituent and produce cures in Plasmodium berghei infected mice at a dose of 160 and 320 mg/kg, respectively. We report here on a related series of N4,N4-disubstituted 2-acetylpyridine thiosemicarbazones. Several members of this group bearing alkyl or cycloalkyl substituents at N4 show activity superior to the most active monosubstituted 2-acetylpyridine thiosemicarbazones. However, the greatest improvement in potency was seen when the N4-nitrogen atom was incorporated into a six- or seven-membered ring, such as the piperidine, piperazine, or azabicyclo[3.2.2]nonane systems, to give compounds with curative properties at a dose level as low as 20 mg/kg.

No abstract

Aus den Acylpyridinen (I) erhält man mit dem Dithiokohlensäurehydrazid (ll).die Hydrazone (III), die mit Aminen (IV) zu den Thiosemicarbazonen (V) umgesetzt werden.

Das 3‐Acetylisochinolin (I) kondensiert mit dem Dithiocarbazidsäuremethylester (II) zum Hydrazon (III), das sich mit NaBH4 zum Hydrazinodithiocarbonsäureester (IV) hydrieren läßt. Die sekundären Amine (VI) liefern mit (III) die Thiosemicarbazone (V); mit (IV) entstehen die Thiosemicarbazide (VII).