Potential antitumor agents. 14. 4 Substituted 2 formylpyridine thiosemicarbazones

Article abstract of DOI:10.1021/jm00232a008

A series of 4 substituted 2 formylpyridine thiosemicarbazones has been synthesized which contain a tertiary N at the 4 position. These materials were obtained by reacting 4 nitro 2 picoline N oxide, either directly or after conversion to the corresponding 4 chloro derivative, with a variety of secondary amines. Rearrangement of the 4 substituted 2 picoline N oxides with Ac₂O yielded respective methyl acetates, which upon acid hydrolysis, MnO₂ oxidation, and reaction with thiosemicarbazide resulted in the desired compounds. An alternate procedure which consisted of reacting 4 chloro 2 formylpyridine ethylene acetal with various amines, followed by hydrolysis and reaction with thiosemicarbazide, was also employed. Introduction of an alkyl group at the 3 position of the pyridine ring of 4 morpholino 2 formylpyridine thiosemicarbazone was achieved by utilizing 2,3 dimethyl 4 nitropyridine N oxide; this material was converted to the corresponding 4 chloro derivative which was then subjected to nucleophilic substitution. 4 Morpholino 2 formylpyridine thiosemicarbazone was the most active antineoplastic agent of this series in mice bearing Sarcoma 180 ascites cells and was significantly superior to 5 hydroxy 2 formylpyridine thiosemicarbazone in this test system.