Synthesis and biological evaluation of 3-O-substituted 1-benzyl-6-oxo-1,6-dihydropyridazine derivatives

On the basis of 2-benzyl-6-hydroxypyridazin-3(2H)-one, a series of its novel O-substituted (including 6-(1,3,5-triazin-2-yl)oxy) derivatives is prepared. It is proven that the substitution reactions in the initial compound occur mainly at the oxygen atom of the hydroxy group. On the basis of the obtained oxy-aceto(propane)hydrazides, the corresponding azides and anilides are synthesized. A series of 2-[(1-benzyl-6-oxo-1,6-dihydropyridazin-3-yl)oxy]-N′-(substituted benzylidene)aceto(propane)hydrazides is obtained via the reaction of various aromatic aldehydes with the same hydrazides. Heterocyclization of the latter affords compounds with a combination of pyridazine and 1,3,4-oxadiazole rings in the molecule. The reaction of oxy-acetohydrazide with potassium thiocyanate and a mixture of CS2/KOH leads to potassium salts of 2-{[(1-benzyl-6-oxo-1,6-dihydropyridazin-3-yl)oxy]methyl}hydrazine-1-carbothioamide and 2-{2-[(1-benzyl-6-oxo-1,6-dihydropyridazin-3-yl)oxy]acetyl}hydrazine-1-carbodithioic acid, respectively. Acid hydrolysis of the latter affords 2-benzyl-6-[(5-thioxo-4,5-dihydro-1,3,4-thiadiazol-2-yl)methoxy]pyridazin-3(2H)-one.