Studies on some 2-substituted-4-(furan-2-ylmethyl)-6-methylpyridazine-3(2h)-one derivatives

In this study, 16 new compounds, 2-[5-(furan-2-ylmethyl)-3-methyl-6-oxopyridazin-1(6H)-yl]-N-(aryl)acetamide (5a-j) and 4-(furan-2-ylmethyl)-6-methyl-2-[2-oxo-2-(4-arylpiperazin-1-yl)ethyl]pyridazin-3(2H)-one (6a-f), which are hybridization products of pyridazine-3(2H)-one and furan rings were synthesized and their antimycobacterial activities were investigated. 4-(2-Furylmethyl)-6-methylpyridazin-3(2H)-one (2) which was used as starting material in the synthesis of compounds was obtained by condensation of 6-methyl-4,5-dihydropyridazine-3(2H)-one (1) and furfural in the presence of potassium hydroxide. The reaction of compound 2 with 2-chloro-N-arylacetamides (3a-j) and 2-chloro-1-(4-arylpiperazin-1-yl)ethanones (4a-f) in the presence of potassium carbonate gave the target compounds (5a-j and 6a-f). The chemical structures of the synthesized compounds were elucidated by IR, 1H-NMR, 13C-NMR, mass spectroscopy and elemental analysis methods. In vitro activities of target compounds against M. tuberculosis H37Rv were investigated using the Microplate Alamar Blue Assay (MABA) method. Among the series, 5e, 5g, 5i and 6e were found to be the most active compounds with MIC of 50 µM against M. tuberculosis. The substitution of a chlorine (5e and 6e) at the phenyl ring increased antimycobacterial activity. On the other hand, the increased activity was observed by introducing larger groups such as biphenyl (5i, MIC = 50 µM) and naphthyl (5h, MIC= 100 µM) instead of smaller groups such as phenyl (5a, MIC= 200 µM) and pyridine (5j, MIC= 200 µM). These results showed that more studies are needed to gain pyridazin-3(2H)-ones with antitubercular activity.