Synthesis and anti-proliferative activity studies of 2-(2-(trifluoromethyl)-6-(substituted)imidazo[1,2-b]pyridazin-3-yl)-N-(substituted)acetamide derivatives

A series of novel imidazo[1,2-b]pyridazin-3-yl acetamide derivatives (9a-9j) were synthesized from a 3,6-dichloropyridazine. We have developed a simple strategy for the synthesis of functionally diverse imidazole, and pyridiazine derivatives were reported via a series of steps. The work involves bicyclic imidazo-pyridazine ring formation, halogenation, cynation, hydrolysis, peptide coupling, and Buchwald reaction. The structure of the synthesized compounds was confirmed by IR, H-1 NMR, C-13 NMR,F-19 NMR, mass spectra, and elemental analysis, and purity is checked by HPLC. All synthesized compounds were screened for anticancer activity against A-549 and Du-145 cancer cell lines by MTT assay. The preliminary bioassay suggests that most of the compounds show anti-proliferation with different degrees; doxorubicin was used as positive control. The synthesized compound shows IC50 values in the range of 1.74 mu M to 16.17 mu M in both cell lines. The compounds 9e, 9g, and 9h were active compared with doxorubicin in both the cell lines. The compounds having cyclopentyl ring are active compared with higher and lower carbon analogues.