Synthesis of Imidazo[1,2‐b]pyridazine Scaffold Based Amide Derivatives as Potential Inhibitors for Bacterial Activity

A series of fifteen novel amide derivatives based on imidazo[1,2‐b]pyridazine scaffold were synthesized by taking imidazo[1,2‐b]pyridazine‐3‐carboxylic acid intermediates with respective substituted amines to yield good to excellent. The molecular structures of the newly synthesized compounds were elucidated using spectroscopic techniques ( 1 H NMR, 13 C NMR, and LCMS) and supported by single‐crystal X‐ray diffraction (SXRD) for the two compounds, 9 and 18 . These compounds were evaluated in vitro for antimicrobial activity against two Gram‐positive bacteria ( S. aureus and B. subtilis ) and two Gram‐negative bacteria ( E. coli and P. aeruginosa ). Interestingly, compounds 10 and 16 , displayed comparable antibacterial activity to the positive control (Tetracycline: 6.25 μg/mL) against Gram‐negative bacteria, particularly Pseudomonas aeruginosa , with a minimum inhibitory concentration (MIC) of 6.25 μg/mL. Compound 17 exhibited moderate antibacterial activity with an MIC of 10 μg/mL against the Gram‐positive bacterium Bacillus subtilis, whereas the positive control demonstrated an MIC of 6.25 μg/mL. These antibacterial activities were found to have a good correlation with Insilco computational molecular docking experiments using the receptor UDP‐ N ‐acetylglucosamine‐enolpyruvate reductase, Mtb MurB .