Synthesis of Phenoxy Substituted Imidazo[1,2‐b]Pyridazine‐Based Amide Derivatives for Antibacterial and Anti‐Tubercular Activities

ABSTRACT

A series of 10 phenoxy‐substituted imidazo[1,2‐b]pyridazine amide derivatives were synthesized from 6‐chloro‐2‐methyl‐8‐phenoxyimidazo[1,2‐b]pyridazine‐3‐carboxylic acid and respective amines. All these 10 compounds were characterized using spectroscopic analysis (¹H, ¹³C, HPLC, and ESI). Furthermore, the molecular structure obtained with spectroscopic analysis was confirmed by single‐crystal x‐ray diffraction (SXRD) analysis with a compound 12. All the 10 newly synthesized compounds were screened for in vitro antibacterial activities with the agar dilution method against two Gram‐positive bacteria (Staphylococcus aureus and Bacillus subtilis) and two Gram‐negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Compounds 11 and 13 both showed MIC values, 6.25 µg/mL, and comparable antibacterial activity to the positive control with the reference drug. Similarly, Mycobacterium tuberculosis H37Rv using the Microplate Alamar Blue Assay (MABA) and compounds 9 and 12 displayed moderate tubercular activities at a concentration of 25 µg/mL. The molecular docking studies correlated with biological activity against the active sites of PDB ID: 5JZX.