Multicomponent synthesis, cytotoxicity, and computational studies of novel imidazopyridazine-based N-phenylbenzamides

Abstract

A one-pot multicomponent synthesis and application of new imidazopyridazine based N-phenylbenzamides is described. An atom-economical method involving dimethyl phthalate, substituted anilines, and pyridazine-4,5-diamine provided the desired compounds in 120–150 min with 80–85% yield. The reaction was catalyzed with phosphoric acid, and glycerol was used as a safer, greener solvent. Anticancer evaluation against selected cancer cell lines revealed that compound 4e was the most active from the series and exhibited IC50 values below 9.1 µM. Compounds 4h and 4d also displayed good and comparable IC50 values (10.2–12.1 µM). Molecular docking and molecular dynamic studies showed that compound 4e exhibit good binding affinity and stable complex formation with ABL1-kinase protein, respectively. Additional computational predictions such as ADME and drug-likeness demonstrated the potential of the new benzamides as leads for further development.

Keywords

• Imidazopyridazine
• N-Phenylbenzamide
• Multicomponent reaction
• Cytotoxicity
• Computational studies