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.

An efficient atom-economical synthetic protocol to access new imidazole-based
N-phenylbenzamide derivatives is described. A one-pot three-component reaction was
utilized to provide a series of N-phenylbenzamide derivatives in a short reaction time (2–4 h)
with an 80–85% yield. The cytotoxic evaluation revealed that derivatives 4e and 4f
exhibited good activity, with IC50 values between 7.5 and 11.1 μM against the tested
cancer cell lines. Computational studies revealed interesting insights: the docking of the
active derivatives (4e and 4f) showed a higher affinity toward the target receptor protein
than the control. Molecular dynamic simulations revealed that the active derivatives form
stable complexes with the ABL1 kinase protein. Moreover, the ADME and drug-likeness of
the derivatives reinforced the potential of the derivatives to be taken up for further
development as anticancer agents.

An efficient and catalyst-free multicomponent sequence for synthesizing fused new polyheterocyclic pyrene-grafted dispiro-pyrrolidine oxindolines through 1,3-dipolar cycloaddition reaction mediated by non-stabilized azomethine ylides is reported herein. The regio- and stereochemistry of the cycloadducts were determined on the basis of one-dimensional (1D) and two-dimensional (2D) homonuclear and het- eronuclear correlation NMR spectroscopy. The mechanism of the cycloaddition reaction, as well as regios- electivity were discussed by evaluating global and local electrophilicity and nucleophilicity descriptors at B3LYP/6-31G level of theory. The findings suggested that the polarity and charge transfer flow be- tween azomethine ylides (dipole) and 5-chloro-3-(2-oxo-2-(pyren-1-yl)ethylidene)indolin-2-ones (dipo- larophiles) was consistent with the global reactivity descriptors and substitutional pattern. These out- comes based on local descriptors Parr functions proposed by Domingo were found to be quite promising indices for the study of organic reactivity and to explain the regioselectivity of cycloaddition processes.