Access to Imidazopyrazine Conjugated Benzamides as Potential Anticancer Agents

A series of 2-(5,6-dicyano-1 H -imidazo[4,5- b ]pyrazin-2-yl)- N -phenylbenzamides was prepared in 80–85% yield by one-pot three-component reaction of isobenzofuran-1,3-dione with anilines and 5,6-diaminopyrazine-2,3-dicarbonitrile in the presence of phosphoric acid as a catalyst and glycerol as a solvent at 80–90°C. The developed protocol has the advantages of short reaction times, high yields, mild reaction conditions and environmental friendliness. The synthesized compounds were assessed for their ability to impede cancer growth in DU145 and MCF7 cells. Among the compounds tested, N -(4-chlorophenyl)benzamide derivative demonstrated significant cytotoxicity, with IC50 values of 8.9 and 9.7 µM against DU145 and MCF7, respectively. Furthermore, computational studies indicated that this compound exhibited a favorable binding energy of –10.3 kcal/mol when compared to the co-crystal ligand (NRM) in inhibiting the human aurora kinase protein.