Design, synthesis and in silico evaluation of benzoxazepino(7,6-b)quinolines as potential antidiabetic agents

The second-generation XPhos palladium preformed catalyst-based C–N cross-coupling through Buchwald–Hartwig amination with primary and secondary amines towards functionalized benzoxazepino(7,6-b)quinolines is accounted for. The microwave irradiation in dioxane provided the desired highly functionalized oxazepino quinolines, 5, in high yield and purity from the corresponding 2-chloro-3-formyl quinolines, 1, via intermediate, 4, in a sequential cyclization/Buchwald amination strategy. Besides, functional group tolerance, low catalyst loading, microwave assistance, and a wide scope of reactions are the advantages. Compounds 5a, 5b, 5c, 5d, 5e, and 6j showed 50% inhibition in antioxidant potency, whereas compounds 5f, 5g, 5m, 6h, 6j, and 6k showed potent activity alongside 70% inhibition of alpha-amylase and 50% inhibition of alpha-glucosidase, respectively. The results were supported by molecular docking studies of the active compounds with acarvostatin as a standard drug for antidiabetic activity.