Synthesis and in Silico Study of Novel Benzisoxazole‐Chromene Derivatives as Potent Inhibitors of Acetylcholinesterase: Metal‐Free Site‐Selective C−N Bond Formation via Aza‐Michael Reaction

Abstract

AbstractAn efficient metal‐free approach for site selective C−N coupling reaction of benzo[d]isoxazole and 2H‐chromene derivatives has been designed and developed against AchE. This nitrogen containing organo‐base promoted methodology, which is both practical and environmentally friendly, provides an easy and suitable pathway for synthesizing Benzisoxazole‐Chromene (BC) possessing poly heteroaryl moieties. The synthesized BC derivatives 4 a–n was docked into the active sites of AChE to obtain more perception into the binding modes of the compounds. Out of them, compound 4 a and 4 l displayed potent activity and high selectivity against the AChE inhibition. Final docking results indicates that compound 4 l showed the lowest binding energy of −11.2260 kcal/mol with AChE. The synthesized BC analogs would be potential candidates for promoting suitable studies in medicinal chemistry research.