Synthesis of 2-amino-3-cyano-4H-pyran derivatives using GO-Fc@Fe3O4 nanohybrid as a novel recyclable heterogeneous nanocatalyst and preparation of tacrine-naphthopyran hybrids as AChE inhibitors

GO-Fc@Fe 3 O 4 nanohybrid as a powerful and reusable nanocatalyst was synthesized. The graphene oxide (GO) sheets with meta-chloroperoxybenzoic acid (mCPBA) were treatment, afterward were chemically modified with 4-Fc derivative through the ring-opening reaction between GO nanosheets and 4-ferrocenylbutylamine. Then, the final nanocatalyst was obtained by synthesizing of Fe 3 O 4 nanoparticles onto the modified GO surface. The structure and morphology of GO-Fc@Fe 3 O 4 nanohybrid were characterized using different analysis, such as FT-IR, XRD, FE-SEM, EDX, and VSM techniques. Then, 2-amino-3-cyano-4 H -pyran derivatives ( 4a – l ) as a synthetic precursor were synthesized via multi-component reaction in the presence of GO-Fc@Fe 3 O 4 nanohybrid as a novel heterogeneous nanocatalyst. Finally, according to the importance of finding a solution to treat Alzheimer’s disease, 14-aryl-10,11,12,14-tetrahydro-9 H -benzo[5,6]chromeno[2,3-b]-quinolin-13-amines ( 5a – l ) as new tacrine-naphthopyran hybrid analogs were designed and prepared as acetylcholinesterase inhibitors. These compounds were synthesized via Friedländer reaction of 2-amino-3-cyano-4 H -pyran derivatives ( 4a – l ) with cyclohexanone. HAChE inhibition assay was carried out in vitro on the synthesized compounds 5a – l . Among them, compound 5f exhibited potent hAChE inhibitors with IC 50 values of 0.16 µM. Also, the molecular docking and kinetic studies performed for a better understanding of compound 5f as a representative compound. Graphic abstract