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

GO-Fc@Fe3O4 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 Fe3O4 nanoparticles onto the modified GO surface. The structure and morphology of GO-Fc@Fe3O4 nanohybrid were characterized using different analysis, such as FT-IR, XRD, FE-SEM, EDX, and VSM techniques. Then, 2-amino-3-cyano-4H-pyran derivatives (4a–l) as a synthetic precursor were synthesized via multi-component reaction in the presence of GO-Fc@Fe3O4 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-9H-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 Friedlander reaction of 2-amino-3-cyano-4H-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 IC50 values of 0.16 µM. Also, the molecular docking and kinetic studies performed for a better understanding of compound 5f as a representative compound.