Access to new phosphonate- and imidazolidine-benzopyrimidinone derivatives as antityrosinase and anti-acetylcholinesterase agents: Design, synthesis and molecular docking

•A series of new benzopyrimidinone derivatives was designed, synthesized and characterized.•All compounds were tested in vitro for their antityrosinase and anti-acetylcholinesterase activities.•Compounds 3g, 4b and 5f exhibited the highest tyrosinase inhibition.•Compounds 3g, 3d, and 5f displayed interesting anti-acetylcholinesterase activity amongst all compounds synthesized and tested.•Molecular docking studies confirmed the activity of some derivatives. To discover new acetylcholinesterase and tyrosinase inhibitors, a series of dialkyl phosphonate-benzopyrimidinones 4a-b was prepared via Michaelis-Arbuzov rearrangement (Arbusov reaction) of benzopyrimidinone chloride 2 with trialkyl phosphate, as well as a series of imidazolidine-benzopyrimidinone derivatives 5a-g synthesized by Mannich reaction of 2-((arylamino)methyl) benzopyrimidin-4(3H)-one 3 with formaldehyde. The structures of the new target compounds were investigated by 1H NMR, 13C NMR and ESI-HRMS. All synthesized compounds were evaluated for their anti-acetylcholinesterase and antityrosinase activities. Compounds 5f, 3g and 4b showed the highest tyrosinase inhibition and compounds 3g, 3d and 5g were found to be the most anti-acetylcholinesterase agents. Moreover, structure activity relationship (SAR) was discussed for all synthesized compounds and the interaction modes of the most potent inhibitors were confirmed through molecular docking studies. [Display omitted]