Design, Synthesis, and Characterization of Novel 3-(2-Amino-6-arylpyrimidin-4-yl)-1-methylquinolin-2(1H)-one Derivatives and Screening for Their Antioxidant and Acetylcholinesterase Inhibitory Potency

The cholinergic hypothesis is a fundamental approach employed in the research and discovery of new anti-Alzheimer therapeutics. In this context, a series of 3-[2-amino-6-(substituted phenyl)pyrimidin-4-yl]-1-methylquinolin-2(1H)-one derivatives 4a–4j were synthesized by condensing guanidine with 1-methyl-3-[(E)-3-oxo-3-(substituted phenyl)prop-1-en-1-yl)quinolin-2(1H)-ones 3a–3j which were prepared by condens­ing 1-methyl-2-oxo-1,2-dihydroquinoline-3-carbaldehyde (1) with various substituted acetophenones 2a–2j. The structures of the synthesized compounds were confirmed by elemental analysis, 1H and 13C NMR, IR, and mass spectrometry. Compounds 4a–4j were evaluated for their antioxidant activity using the DPPH method and for acetylcholinesterase inhibition by Ellman’s assay. Compounds 4c, 4e, 4g, and 4j exhibited excellent antioxidant activity compared to the standard (ascorbic acid). Most of the compounds showed moderate to good (4a, 4c, 4f, and 4g) AChE inhibitory activity. The results demonstrated that compound 4c with strong AChE inhibitory activity is promising for further investigation aimed at discovering novel AChE inhibitors that could be employed in the management of Alzheimer’s disease.