Synthesis and Biological Activity of Functionally Substituted Pyrimidine and Pyran Derivatives on the Basis of Isatylidene Malononitriles

Abstract

AbstractIn this study, it was shown that pyrimidine and imidazopyridine derivatives were obtained from the multicomponent reaction of isatylidene malononitriles with malononitrile and diamines at room temperature. Also, the interaction of 2‐(5‐bromo‐2‐oxoindoline‐3‐ylidene)with malononitrile and benzoyl acetone (or ethyl‐4‐chlorine‐acetoacetate) was carried out and the formation of the corresponding pyran derivatives was observed.The structure of the synthesized compounds was confirmed by 1H, 13CNMR spectroscopy and X‐ray analysis. The acetylcholinesterase (AChE) inhibitor compounds recorded as important therapeutic drugs for the therapy of Alzheimer's disease. Also, novel complexes effectively inhibited AChE enzyme, with Ki values in the range of 4.56 to 8.21 μM. For this enzyme, it was obtained with IC50 values in the range of 4.04 to 9.85 μM. For α‐glycosidase enzyme the most effective Ki values were for 4 a and 10 compounds with Ki values of 31.48 and 32.63 μM, respectively. The molecular docking study was employedto investigate of chemical activities and interaction of synthesized compounds with low Ki in the presence of AChE, butyrylcholinesterase, and α‐Glycosidase. The results revealed that some of the compounds, like compound 9 have a good binding affinity to AChE with a docking score of −6.243 (kcal/mol). This compound can affect the enzyme activity by attachment to essential residues of the catalytic domain of the enzyme. The ADME/T analysis was also performed and revealed that compounds have the potential to be utilized as medicine.