Abstract

Abstract In the current research work, we have prepared a series of pyrimidine moiety‐containing molecules due to their promising medicinal profile. First of all, we prepared two acetyl derivatives of pyrimidine ( 15 , 16 ), and then they reacted with different aryl aldehydes to form various chalcones in a 63–84% yield. The synthesized compounds were characterized by different analytical techniques and screened for their antidiabetic activity. Almost all synthesized compounds ( 17 – 43 ) showed good to excellent antidiabetic activity. Among all the synthesized compounds, 17 and 30 showed remarkable antidiabetic activity with IC 50 values of 5.118 µ m and 5.187 µ m respectively, as compared to the standard reference drug acrabose ( IC 50 = 37.38 µ m ). While compounds 18, 19, 21, 22, 23, 27, 31, 33, 38, 42, and 43 also showed excellent antidiabetic activity. Additionally, most biopotent drugs' molecular docking studies supported the distinct connections between substituent moieties and docking domains and agreed with the experimental findings. The molecular dynamics simulation study of the active compounds with the highest binding propensity to the enzyme revealed the robustness of the complexes from the docking study.