Novel Pyrimidine Derivatives Incorporating a Semicarbazide Moiety as Potential Antioxidant Inhibitors: Synthesis, Antioxidant Activity, Molecular Docking, ADMET, and Drug-likeness Studies

In this study, a series of novel pyrimidine derivatives incorporating a semicarbazide moiety were synthesized, and their structures were comprehensively characterized by means of 1H, 13C NMR, and HRMS. Biological evaluation revealed that compound N-benzyl-2-(4,6-dimethylpyrimidin-2-yl)hydrazine-1-carboxamide exhibited significant in vitro DPPH and ABTS radical scavenging activities, with IC50 values of 4.9 and 3.8 μg/mL, respectively, lower than those of the reference antioxidants vitamin C (6.4 μg/mL) and Trolox (8.4 μg/mL). Meanwhile, molecular docking analysis further demonstrated that compound N-benzyl-2-(4,6-dimethylpyrimidin-2-yl)hydrazine-1-carboxamide engages in multiple intermolecular interactions within the active site of NADPH oxidase (PDB ID: 2CDU), including van der Waals forces, conventional hydrogen bonds, π-sulfur, alkyl, and π-alkyl interactions. Furthermore, ADMET profiling and drug-likeness assessments indicated that N-benzyl-2-(4,6-dimethylpyrimidin-2-yl)hydrazine-1-carboxamide possesses favorable physicochemical properties and an acceptable safety profile, consistent with the characteristics of promising drug candidates. To the best of our knowledge, this work constitutes the first systematic investigation of pyrimidine derivatives bearing a semicarbazide scaffold.