Design and Synthesis of 4,6-Dimethylpyrimidin-2-Amine Derivatives With Evaluation of Their Antifungal Activity

The development of novel antifungal agents has become increasingly important due to the emergence of fungal resistance and limitations associated with currently available therapies. In the present study, a novel pyrimidine Schiff base derivative, (E)-N-(4-chlorobenzylidene)-4,6-dimethylpyrimidin-2-amine (DP-1), was synthesized and evaluated for its antifungal potential. DP-1 was prepared through the condensation reaction of 4,6-dimethylpyrimidin-2-amine with 4-chlorobenzaldehyde under reflux conditions in ethanol. The synthesized compound was characterized by FTIR, ^1H NMR, ^13C NMR, mass spectrometry, and elemental analysis. Spectral studies confirmed the successful formation of the azomethine linkage and the proposed molecular structure. Molecular docking studies against fungal target protein (PDB ID: 2YZL) demonstrated favorable binding interactions with a docking score of −7.0 kcal/mol. DP-1 exhibited significant antifungal activity against selected fungal strains, indicating its potential as a lead compound for further optimization. The findings suggest that pyrimidine-based Schiff bases may serve as promising scaffolds for the development of new antifungal agents.