Synthesis of Novel Derivatives of 4,6-Diarylpyrimidines and Dihydro-Pyrimidin-4-one and In silico Screening of Their Anticancer Activity

: Derivatives of pyrimidinone, dihydropyrimidinone, and 2,4-diaryl-substituted pyrimidines were synthesized by cyclocondensation of α-aminoamidines with various sat-urated carbonyl derivatives and their analogs. The therapeutic potential of the newly syn-thesized derivatives for cancer treatment was evaluated using molecular docking calcula-tions. The molecular docking results indicate that some of the synthesized diaryl deriva-tives of pyrimidine exhibit high binding affinity towards PIK3γ. Aim and Objective: 4,6-Diaryl-substituted pyrimidines have shown high inhibitory poten-cy against phosphoinositide 3-kinases (PI3Ks), which are important targets in oncology. Inhibition of PI3Ks could potentially be a viable therapy for human cancers. Materials and Methods: The synthesis of pyrimidinone and dihydropyrimidinone deriva-tives as well as a series of 2,4-diaryl-substituted pyrimidines were described. These com-pounds were synthesized by cyclocondensation of α-aminoamidines with various saturated carbonyl derivatives and their analogs. Results: Derivatives of pyrimidinone, dihydropyrimidinone, and 2,4-diaryl-substituted py-rimidines were synthesized by combining α-aminoamidines with various saturated car-bonyl derivatives and their analogs. By adjusting the large substituents in the 2-position, we gained the ability to modify the therapeutic properties of the resulting compounds. The potential of the newly synthesized derivatives for cancer treatment was assessed using mo-lecular docking calculations. The results of the docking calculations suggest that some of the synthesized diaryl derivatives of pyrimidine have a strong binding affinity towards PIK3γ, making them promising candidates for the development of new anticancer medica-tions. Conclusion: We synthesized some pyrimidinones, dihydropyrimidinones, and 2,4-diaryl-substituted pyrimidines by combining α-aminoamidines with various saturated carbonyl derivatives and similar compounds. Molecular docking results suggest that certain diaryl derivatives of pyrimidine have a strong binding affinity for PIK3γ. Moreover, diphenyl de-rivatives of pyrimidine exhibited dual inhibitory activity against PI3K and tubulin, show-ing promise for the development of next-generation microtubule-targeting agents for use in combination therapies.