Expanding the Horizon of Pteridine Chemistry: Optimized Synthesis by the Isay Reaction, and Molecular-Docking Studies

Abstract The Isay reaction was used to synthesize novel disubstituted pteridine derivatives. The pteridine scaffold was synthesized by reacting a mercaptopyrimidine derivative with a substituted diketone, followed by a reaction with a substituted phenylurea derivative. Standard physicochemical and spectroscopic techniques, such as FTIR, mass spectrometry, 1H NMR, D2O exchange, and HPLC confirmed the structures and purities of the synthesized compounds. Various key substituents on the phenylurea and on the pteridine scaffold were incorporated to explore their effects on the chemical and biological properties of the products. Molecular-docking studies against proteins PI3K (PDB ID: 4L23) and mTOR (PDB ID: 4JT6), showed promising interactions that supported the potential biological activity of the pteridine derivatives. These findings provide a strong basis for further optimization and biological evaluation, particularly in the development of novel anticancer agents.