Design, synthesis, bioactivity, DFT, and molecular docking of 4-aminoantipyrine analogs as potential analgesic and anti-inflammatory agents.

Our main interest lies in the synthesis, characterization, and evaluation of the pharmacological properties of bioactive compounds, with the aim of contributing to the development of alternatives to currently marketed drugs, whose effectiveness may be limited or decline over time. 4-Aminoantipyrine analogs represent a promising class of compounds of great biological interest, exhibiting a broad spectrum of pharmacological properties, particularly anti-inflammatory, antipyretic, and antimicrobial activities. In this study, we synthesized eight 4-aminoantipyrine derivatives, characterized by NMR (1H and 13C), IR, and HRMS. In vivo evaluation showed that compounds 3a, 3c, and 3d exhibited anti-inflammatory activity comparable to diclofenac, while analogs 3a-h displayed strong analgesic activity, surpassing that of aspirin, particularly for compounds 3b, 3c, 3d, 3e, 3f and 3g. The molecules 3a-h were compared using Gaussian software, calculating quantum chemical parameters. The activities of the high-activity molecules against various proteins COX-1 (PDB ID: 1EQG) and COX-2 (PDB ID: 3LN1, 4PH9) were then examined. Finally, ADME/T analysis was performed to examine their effects and reactions on human metabolism.