Design, synthesis, and computational analysis of oxazine-based Schiff bases as prospective analgesic and anti-inflammatory agents

This work aimed to design and synthesize a series of Schiff base derivatives of 4-(3-methoxyphenyl)-6-(4-nitrophenyl)-6H-1,3-oxazin-2-amine with different aldehydes. The target compounds (G-1 to G-10) were synthesized using a three-step scheme; the characterization of synthesized compounds was carried out by FT-IR, ¹H NMR, and ¹³C NMR and evaluated for COX-1 and COX-2 inhibitory potential. Among the synthesized compounds, one benzylidene-[4-(3-methoxy-phenyl)-6-(4-nitro-phenyl)-6H-[1,3]oxazin-2-yl] -amine (G-1) had the most pronounced analgesic and anti-inflammatory effects, better than diclofenac sodium and indomethacin. Molecular docking and in silico prediction of ADMET properties of drugs were performed, respectively, considering the in vitro and in vivo results.