The Synthesis and Anti-inflammatory Studies of New Pyrimidine Derivatives, Inhibitors of Cyclooxygenase Isoforms

— Using the molecular docking approach the simulation of the complex formation of 17 uracil derivatives containing cyclic and acyclic sulfur- and oxygen substituents in the pyrimidine cycle with active centers of cyclooxygenase isoforms (COX) was performed. Of the set tested, two leading compounds were identified, namely, conjugates of 5-hydroxy-1,3,6-trimethyluracil with N -phthalyl-L-amino acids, which can be effective inhibitors of COX isoforms induced during inflammatory processes in the organism with an increased selectivity towards COX-2. The synthesized compounds were evaluated in vivo on the models of inflammation caused by carrageenan, lidocaine, egg white, and formalin. The conjugates of 5-hydroxy-1,3,6-trimethyluracil with N -phthalyl alanine and N -phthalyl methionine displayed pronounced anti-inflammatory activities with the efficacy comparable to that of Ortofen. The isoenzyme-specific inhibition of COX isoforms was assessed and the pronounced anti-inflammatory activity of the synthesized compounds was found.