Aim: There has been an enormous commercial development following the introduction of selective COX-2 inhibitors. Efforts are continuously done to discover efficient and safe COX-2 inhibitors.
Results: A series of 4-methylsulfonylphenyl derivatives was designed, synthesized and screened for preferential inhibition of COX-2 over COX-1 isoforms and in vivo anti-inflammatory activity using the rat paw edema method. The most active ones were investigated via ulcerogenic liability and molecular docking. Physicochemical parameters were calculated for all the newly synthesized compounds.
Conclusion: The new compounds showed clear preferential COX-2 over COX-1 inhibition. Selective indices for compounds 4, 6b and 6e were 124, 131 and 119, respectively. Compound 4 reached 71% in vivo anti-inflammatory inhibition. The compounds obeyed 'Lipinski's rule of five'.
Keywords: anti-inflammatory; cyclooxygenase; methylsulfonylphenyl.