Synthesis and Anti‐inflammatory Effect of Simple 2,3‐Diarylindoles. On Route to New NSAID Scaffolds

Abstract Nitrogen‐containing drugs represent one of the worldwide most extensive sources of treatments for different diseases. Indomethacin as example, is one of the most important non‐steroidal anti‐inflammatories (NSAID) indol‐containing drug. Its relevance has been demonstrated the last 50 years with excellent pharmacological results. Its efficacy as an anti‐inflammatory treatment, inspired us the exploration of indol‐containing structurally less elaborated compounds which kept and/or improve the anti‐inflammatory activity compared with indomethacin. Herein is summarized and discussed our initial findings on the synthesis and anti‐inflammatory effect of different 2,3‐diarylindoles, designed for strategically favoring the plausible and selective interactions with COX‐2, on route to new simple NSAID scaffolds. The TPA model and formalin test were used in this study to generate inflammation in mice for conducting the assays with the synthesized 2,3‐diarylindoles. Docking analysis revealed stronger N−H indolic interactions with COX‐2 for 6‐methoxy‐2‐phenyl‐3‐(4‐chlorophenyl)‐1 H ‐indole, one of the most active of the synthesized compounds when compared with indomethacin. This, experimentally match with the anti‐inflammatory observed effect and putatively indicates the biochemical action mechanism.