Celecoxib analogs bearing benzofuran moiety as cyclooxygenase-2 inhibitors: Design, synthesis and evaluation as potential anti-inflammatory agents

• Novel series of celecoxib analogs endowed with benzofuran moiety were synthesized.
• The synthesized compounds were evaluated for their COX-1/COX-2 inhibitory activity.
• The pyridin-3-yl derivatives 3c and 3e showed the highest anti-inflammatory activity.
• The tested compounds had better gastric safety profile compared to celecoxib.
• Docking simulation of the new compounds in COX-2 active site was performed.

Novel series of celecoxib analogs endowed with benzofuran moiety 3a–e and 9a–d were synthesized and evaluated for COX-1/COX-2 inhibitory activity in vitro. The most potent and selective COX-2 inhibitors – compounds 3c, 3d, 3e, 9c and 9d – were assessed for their anti-inflammatory activity and ulcerogenic liability in vivo. The 3-(pyridin-3-yl)pyrazole derivatives 3c and 3e exhibited the highest anti-inflammatory activity, that is equipotent to celecoxib. Furthermore, the tested compounds proved to have better gastric safety profile compared to celecoxib. In particular, compound 3e demonstrated about 40% reduction in ulcerogenic potential relative to the reference drug. Finally, molecular docking simulation of the new compounds in COX-2 active site and drug likeness studies showed good agreement with the obtained pharmaco-biological results.

The present work reports the synthesis of novel celecoxib analogs endowed with benzofuran moiety as selective COX-2 inhibitors and the evaluation of their anti-inflammatory activity and ulcerogenic liability in vivo.Figure optionsDownload as PowerPoint slide