Abstract

This manuscript describes the synthesis of novel indole derivatives as indomethacin analogues. The synthesized compounds 13a-f were evaluated for their anti-inflammatory activity, COX-2 selectivity and ulcerogenic liability in comparison with reference drug indomethacin. Among synthesized compounds, compounds containing COX-2 pharmacophore moiety SO2Me or SO2NH2 such as 13a,d or 13b,e respectively which exhibited higher anti-inflammatory activity and COX-2 selectivity and safer gastric profile than that containing Me group 13c,f. Molecular docking study was performed for compounds 13d,e to ensure biological results in relative with valdecoxib which is one of the most COX-2 selective inhibitor. Docking studies showed good selectivity of synthesized compounds compared with valdecoxib.

Key words: NSAIDs; Cyclooxygenase; Indomethacin; Anti-inflammatory activity; Ulcerogenicity.