Der Pharma Chemica
Journal for Medicinal Chemistry, Pharmaceutical Chemistry, Pharmaceutical Sciences and Computational Chemistry


Synthesis, Cyclooxygenase Inhibition, Anti-inflammatory Evaluation and Gastric Liability of Some Novel Indole Derivatives as Selective COX-2 Inhibitors

Author(s): Khaled RA Abdellatif, Mohammed T Elsaady, Noha H Amin, Ahmed A Hefny

A new group of (4-substitutedphenyl)(3-((2-(4-substitutedphenyl)hydrazono)methyl)-1H-indol-1-yl)-methanone derivatives 13a-f as indomethacin analogs was synthesized through N-benzoylation of indole-3-cabaldehyde with the appropriate benzoyl fragment followed by reaction with substituted phenylhydrazine. All the synthesized compounds were evaluated in vitro for Cyclooxygenase (COX-1/COX-2) inhibitory activity and in vivo for their anti-inflammatory activity in comparison with the parent drug indomethacin. Compounds 13a, b, d, e which, contain SO2Me or SO2NH2 group as a pharmacophore of COX-2, exhibited the most anti-inflammatory and selectivity actives so, they were more evaluated by calculating their ED50% doses and ulcerogenic indices to ensure their gastric safety margin relative to indomethacin.