1-(4-Methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazole-3-carboxamides: Synthesis, molecular modeling, evaluation of their anti-inflammatory activity and ulcerogenicity

• A series of novel 1-(4-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazole-3-carboxamides were synthesized.
• Most of the tested compounds exhibited remarkable anti-inflammatory activity.
• In vitro COX-1/COX-2 inhibition studies showed that compounds 4b and 6 are the most potent COX inhibitors.

A series of novel 1-(4-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazole-3-carboxamides were synthesized and confirmed with different spectroscopic techniques. The prepared compounds exhibited remarkable anti-inflammatory activity that represents 38%–100% of indomethacin activity and 44%–115% of celecoxib activity after 3 h. The anilides 5a–l and hydrazide 6 exhibit low incidence of gastric ulceration compared to indomethacin which was confirmed with histopathological investigation. In vitro COX-1/COX-2 inhibition studies showed compounds 4b (COX-1 IC50 = 45.9 μM; COX-2 IC50 = 68.2 μM) and 6 (COX-1 IC50 = 39.8 μM; COX-2 IC50 = 46.3 μM) are the most potent COX inhibitors in the tested compounds. The binding mode for some of the tested compounds to the enzymes was predicted using docking studies.

Compounds 5f and 5i exhibit promising anti-inflammatory activity with safer ulcer indices relative to indomethacin.Figure optionsDownload as PowerPoint slide