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

作者：Abdel Aziz Mohamed; Beshr Eman A; Abdel Rahman Islam M; Ozadali Keriman; Tan Oya Unsal; Aly Omar M^*

来源：European Journal of Medicinal Chemistry, 2014, 77(2): 155-165.

DOI：10.1016/j.ejmech.2014.03.001

• 1,2,4-Triazole
• Anti-inflammatory
• Ulcerogenicity
• Histopathological investigation
• Cyclooxygenase activity
• Docking study

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-1 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 mu M; COX-2 IC50 = 68.2 mu M) and 6 (COX-1 IC50 = 39.8 mu M; COX-2 IC50 = 46.3 mu M) 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.

• 出版日期2014-4