Design and synthesis of novel 2-phenyl-5-(1,3-diphenyl-1H-pyrazol-4-yl)-1,3,4-oxadiazoles as selective COX-2 inhibitors with potent anti-inflammatory activity

作者：Bansal Sumit^*; Bala Manju; Suthar Sharad Kumar; Choudhary Shivani; Bhattacharya Shoumyo; Bhardwaj Varun; Singla Sumit; Joseph Alex

来源：European Journal of Medicinal Chemistry, 2014, 80: 167-174.

DOI：10.1016/j.ejmech.2014.04.045

• Pyrazole
• 1,3,4-Oxadiazole
• COX-2
• Anti-inflammatory
• Analgesic
• Molecular docking analysis

A novel series of 2-phenyl-5-(1,3-diphenyl-1H-pyrazol-4-yl)-1,3,4-oxadiazoles were designed and synthesized for selective COX-2 inhibition with potent anti-inflammatory activity. Among the compounds tested, 9g (2-(3-(4-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)-5-phenyl-1,3,4-oxadiazole) was found to be the most potent inhibitor of COX-2 with IC50 of 0.31 mu M showing promising degree of anti-inflammatory activity in the carrageenan-induced rat paw edema model with ED50 of 74.3 mg/kg. The lead compound 9g further showed suppression of acetic acid-induced writhes comparable to that of aspirin and gastrosparing profile superior to the aspirin. Molecular docking analysis displayed higher binding affinity of ligands towards COX-2 than COX-1.

• 出版日期2014-6-10