School of Pharmaceutical Sciences, Shoolini University, Solan, Himachal Pradesh, India.
School of Pharmaceutical Sciences, Jaipur National University, Jaipur 302017, India.
Eur J Med Chem. 2014 Jun 10;80:167-74. doi: 10.1016/j.ejmech.2014.04.045. Epub 2014 Apr 15.
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 μM 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 gastro-sparing profile superior to the aspirin. Molecular docking analysis displayed higher binding affinity of ligands towards COX-2 than COX-1.
我们设计并合成了一系列新型的 2-苯基-5-(1,3-二苯基-1H-吡唑-4-基)-1,3,4-恶二唑，以选择性抑制 COX-2，同时具有很强的抗炎活性。在所测试的化合物中，化合物 9g（2-(3-(4-硝基苯基)-1-苯基-1H-吡唑-4-基)-5-苯基-1,3,4-恶二唑）对 COX-2 的抑制作用最强，IC50 为 0.31 μM，在角叉菜胶诱导的大鼠足肿胀模型中显示出有希望的抗炎活性，ED50 为 74.3 mg/kg。先导化合物 9g 进一步显示出对醋酸诱导的扭体的抑制作用与阿司匹林相当，并且具有优于阿司匹林的胃保护作用。分子对接分析显示配体对 COX-2 的结合亲和力高于 COX-1。
