Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Bioorg Chem. 2019 Mar;83:47-54. doi: 10.1016/j.bioorg.2018.10.014. Epub 2018 Oct 10.
New pyrazoles and pyrazolo[3,4-b] pyridines were synthesized and their structure was confirmed by elemental analyses as well as IR, H NMR, C NMR, and mass spectral data. All the newly synthesized derivatives were evaluated in vitro for inhibitory activity against COX-1 and COX-2 enzymes and their IC values were calculated, most of the derivatives showed good inhibitory activity with derivatives IVb, IVh and IVJ showing inhibitory activity better than celecoxib. Moreover, the eight most potent derivatives IVa, IVb, IVc, IVd, IVe, IVh, IVJ, and IVL were selected for in vivo assay to measure their effect on paw edema in rates and their ulcerogenic effect. Compounds IVa, IVb and IVc were found to be the most active and selective as COX-2 inhibitors and most effective in protection from edema, they were also found to have lowest ulcerogenic effect among all derivatives.
新的吡唑和吡唑并[3,4-b]吡啶被合成，并通过元素分析以及 IR、H NMR、C NMR 和质谱数据确认其结构。所有新合成的衍生物都在体外评估了对 COX-1 和 COX-2 酶的抑制活性，并计算了它们的 IC 值，大多数衍生物表现出良好的抑制活性，其中衍生物 IVb、IVh 和 IVJ 的抑制活性优于塞来昔布。此外，选择了八个最有效的衍生物 IVa、IVb、IVc、IVd、IVe、IVh、IVJ 和 IVL 进行体内试验，以测量它们对大鼠足肿胀的影响及其致溃疡作用。发现化合物 IVa、IVb 和 IVc 作为 COX-2 抑制剂最有效且选择性最高，并且在防止水肿方面最有效，它们在所有衍生物中的致溃疡作用也最低。
