Ragab Fatma Abdel-Fattah, Abdel-Gawad Nagwa Mohamed, Georgey Hanan Hanna, Said Mona Fikry
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Chem Pharm Bull (Tokyo). 2013;61(8):834-45. doi: 10.1248/cpb.c13-00314.
Some 1-(4-chlorophenyl or benzenesulfonamide)-2,3- and/or 4-substituted-1H-pyrazol-5(4H)-one derivatives were synthesized and screened for their anti-inflammatory and analgesic activities, in addition to their ulcerogenic liability. They were found to be active as anti-inflammatory and analgesic agents. Compound 6b was found to be the most active as anti-inflammatory agent and compound 9b was found to be the most active one as anti-inflammatory and analgesic agent. On the other hand, cyclooxygenase-1/-2 (COX-1)/COX-2 isozyme selectivity was also done and the tested compounds showed equal inhibition to both isoforms. Moreover, 2D-quantitative structure-activity relationship (QSAR) studies revealed well predictive and statistically significant and cross validated QSAR model that helps to explore some expectedly potent compounds.
合成了一些1-(4-氯苯基或苯磺酰胺)-2,3-和/或4-取代的1H-吡唑-5(4H)-酮衍生物，并对其抗炎、镇痛活性以及致溃疡倾向进行了筛选。发现它们具有抗炎和镇痛作用。化合物6b被发现是最具活性的抗炎剂，化合物9b被发现是最具活性的抗炎和镇痛剂。另一方面，还进行了环氧化酶-1/-2（COX-1）/COX-2同工酶选择性研究，测试的化合物对两种同工型均表现出同等抑制作用。此外，二维定量构效关系（QSAR）研究揭示了具有良好预测性、统计学显著性且经过交叉验证的QSAR模型，有助于探索一些预期的强效化合物。
