Abdellatif Khaled R A, Abdelgawad Mohamed A, Elshemy Heba A H, Alsayed Shahinda S R, Kamel Gehan
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni Suef, 62514, Egypt.
Department of Pharmacology, Faculty of Veterinary, Cairo University, Cairo, Egypt.
Arch Pharm Res. 2015 Nov;38(11):1932-42. doi: 10.1007/s12272-015-0606-7. Epub 2015 Apr 23.
A novel series of 2-pyrazoline derivatives 13a-l was synthesized via aldol condensation of 4-substituted acetophenones with appropriately substituted aldehydes followed by cyclization of the formed chalcones with 4-hydrazinobenzenesulfonamide hydrochloride. The chemical structures of the target pyrazoline derivatives were proved by means of IR, (1)H NMR, (13)C NMR, mass spectroscopy and elemental analyses data. All the synthesized compounds were evaluated for their cyclooxygenase selectivity, anti-inflammatory and ulcerogenic liability. While compounds 13e, 13h and 13i showed moderate COX-2 selectivity in vitro and good anti-inflammatory activity in vivo, compound 13i showed the highest anti-inflammatory activity that is very close in potency to the reference drug (celecoxib) with better gastric profile than celecoxib.
通过4-取代苯乙酮与适当取代的醛进行羟醛缩合反应，然后将生成的查耳酮与4-肼基苯磺酰胺盐酸盐环化，合成了一系列新型的2-吡唑啉衍生物13a-l。通过红外光谱、（1）H核磁共振、（13）C核磁共振、质谱和元素分析数据证实了目标吡唑啉衍生物的化学结构。对所有合成的化合物进行了环氧化酶选择性、抗炎和致溃疡作用的评估。虽然化合物13e、13h和13i在体外表现出中等的COX-2选择性，在体内具有良好的抗炎活性，但化合物13i表现出最高的抗炎活性，其效力与参考药物（塞来昔布）非常接近，且胃安全性优于塞来昔布。
