Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt.
Eur J Med Chem. 2010 Apr;45(4):1403-14. doi: 10.1016/j.ejmech.2009.12.041. Epub 2009 Dec 28.
Herein, we report the design, synthesis, and pharmacological properties of a series of substituted benzylidene acetone oxime ether derivatives from the corresponding oxime derivatives. All the newly synthesized compounds were investigated in vivo for their anti-inflammatory activities using carrageenin-induced rat paw oedema model. Among the compounds examined, compounds 5b and 7a showed the highest activity, nearly equivalent to that of the standard drug diclofenac sodium. Hence, they were screened for their analgesic activities using acetic acid-induced writhing model in mice and also, their ulcerogenic effects were studied. Compound 7a was found to possess significant anti-inflammatory and analgesic activities with negligible ulcerogenic effect. Docking study of the synthesized compound 7a into the active site of COX-1 and COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor.
在这里，我们报告了一系列取代苯甲醛缩丙酮肟醚衍生物的设计、合成和药理学性质，这些衍生物是由相应的肟衍生物合成的。所有新合成的化合物都在体内用角叉菜胶诱导的大鼠足肿胀模型进行了抗炎活性研究。在所检查的化合物中，化合物 5b 和 7a 表现出最高的活性，几乎与标准药物双氯芬酸钠相当。因此，它们在小鼠醋酸诱导扭体模型中进行了镇痛活性筛选，同时也研究了它们的致溃疡作用。发现化合物 7a 具有显著的抗炎和镇痛活性，且致溃疡作用可忽略不计。将合成的化合物 7a 对接进入 COX-1 和 COX-2 的活性位点，揭示了与选择性 COX-2 抑制剂 SC-558 相似的结合模式。
