二芳基取代-1,2,4-三唑类化合物的合成及其抗炎活性研究

以选择性环氧化酶-2(COX-2)抑制剂Celecoxib为先导,根据其构效关系和分子模拟研究结果,应用生物电子等排原理等药物设计方法,设计合成了19个结构全新的二芳基取代-1,2,4-三唑类衍生物,其结构经IR,¹HNMR,MS和元素分析确证.初步的药理试验结果表明,部分目标化合物具有一定的抗炎活性.

Synthesis and Anti-inflammatory Activities of Diarylsubstituted-1,2,4-trizole Derivatives

Nonsteroidal anti-inflammatory durgs(NSAIDs) are among the most widely prescribed medications with their uses limited by significant toxicity.The studies of the cyclooxygenase(COX) show that the side effects of classical NSAIDs come from the inhibition of COX-1,while the therapeutic effects come from the inhibition of COX-2.Selective COX-2 inhibitors were developed as NSAIDs which display the profiles of good potent activities and low side effects. In order to search for the new NSAIDs,using the marketed selective COX-2 inhibitor celecoxib as a leading compound and based on the result of molecular modeling study of COX-2 inhibitors,a series of novel diaryl-substituted-1,2,4-trizole derivatives were designed and synthesized.All the target compounds were confirmed by IR,MS,~1H NMR spectra and elemental analysis.The results of preliminary pharmacological tests in vivo show that some compounds have certain anti-inflammatory effect.