Microwave-assisted synthesis and pharmacological screening of some triazolothiadiazole derivatives

In this study, twenty-two new [1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles (5a-n, 6a-h) were synthesized under microwave irradiation (MWI). The chemical structures of the compounds were elucidated by their IR, 1H-NMR, LC-MS, and elemental analysis. The compounds were tested for antinociceptive activity by using the tail clip, tail flick, hot plate, and writhing methods in mice. The varying levels of antinociceptive activity of the compounds were compared with those of aspirin. Among these compounds, compound 5g and 5j were found to be significantly more active than the other compounds and the standard in the tests. Also, inhibitory effects of the test compounds on COX-1 and COX-2 activities were investigated. DuP-697 for COX-2 and SC-560 for COX-1 were used as reference standards.

本研究通过微波辐照（microwave irradiation, MWI）合成了22种新型[1,2,4]三唑并[3,4-b][1,3,4]噻二唑类化合物（5a-n、6a-h）。采用红外光谱（IR）、氢核磁共振谱（1H-NMR）、液相色谱-质谱联用（LC-MS）及元素分析对所有化合物的化学结构进行了确证。通过小鼠体内夹尾法、甩尾法、热板法及扭体法测试了受试化合物的镇痛活性，并将各化合物的镇痛活性水平与阿司匹林进行对比。实验结果显示，相较于其余受试化合物及阳性对照阿司匹林，化合物5g与5j的镇痛活性显著更强。此外，本研究还考察了受试化合物对环氧合酶-1（cyclooxygenase-1, COX-1）与环氧合酶-2（cyclooxygenase-2, COX-2）活性的抑制作用，选用DuP-697与SC-560分别作为COX-2与COX-1的参比标准品。