【摘要】 目的:寻找具有高镇痛活性的小分子N型钙通道阻断剂。方法:以苄基哌啶酮、芳胺为起始原料,经水解、环合、氢化脱苄等多步反应合成系列化合物,并通过小鼠乙酸扭体模型和N型钙通道电流抑制实验评价化合物的镇痛活性和作用机制。结果:共合成并评价了47个化合物,其中10个化合物具有明显镇痛活性,1个化合物的镇痛活性明显高于阳性化合物。结论:所合成的以螺环为特征的系列化合物具有N型钙通道阻断活性,其中化合物405的电流抑制率为(85±2.7)%,且具有明显的镇痛活性,值得进一步研究。更多还原

【Abstract】 Objective:To discover small molecular N-type calcium channel blockers with high analgesic activities.Methods:Target compounds were synthesized from 1-benzyl-4-piperidone and aromatic amine via several steps.The analgesic activities were evaluated using the mouse acetic acid writhing model and N-type calcium channel current inhibition test.Results:Forty-seven compounds were synthesized and evaluated.The results showed that ten compounds had potent analgesic effectiveness and one compound had more potent analgesic activity than the control compound.Conclusion:Preliminary pharmacological tests show that the spirocyclics compounds synthesized have N-type calcium channel inhibitive activities.The inhibition and analgesic activities of the compound 405 is(85±2.7)%,which can be used as a leading compound for further study.更多还原