螺环类N型钙通道阻断剂的合成及其生物活性  

Design and synthesis of spirocyclics blockers for N-type calcium channel and their biological activities

作　　者：蒋兴凯[1] 恽榴红[1] 张城[1] 吴宁[1] 张树卓[1] 李锦[1] 郑建全[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850

出　　处：《军事医学科学院院刊》2009年第2期101-105,共5页Bulletin of the Academy of Military Medical Sciences

基　　金：国家自然科学基金资助项目(30572249;30371677)

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。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.

关 键 词：N型钙通道 阻断剂 镇痛 

分 类 号：R914[医药卫生—药物化学] R96[医药卫生—药学]