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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 find a small molecule N-type calcium channel blocker with high analgesic activity. Methods: Benzylpiperidone and aryl amine were used as starting materials to synthesize a series of compounds via hydrolysis, cyclization and dehydrogenation. The effects of acetic acid writhing model and N type calcium channel current inhibition were evaluated Analgesic activity and mechanism of action of compounds. RESULTS: Forty-seven compounds were synthesized and evaluated. Ten compounds showed significant analgesic activity, and the analgesic activity of one compound was significantly higher than that of the positive compounds. CONCLUSION: The compounds characterized by spiro ring have N-type calcium channel blocking activity. The inhibitory rate of current of compound 405 is (85 ± 2.7)%, and has obvious analgesic activity, which deserves further study.