芳烷酮哌嗪衍生物的设计合成及镇痛活性  

Design and synthesis of aralkyl-ketone piperazine derivatives and their antalgic activities

作　　者：李建其[1] 黄丽瑛[1] 陈建新[2] 翁志洁[1] 张椿年[1] 

机构地区：[1]上海医药工业研究院,上海200040 [2]中国科学院上海药物研究所,上海201203

出　　处：《药学学报》2007年第11期1166-1175,共10页Acta Pharmaceutica Sinica

摘　　要：以中枢兴奋性氨基酸NMDA受体多胺调节位点为靶点,设计合成芳烷酮哌嗪类全新化合物并研究它们的镇痛活性。哌嗪经甲酰基保护后,与相应的卤代芳烃进行烷基化反应,制备目标化合物。以小鼠扭体法、大鼠热板法、大鼠光热甩尾法等动物体内镇痛模型测试目标化合物的镇痛活性。共合成64个未见文献报道的新化合物,其结构经质谱、核磁共振谱及元素分析确证。镇痛药理试验显示:该类化合物具有较好的镇痛作用及作为新型非阿片类镇痛药开发的潜在价值。化合物I12,I14,I21和I37在三种镇痛模型上均显示很强的镇痛活性,具有深入研究的价值。To synthesize aralkyl-ketone piperazine derivatives as analgesic agents, the N atom of the one side of piperazine ring is protected by formyl group firstly, then the unprotected N atom is alkylated to prepare aralkyl-ketone piperazine derivatives. Their analgesic biological activities were well studied by mice writhing model,rat hot plate model and rat tail flick model. Sixty four compounds were synthesized and pharmacological tests in vivo revealed these compounds have potent analgesic activities, especially compound I12,I14,I21 and I27. These four compounds are more worthy for further research.

关 键 词：芳烷酮哌嗪类化合物 合成 镇痛活性 

分 类 号：R916.2[医药卫生—药学]