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以中枢兴奋性氨基酸NMDA受体多胺调节位点为靶点,设计合成芳烷基-4-哌啶醇类全新化合物并研究它们的镇痛活性。以Boc保护的4-哌啶酮或相应取代的4-哌啶酮为原料,在CeCl3/NaI体系的催化下,与相应的α-卤代芳酮进行亲核加成反应等步骤共制备30个未见文献报道的新化合物,经高分辨质谱及核磁共振氢谱确证结构。小鼠扭体法和热板法镇痛试验及阿片受体结合试验结果表明:该类化合物具有较好的镇痛作用,其中化合物8、13、22在两种镇痛模型上均显示很强的镇痛活性,与阿片μ、δ、κ受体无明显亲和力,具有作为非阿片类镇痛新药开发的潜在价值。
Targeting the central excitatory amino acid NMDA receptor polyamine site, new compounds were synthesized and their analgesic activities were studied. Using Boc-protected 4-piperidone or the corresponding substituted 4-piperidone as raw materials, under the catalysis of CeCl3 / NaI system, nucleophilic addition reaction with the corresponding α-halogenated aryl ketone and other steps to prepare 30 A new compound has not been reported in the literature, confirmed by high-resolution mass spectrometry and nuclear magnetic resonance structure. The mice writhing method and hot plate analgesic test and opioid receptor binding test results show that: the compounds have good analgesic effect, of which compound 8,13,22 in both analgesic models showed strong The analgesic activity has no obvious affinity with opiate μ, δ, κ receptors, and has potential value as a new non-opioid analgesic drug.