为寻找新型非阿片类中枢镇痛剂,以YX0611-1为先导化合物,设计合成了16个新化合物,结构经1H NMR及HR-MS分析验证。小鼠醋酸扭体法与热板法体内镇痛实验结果表明,化合物2、7、8、9、11和15具有明显的镇痛活性。阿片受体亚型μ、δ、κ的结合实验表明,活性化合物均不作用于上述阿片受体。初步毒性实验和药代动力学实验结果表明,化合物7具有较高的安全性及比YX0611-1更好的药代动力学性质,值得进一步深入研究。 In order to find a new non-opioid analgesic, 16 new compounds were designed and synthesized with YX0611-1 as the lead compound. Their structures were confirmed by 1H NMR and HR-MS analysis. In vivo acetic acid writhing and hot plate analgesic test results show that compounds 2,7,8,9,11 and 15 have significant analgesic activity. Binding experiments of the opioid receptor subtypes μ, δ, κ showed that none of the active compounds acted on the above opioid receptors. The results of preliminary toxicity test and pharmacokinetics show that compound 7 has higher safety and better pharmacokinetic properties than YX0611-1, which deserves further study.