芳烷基苯基哌嗪类衍生物的合成及镇痛活性研究  

Synthesis and analgesic activities of phenyl piperazinyl aralkyl ketone derivatives

作　　者：解鹏[1] 王冠[1] 张桂森 张莉[1] 徐翔清 郭琳[3] 李建其[1] 

机构地区：[1]上海医药工业研究院化学制药新技术中心,上海200437 [2]江苏恩华药业集团有限公司,江苏徐州221009 [3]中国科学院上海药物研究所,上海201203

出　　处：《药学学报》2012年第11期1511-1516,共6页Acta Pharmaceutica Sinica

基　　金："重大新药创制"国家科技重大专项(2009ZX09103-101-802;2012ZX09102101-010)

摘　　要：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。To explore novel non-opioid analgesic agents, 16 compounds were synthesized and their structures were confirmed by IH NMR and HR-MS.YX0611-1 was treated as the leading compound. The results of mice writhing model and hot plate model showed that compounds 2, 7, 8, 9, 11 and 15 had obvious analgesic activities in vivo. The test of affinity to μ、δ、κ receptor displayed that active compounds didn＇t act on opioid receptor. The results of preliminary toxicity and pharmacokinetic tests showed that compound 7 had better safety and pharmacokinetic properties than that of YX0611-1, and it deserved further development.

关 键 词：芳烷基苯基哌嗪类衍生物 非阿片类镇痛 合成 药代动力学 

分 类 号：R916[医药卫生—药学]