新型NK1受体拮抗剂的合成及生物活性研究  

Synthesis and bioactivity of novel NK1 receptor antagonists

作　　者：和龙 向洪刚 刘新琦 温晓燕 王玲 欧阳亮[2] 何俊[2] HE Long;XIANG Honggang;LIU Xinqi;WEN Xiaoyan;WANG Ling;OU YANG Liang;HE Jun(Beijing Funhau Medicine Technology Co. ,Ltd. ,Beijing,102600 P. R. China;State Key Laboratory of Biotherapy and Cancer Center,West China Hospital,Sichuan University,Chengdu,Sichuan,610041 P. R. China)

机构地区：[1]北京宽厚医药科技有限公司,北京102600 [2]四川大学华西医院生物治疗国家重点实验室,四川成都610041

出　　处：《华西药学杂志》2019年第4期332-336,共5页West China Journal of Pharmaceutical Sciences

基　　金：四川省应用基础研究项目(2019YJ0108);川大-泸州战略合作基金(2015CDLZ-S10)

摘　　要：目的制备一类新型N-甲基-N-(4-(2-苯甲基)-6-(4-甲基-1-哌嗪基)-3-吡啶基)苯甲酰胺衍生物,并评价其对NK1受体的体外拮抗活性。方法以6-(4-甲基-1-哌嗪基)-4-(2-甲基苯基)烟酰胺为起始原料,经过霍夫曼降解、酰胺还原和N-酰化等化学反应得到目标化合物;采用钙流实验,在HEK293/NK1R细胞株上进行体外对NK1受体拮抗活性的测定。结果制备了13个新型化合物(Ⅰ1~Ⅰ13),并经1HNMR确证结构。化合物Ⅰ12对HEK293/NK1R细胞有较好的NK1受体拮抗活性。结论化合物Ⅰ12作为一类新型NK1受体拮抗剂,具有深入研究的价值。OBJECTIVE To synthesize a novel series of N-methyl - N- 4-(2-methyl phenyl)-6-(4-methyl-1 -piperazine)-3 - pyridyl benzamide derivatives and to evaluate their antagonistic activity of NK1 receptor in vitro. METHODS The target compounds were synthesized from 6 -(4 - methyl - 1 -piperazin - 1 - yl)- 4 - o - tolyl-nicotinamide by Hoffman degradation, amide reduction and N - acylation. The antagonistic activity of NK1 receptor in vitro of these compounds was measured by calcium flow assay on HEK293/NK1R cell lines. RESULTS Thirteen new compounds (I1- I13) were prepared, and the chemical structures were confirmed by 1 HNMR. Compound I12 exhibited good antagonistic activity of NK1 receptor against HEK293/NK1R cells. CONCLUSION Compound I12 is a valuable NK1 receptor antagonist for further studies.

关 键 词：N-甲基-N-(4-(2-苯甲基)-6-(4-甲基-1-哌嗪基)-3-吡啶基)苯甲酰胺衍生物 合成 生物活性 NK1受体 钙流实验 HEK293/NK1R细胞株 拮抗活性 

分 类 号：R914[医药卫生—药物化学]