水杨酰苯胺类mglu5拮抗剂的设计、合成及活性研究  

Design, Synthesis, and Activity Screening of New Potent Mglu5 Receptor Antagonists Based on the Salicylanilide Structure

作　　者：傅榕赓[1] 杨辰枝子 严建业[1] 翁臻 周鑫[1] 李林和[1] 熊广华 廖端芳[1] FU Ronggeng YANG Chenzhizi YAN Jianye WEN-Zhen ZHOU Xin LI Linhe XIONG Guanghua LIAO Duanfang(School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China School of Humanities, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China Hunan Provincial Key Laboratory of Diagnostics of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208,China)

机构地区：[1]湖南中医药大学药学院,湖南长沙410208 [2]湖南中医药大学人文社科学院,湖南长沙410208 [3]国家重点学科国家中医药管理局病理生理实验室,湖南长沙410208

出　　处：《湖南中医药大学学报》2017年第5期489-492,共4页Journal of Hunan University of Chinese Medicine

基　　金：湖南省自然科学基金项目(2015JJ6085);湖南省教育厅资助科研项目(13B080);2015药学湖南省重点学科开放基金项目;2015中医药国际合作专项基金资助项目(ZYGZ201502);湖南中医药大学本科教学质量工程项目(ZY-005)

摘　　要：目的利用骨架跃迁思想设计并合成新型水杨酰苯胺类代谢型谷氨酸受体5(metabotropic glutamate receptor5,mglu5)拮抗剂。方法将取代水杨酸与二取代苯胺缩合得目标化合物Ⅰ-Ⅳ,用核磁共振和质谱进行结构确证,荧光测钙流法进行拮抗mglu5活性测定。结果设计的目标化合物对mglu5具有明显的拮抗活性,其中化合物Ⅰ拮抗活性最好,IC_(50)为0.079μmol/L。结论水杨酰苯胺类化合物为潜在的新型mglu5拮抗剂,值得进一步研究。Objective To design, synthesis and activity screening of salicylanilides as new mglu5 receptor antagonist. Methods A scaffold hopping approach has been exploited to design a novel class of mglu5 receptor antagonists Ⅰ - Ⅳ. The design compounds were synthesized by using salicylic acids and anilines. The structures of target compounds were identified by NMR and MS. The activity of mglu 5 was screened by Ca2x mobilization assay. Results The designed salicylanilides show potent antagonistic activity to mglu5 receptor in vitro. Among them, compound Ⅰ was the best, and IC50 of compound Ⅰ was 0.079 μmol/L. Conclusion The salicylanilides were new potent mglu5 receptor antagonist and worth to be further studied.

关 键 词：水杨酰苯胺 代谢型谷氨酸受体5拮抗剂 骨架跃 

分 类 号：R284.3[医药卫生—中药学] R914.5[医药卫生—中医学]