期刊论文

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

中文

湖南中医药大学学报

1674-070X

2017

37

5

489-492

10.3969/j.issn.1674-070X.2017.05.007

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）；

本校为第一机构

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 receptor 5,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,IC50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, compoun...