水杨酰苯胺类mglu5拮抗剂的设计、合成及活性研究

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.

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

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 Ca2+ 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.