N_酰基_4_苯基噻唑_2_胺类衍生物的设计_合成及其乙酰胆碱酯酶抑制活性的研究.pdfVIP

药学学报 Acta Pharmaceutica Sinica 2014, 49 (6): 813?818 · 813 · N-酰基-4-苯基噻唑-2-胺类衍生物的设计、合成及其 乙酰胆碱酯酶抑制活性的研究 马正月, 杨 琦, 张元功, 李俊杰, 杨更亮* (河北大学药学院, 河北省药物质量分析控制重点实验室, 河北 保定 071002) 摘要:以 α-溴代苯乙酮作为原料, 经过 3 步反应, 合成了 N-酰基-4-苯基噻唑-2-胺类化合物。采用 Ellman 分 光光度法测试了化合物对乙酰胆碱酯酶的体外抑制活性, 结果表明, 目标化合物具有一定的乙酰胆碱酯酶抑制 ?1 活性, 其中化合物 8c 的抑制活性最好, 其 IC50 达到了 0.51 μmol·L , 优于利斯的明和石杉碱甲。N-酰基-4-苯基 噻唑-2-胺对乙酰胆碱酯酶的抑制活性值得进一步研究。 关键词: N-酰基-4-苯基噻唑-2-胺; 乙酰胆碱酯酶抑制剂; 阿尔兹海默症 中图分类号: R916 文献标识码: A 文章编号: 0513-4870 (2014) 06-0813-06 Design, synthesis and evaluation of N-acyl-4-phenylthiazole-2-amines as acetylcholinesterase inhibitors MA Zheng-yue, YANG Qi, ZHANG Yuan-gong, LI Jun-jie, YANG Geng-liang* (Key Laboratory of Drug Quality Control of Hebei Province, College of Pharmaceutical Sciences, Hebei University, Baoding 071002, China) Abstract: N-Acyl-4-phenylthiazole-2-amines were designed and synthesized, moreover their effects on acetylcholinesterase activities were tested. N-Acyl-4-phenylthiazole-2-amines were prepared from substituted 2-bromo-1-acetophenones by three steps reaction, and their AChE inhibitory activities were measured by Ellman method in vitro. The results showed that the target compounds had a certain inhibitory activity on AChE ?1 in vitro. Among them, 8c was the best, and IC50 of 8c was 0.51 μmol·L , better than that of rivastigmine and Huperzine-A. The inhibitory activities of N-acyl-4-phenylthiazol