莱博雷生的合成研究进展  

Research Progress in the Synthesis of Lemborexant

作　　者：张仲奎 王淑珍 张乃华 鹿晓东 张贵民 ZHANG Zhongkui;WANG Shuzhen;ZHANG Naihua;LU Xiaodong;ZHANG Guimin(National Engineering and Technology Research Center of Chirality Pharmaceutical,Shandong New Time Pharmaceutical Co.,Ltd.,Lunan Pharmaceutical Group Co.,Ltd.,Linyi 273400)

机构地区：[1]鲁南制药集团股份有限公司,山东新时代药业有限公司,国家手性制药工程技术研究中心,山东临沂273400

出　　处：《中国医药工业杂志》2024年第5期612-619,共8页Chinese Journal of Pharmaceuticals

摘　　要：莱博雷生(1)是一种用于治疗失眠症的食欲素受体拮抗药。该药物的化学结构比较复杂,存在2个手性中心及1个环丙烷结构,化学合成有一定的困难。文章从如何构建手性环丙烷的角度,以3-氟苯乙腈(5)、2-溴-5-氟苯乙酸(20)、2-(3-氟苯基)乙酸烯丙酯(23)或3-氟苯乙酸甲酯(30)为起始物料,对1的合成路线进行了分析和总结,并进行了相应的机制解析。Lemborexant(1)is an orexin receptor antagonist drug used for the treatment of insomnia.The chemical structure of this drug is relatively complex,with two chiral centers and a cyclopropane structure,which creates certain difficulties for chemical synthesis.This review analyzes and summarizes the synthesis routes of 1 from the perspective of how to construct chiral cyclopropane,using 3-fluorophenylacetonitrile(5),2-bromo-5-fluorophenylacetic acid(20),allyl 2-(3-fluorophenyl)acetate(23)or methyl 3-fluorophenyl acetate(30)as the starting materials,with corresponding mechanism analysis in the key part and a brief overview of each route.

关 键 词：莱博雷生 失眠症 食欲素受体拮抗药 合成 研究进展 

分 类 号：R971.3[医药卫生—药品] TQ460.6[医药卫生—药学]