武汉工程大学学报2024，Vol.46Issue(4)：355-362,8.DOI:10.19843/j.cnki.CN42-1779/TQ.202406006
阿托吉泮的合成研究进展
Research progress in synthesis of atogepant
摘要
Abstract
Atogepant,a calcitonin gene-related peptide receptor antagonist,is the first oral drug in the world for the prophylactic treatment of migraines in adults.It is prepared by the condensation reaction of two key chiral intermediates,an amino-piperidone derivative(Intermediate 2)and a carboxylic acid(Intermediate 3).The synthetic routes of these two intermediates are reviewed based on different starting materials and synthetic processes.All reported synthetic routes use chiral resolution methods;among the five synthetic routes of Intermediate 2,the optimal route Ⅴ uses chiral resolution reagents;among the three synthetic routes of Intermediate 3,although the optimal route Ⅲ uses cheap and readily available raw materials and has a high yield,the repeated use of the Grignard reaction requires more robust equipment and harsh operating conditions.The asymmetric synthesis methods and synthetic process research of these two intermediates,as well as the continuous flow synthesis process research of atogepant,will be important directions to improve the safety and yield of the synthetic process of this drug.关键词
阿托吉泮/受体拮抗剂/偏头痛/关键中间体/合成路线Key words
atogepant/receptor antagonist/migraine/key intermediates/synthetic routes分类
医药卫生引用本文复制引用
张锋,肖梦鑫,张双双,龙姣,朱园园,廖杰,古双喜..阿托吉泮的合成研究进展[J].武汉工程大学学报,2024,46(4):355-362,8.基金项目
国家自然科学基金(22377097、22074114) （22377097、22074114）
湖北省教育厅科学技术研究计划中青年人才项目(Q20221513) （Q20221513）
湖北省自然科学基金(2024AFB233) （2024AFB233）
