靶向聚ADP核糖聚合酶抑制剂AZD-9574的合成工艺改进  

Improved Synthesis Process Targeting Poly ADP Ribose Polymerase Inhibitor AZD-9574

作　　者：党诗涵 张倩倩 李春 李庶心 王保国[4] 闵清 胡文祥 DANG Shi-han;ZHANG Qian-qian;LI Chun;LI Shu-xin;WANG Bao-guo;MIN Qing;HU Wen-xiang(College of Pharmacy,Hubei University of Science and Technology,Xianning 437100,China;College of Pharmacy,Jiangxi University of Chinese Medicine,Nanchang 330000,China;Suzhou Longbotai Pharmaceutical Co.,Ltd.,Suzhou 215000,China;College of Pharmacy,Jining Medical College,Jining 272000,China;Jingdong Xianghu Microwave Chemistry Union Laboratory of Beijing Shenjian Tianjun Medical Science Research Institute,Beijing 101601,China)

机构地区：[1]湖北科技学院药学院,湖北咸宁1437100 [2]江西中医药大学药学院,江西南昌330000 [3]苏州隆博泰药业有限公司,江苏苏州215000 [4]济宁医学院药学院,山东济宁272000 [5]北京神剑天军医学科学研究院京东祥鹄微波化学联合实验室,北京101601

出　　处：《解放军药学学报》2023年第3期244-248,共5页Pharmaceutical Journal of Chinese People's Liberation Army

摘　　要：目的精简合成工艺,优化原始步骤,对靶向聚ADP核糖聚合酶抑制剂AZD-9574合成工艺进行改进。方法本研究分别以5-溴代吡啶酸甲酯和2-甲基(4-溴-3-氟-2-硝基苯胺)丙酸酯为起始原料,经氟代、取代、氨解、脱保护基、取代、还原环化、氧化、偶联、取代合成目标物靶向聚ADP核糖聚合酶抑制剂。结果对合成中关键步骤反应条件进行了优化,提高了产率。结论该方法操作简便、原料价廉易得、反应条件温和,可用于靶向聚ADP核糖聚合酶抑制剂的大规模制备。Objective To streamline the process and optimize the original steps in order to prepare the targeted poly ADP ribose polymerase inhibitor on a large scale.Methods Methyl 5-bromopiclidinate and 2-methyl(4-bromo-3-fluoro-2-nitroaniline)propionate were used as starting materials,and the targets(targeting poly ADP ribose polymerase inhibitors)were synthesized via fluorination,substitution,ammonilysis,deprotection,substitution,reduction cyclization,oxidation,coupling and substitution.Results The reaction conditions for the key steps of synthesis were optimized and the yield was improved.Conclusion This method is user-friendly and cost-effective,with easily-available raw materials.The reaction conditions are mild,and the process can be used for large-scale preparation of targeting poly ADP ribose polymerase inhibitors.

关 键 词：靶向聚ADP核糖聚合酶抑制剂 合成工艺 

分 类 号：R914.5[医药卫生—药物化学]