Aurora-B激酶抑制剂AZD1152-HQPA的合成  

Synthesis of Aurora-B Kinase Inhibitor AZD1152-HQPA

作　　者：王丽丽 王兴兰 马才玉 程飞 毛远湖 汤磊 张吉泉 WANG Li-li;WANG Xing-lan;MA Cai-yu;CHENG Fei;MAO Yuan-hu;TANG Lei;ZHANG Ji-quan(School of Medicine and Health Management,Guizhou Medical University,Guizhou Guiyang 550025;College of Pharmacy,Guizhou Medical University,Guizhou Guiyang 550025,China)

机构地区：[1]贵州医科大学医药卫生管理学院,贵州贵阳550025 [2]贵州医科大学药学院,贵州贵阳550025

出　　处：《广州化工》2020年第8期29-31,共3页GuangZhou Chemical Industry

基　　金：贵州省科技支撑计划项目(黔科合[2016]支撑2819);贵州省自然科学基金资助项目(贵黔合基础[2020]1z073);州省卫生健康委科技基金(gzwjkj2019-1-179);贵阳市科技基金(筑科合[2017]30-28号);贵州省大学生创新计划项目(2018520355,20195200128)。

摘　　要：AZD1152-HQPA是Aurora-B激酶选择性抑制剂AZD1152(Barasertib)的前体,具有喹唑啉母核。本研究对其合成路线进行优化。以2-氨基-4-氟苯甲酸为起始原料,经环合、取代、氯代、氨化、酰胺化以及最后取代等六步反应得到Aurora-B选择性激酶抑制剂AZD1152-HQPA,总收率27.6%,产物纯度大于99%。通过对酰胺化缩合条件的优化,使得整条合成路线原料便宜易得、反应操作简便,且成本更低,适合AZD1152-HQPA的放大合成。AZD1152-HQPA is the prodrug of Aurora-B kinase selective inhibitor AZD1152(Barasertib) bearing a quinazoline scaffold and this study presents the optimization of the synthetic route. Starting from 2-amino-4-fluorobenzoic acid, AZD1152-HQPA was synthesized via cyclization, substitution, chloridization, ammoniation, amidation and final substitution. The title compound was obtained with a total yield of 27.6% and purity of more than 99%. The optimization of the amidating condensation reaction made this synthetic route more materials-accessible, operations-handy and cost-effective, and it was suitable for the scale-up preparation of AZD1152-HQPA.

关 键 词：肿瘤 AURORA激酶抑制剂 喹唑啉 酰胺化 合成 

分 类 号：R914.5[医药卫生—药物化学]