EGFR别构抑制剂BDTX189的合成工艺研究  

Study on the synthesis of EGFR allosteric inhibitor BDTX189

作　　者：汪祖练 袁昕 唐春雷 WANG Zulian;YUAN Xin;TANG Chunlei(School of Life Science and Health Engineering,Jiangnan University,Wuxi 214122,China)

机构地区：[1]江南大学生命科学与健康工程学院,江苏无锡214122

出　　处：《中国药物化学杂志》2025年第1期18-22,共5页Chinese Journal of Medicinal Chemistry

基　　金：江苏省前瞻性联合研究项目(BY2015019-25)。

摘　　要：目的 改进表皮生长因子受体酪氨酸激酶抑制剂BDTX189的合成路线。方法 以7-氟-6-硝基喹唑啉-4(3H)-酮为起始原料,经亲核取代反应得到中间体4-氯-7-氟-6-硝基喹唑啉(3),3经亲核取代反应、Williamson成醚反应、硝基还原反应、亲核取代反应合成目标化合物BDTX189。结果与结论目标化合物及关键中间体的结构经MS、1H-NMR谱确证,总收率为48.2%,纯度为99.36%(HPLC面积归一化法)。相比于文献路线,新路线优化了合成步骤,操作更加简便,同时提高了收率,为BDTX189及其衍生物的合成工艺研究和工业化生产提供了参考。Epidermal growth factor receptor tyrosine kinase inhibitors(EGFR TKIs) play an important role in cell proliferation, differentiation and apoptosis.BDTX189 is an EGFR/HER2 dual-target allosteric inhibitor developed by Black Diamond Therapeutics.In this study, the original synthetic route to BDTX189 was improved by using 7-fluoro-6-nitroquinazolin-4(3H)-one as raw material.The total yield was 48.2% and the purity was 99.36%.The structure of BDTX189 was confirmed by ~1H-NMR and ESI-MS.Compared with the route in the literature, this process optimized the experimental steps, reduced the synthesis cost, was simple to operate and provided a theoretical reference for the synthesis of BDTX189 and its derivatives.

关 键 词：BDTX189 表皮生长因子受体酪氨酸激酶抑制剂 工艺改进 

分 类 号：R914[医药卫生—药物化学]