恩杂鲁胺的合成进展  

Advances in the synthesis of enzalutamide

作　　者：孟祥国 庞欣仪 郁思杰 史雨豪 周兆丽 MENG Xiang-guo;PANG Xin-yi;YU Si-jie;SHI Yu-hao;ZHOU Zhao-li(College of Pharmacy,Shanghai University of Medicine and Health Sciences,Shanghai 201318,China;Shanghai Key Laboratory of Molecular Imaging,Shanghai 201318,China)

机构地区：[1]上海健康医学院药学院,上海201318 [2]上海市分子影像重点实验室,上海201318

出　　处：《中国药物化学杂志》2022年第5期399-406,共8页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目(81803581);上海健康医学院2018年协同创新重点专项(SPCI-18-18-003);2018年度上海高校特聘教授(东方学者)岗位计划项目(TP2018080)。

摘　　要：恩杂鲁胺是首个上市的第二代非甾体雄激素受体拮抗剂,用于治疗已扩散或复发的去势抵抗性前列腺癌。随着恩杂鲁胺在前列腺癌治疗中的广泛应用及其对雄激素受体高表达的乳腺癌具有潜在治疗效果的发现,市场对恩杂鲁胺原料药的需求不断增加。因此,研究适用于工业化生产恩杂鲁胺合成方法具有重要的意义。恩杂鲁胺的合成的关键是构建硫代乙内酰脲环,本文以构建硫代乙内酰脲环方法的不同,对恩杂鲁胺的合成方法进行总结,对近十年文献和专利报道的恩杂鲁胺合成方法作以综述。Enzalutamide is the first second-generation non-steroidal androgen receptor(AR) antagonist to be used to treat castration-resistant prostate cancer that has spread or relapsed.With the widespread application of enzalutamide in the treatment of prostate cancer and the high expression of androgen receptor in the potential therapeutic effect of breast cancer, the demand for enzalutamide active pharmaceutical ingredient(API) continue to increase in the market.Therefore, it is of great significance to study the synthetic method which is suitable for industrial production of enzalutamide.This article summarizes the different methods of constructing thiohydantoin ring, and reviews the synthetic methods of enzalutamide in the literatures and patents in the past decades.

关 键 词：恩杂鲁胺 雄激素受体拮抗剂 硫代乙内酰脲 合成 

分 类 号：R914[医药卫生—药物化学]