Ribociclib琥珀酸盐合成路线图解  

Graphical synthetic routes of ribociclib succinate

作　　者：邓玉晓 任业明 孙晋瑞 段崇刚 林治秘 李丹 冯光玲 DENG Yu-xiao;REN Ye-ming;SUN Jin-rui;DUAN Chong-gang;LIN Zhi-mi;LI Dan;FENG Guang-ling(Shandong Academy of Pharmaceutical Sciences Shandong Provincial Key Laboratory of Chemical Drug,Jinan 250101,China;Shandong Haiyou Freda Pharmaceutical Co.,Ltd.,Linshu 276700,China)

机构地区：[1]山东省药学科学院山东省化学药物重点实验室,济南250101 [2]山东海佑福瑞达制药有限公司,临沭276700

出　　处：《中国新药杂志》2019年第6期677-682,共6页Chinese Journal of New Drugs

摘　　要：Ribociclib琥珀酸盐(商品名:Kisqali)是一种新型细胞周期蛋白依赖性激酶4/6抑制剂,可与芳香酶抑制剂联合用药作为初始内分泌治疗方案,用于绝经后激素受体阳性(HR+)、人类表皮生长因子受体2阴性(Her2-)或转移性乳腺癌的女性患者。本文通过逆合成分析法,将ribociclib切断为4个片段,并对4个片段和ribociclib琥珀酸盐的合成路线进行总结。分析表明,路线3成本低、总收率高、反应条件温和,具有工业化生产前景。Ribocidib succinate, with the brand name of Kisqali, is a novel cyclin-dependent kinase 4/6 inhibitor that can be used in combination with an aromatase inhibitor as initial endocrine-based therapy for postmenopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) or metastatic breast cancers. In this article , ribocidib was cleaved into four fragments by retrosynthetic analysis, and the synthetic routes of the four fragments and ribocidib succinate were summarized. As the analysis shown , the route 3 , with lower cost, a higher total yield , milder reaction conditions, has a more favorable prospect in manufacturing scale.

关 键 词：Ribociclib琥珀酸盐 逆合成分析 合成路线图解 选择性细胞周期蛋白依赖性激酶4/6抑制剂 切断法 

分 类 号：R914.5[医药卫生—药物化学]