Ribociclib琥珀酸盐合成路线图解

Graphical synthetic routes of ribociclib succinate

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.