ABT-199的合成方法评述

The Review to the Synthesis Method of ABT-199

ABT-199(Venetoclax)为全球首个选择性蛋白-蛋白相互作用B细胞淋巴瘤因子-2选择性抑制剂,目前已经获准在美国FDA和欧盟上市,批准用于治疗携带17p删除突变以及之前已接受至少一种疗法的慢性淋巴细胞白血病。本文综述了迄今为止文献报道的Venetoclax的3条合成工艺路线,并进行了相应的评价。通过对这些合成工艺路线在反应条件、放大可行性、收率、安全性、是否使用重金属和成本等方面进行的比较和分析,葛敏报道的汇聚合成具有较好的工业化前景。

ABT （Venetoclax） is the first PPI selective inhibitor of B-cell lymphoma-2 in the world, and has been approved by FDA and EU for treating relapsed or refractory chronic lymphocytic leukemia patients with 17p deletion who have received at least one prior therapy. In this paper, three reported synthesis routes of ABT-199 were reviewed and compared in the reaction conditions, robust feasibility, overall yield, process safety whether use of heavy metal and cost. Finally, we found the last convergent strategies from Min Ge has the greatest potential for industrialization.