尼拉帕尼关键中间体的合成研究进展

PROGRESS IN THE SYNTHESIS OF THE KEY INTERMEDIATES OF NIRAPARIB

尼拉帕尼(Niraparib)是一种聚腺苷二磷酸核糖聚合酶1/2(PARP-1和PARP-2)抑制剂类药物。目前报道的合成方法中,以手性3-芳基哌啶和吲唑衍生物偶联合成Niraparib这一方法具有反应条件温和、原子经济性高、适宜放大生产等显著优点。综述了近年来手性3-芳基哌啶及吲唑衍生物的合成进展,重点分析讨论了不同方法合成2个关键中间体的优缺点,为探究更经济、更高效的Niraparib合成方法提供参考。

Niraparib is a poly adenosine diphosphate(ADP)-ribose polymerase 1/2(PARP-1 and PARP-2) inhibitor.Among the currently reported synthetic procedures,the one using the cross coupling of chiral 3-aryl piperidine and indazole derivatives has the advantages of mild reaction conditions,high atomic economy,and suitable scale-up production.The recent development on the synthesis of chiral 3-aryl piperidines and indazole derivatives were summarized,and the advantages or disadvantages of different methods were analyzed.Valuable information for more economical and efficient synthesis of Niraparib was provided.