氟代马蹄金素二肽模拟物的合成及其抗HBV活性初探

Synthesis and anti-HBV activity of fluorinated dipeptidomimetics of Matijin-Su

为拓展马蹄金素(MTS)二肽衍生物结构多样性,以获得新型抗乙肝病毒活性目标分子,本文采用生物电子等排体替换法,将MTS二肽衍生物中容易水解的酰胺键以含有三氟甲基取代的甲氨基单元替换,设计合成了新型氟代MTS二肽模拟物。所有目标化合物均通过^(1)H NMR、^(13)C NMR、^(19)F NMR、HRMS或ESI-MS进行了结构确证,通过单晶X射线衍射测定了化合物10′的晶体结构,并以HepG22.2.15细胞模型对其进行了体外抗乙肝病毒(HBV)测试,结果显示所有目标化合物对HBV DNA的复制均有抑制作用,14e、14f、14k的IC_(50)值分别为0.37、0.29、0.79μmol·L^(-1)。

To expand the structural diversity of Matijin-Su(MTS)derivatives and explore novel anti-HBV activity compounds,a series of fluorinated dipeptidomimetics of MTS were designed and synthesized by using trifluoromethyl substituted methylamine unit as bioisostere to replace the amide bond of the MTS derivatives.The structures of all target compounds were confirmed by ^(1)H NMR,^(13)C NMR,^(19)F NMR,HRMS,or ESI-MS,and the crystal structure of 10'was determined by X-ray single crystal diffraction.Their inhibitory activity against hepatitis B virus(HBV)in vitro were evaluated using HepG22.2.15 cell model.The results showed that all target compounds had inhibitory effect on HBV DNA replication,the IC_(50) of 14e,14f,and 14k were 0.37,0.29,and 0.79μmol·L^(-1),respectively.