【摘要】 目的 设计合成一类新型c-Met/VEGFR-2双靶点抑制剂，并分别评价其对c-Met和VEGFR-2的抑制活性，探讨初步构效关系，为后续相关研究提供参考。方法 以化合物HBST144为基础，通过生物电子等排等方法，设计、合成新型c-Met/VEGFR-2双靶点抑制剂，采用均相时间分辨荧光法测定化合物对激酶的抑制活性。结果与结论共合成了8个新化合物，其结构均经¹H-NMR、¹³C-NMR和HR-MS确证。抑酶活性结果表明化合物31e具有较强的c-Met和VEGFR-2激酶抑制活性，IC₅₀值分别为0.062μmol·L^-1和0.061μmol·L^-1,可作为优选化合物进行深入研究。更多还原

【Abstract】 With compound HBST144 as the lead compound, eight dual c-Met/VEGFR-2 inhibitors were designed, synthesized and evaluated for antitumor activities to study their preliminary SARs.The target compounds were prepared through different methods with mild conditions and high yields.The structures of the target compounds were identified by ¹H-NMR,¹³C-NMR and HR-MS.The results of biological evaluation indicated that compound 31e showed great potent inhibitory activities against both c-Met and VEGFR-2 with IC₅₀ values of 0.062 μmol·L^-1 and 0.061 μmol·L^-1,respectively, which was worthy of further study.更多还原