Both c-Met and VEGFR-2 are important targets for cancer therapies. Here we report a series of potent dual c-Met and VEGFR-2 inhibitors bearing thieno[2,3-d]pyrimidine scaffold. The cell proliferation assay in vitro demonstrated that most target compounds had inhibition potency both on c-Met and VEGFR-2 with IC₅₀ values in nanomolar range, especially compound 12j and 12m. Based on the further enzyme assay in vitro, compound 12j was considered as the most potent one, the IC₅₀ values of which were 25 nM and 48 nM for c-Met and VEGFR-2, respectively. Following that, we docked the compound 12j with the proteins c-Met and VEGFR-2, and interpreted the SAR of these analogues. All the results indicate that 12j is a dual inhibitors of c-Met and VEGFR-2 that holds promising potential.

c-Met和VEGFR-2都是癌症治疗的重要靶标。在这里，我们报告一系列有效的双重c-Met和VEGFR-2抑制剂，带有噻吩并[2,3- d ]嘧啶骨架。体外细胞增殖试验表明，大多数目标化合物对c-Met和VEGFR-2均具有抑制作用，IC ₅₀值在纳摩尔范围内，尤其是化合物12j和12m。根据进一步的体外酶分析，化合物12j被认为是最有效的化合物，其c-Met和VEGFR-2的IC ₅₀值分别为25 nM和48 nM。之后，我们将化合物12j停靠与蛋白质c-Met和VEGFR-2结合，并解释了这些类似物的SAR。所有结果表明，12j是c-Met和VEGFR-2的双重抑制剂，具有广阔的发展前景。