The vascular endothelial growth factor (VEGF) is the main target of tumor treatment. VEGFR-2 is the main functional receptor of VEGF, which is involved in the regulation of angiogenesis. Based on hologram quantitative structure activity relationships (HQSAR) and topomer comparative molecular field analysis (topomer CoMFA), the contribution of 6-amide-2-aryl benzoxazole/benzimidazole derivatives (VEGFR-2 kinase inhibitors) to these structures was discussed and the corresponding modification strategies were proposed. The most effective HQSAR and topomer CoMFA models are generated by using a training set of 33 compounds. In order to ensure the robustness of the model, the randomization test was used, and 11 compounds were selected as the test set. The results show that the q² of cross-validation is 0.646/0.659, and the r² of non-cross-validation is 0.871/0.867, respectively. The data show that both models are reliable. Topomer CoMFA’s steric/electrostatic contour and HQSAR’s atomic contribution map show the structural characteristics controlling its inhibition ability. In addition, molecular docking is also used to study the interaction between these drugs and large proteins, and the ligand pair is connected to the active site of VEGFR-2 kinase, revealing the possible biological active conformation. This study showed that there was a wide interaction between 6-amide-2-aryl benzoxazole/benzimidazole derivatives and Hrg136 and Tyr356 residues of VEGFR-2 kinase active site. Finally, we used ADMET properties and drug-like properties to predict the newly designed molecules, and the results showed that they meet the conditions for becoming drugs and are expected to become potential anti-VEGFR-2 inhibitors. This study can provide a theoretical reference for the synthesis of target products of VEGFR-2 inhibitors.

血管内皮生长因子（VEGF）是肿瘤治疗的主要目标。VEGFR-2是VEGF的主要功能受体，其参与血管生成的调节。基于全息图定量结构活性关系（HQSAR）和拓扑异构体比较分子场分析（拓扑异构体CoMFA），讨论了6-酰胺-2-芳基苯并恶唑/苯并咪唑衍生物（VEGFR-2激酶抑制剂）对这些结构的贡献，并提出了相应的建议。提出了修改策略。最有效的HQSAR和拓扑CoMFA模型是通过使用33种化合物的训练集生成的。为了确保模型的鲁棒性，使用了随机测试，并选择了11种化合物作为测试集。结果表明，q ²交叉验证的值为0.646 / 0.659，而r ²非交叉验证的百分比分别为0.871 / 0.867。数据表明，这两种模型都是可靠的。拓扑CoMFA的空间/静电轮廓和HQSAR的原子贡献图显示了控制其抑制能力的结构特征。此外，分子对接还用于研究这些药物与大蛋白之间的相互作用，并且配体对与VEGFR-2激酶的活性位点相连，揭示了可能的生物学活性构象。这项研究表明6-酰胺-2-芳基苯并恶唑/苯并咪唑衍生物与VEGFR-2激酶活性位点的Hrg136和Tyr356残基之间存在广泛的相互作用。最后，我们使用ADMET特性和类药物特性来预测新设计的分子，结果表明，它们符合成为药物的条件，并有望成为潜在的抗VEGFR-2抑制剂。该研究可为VEGFR-2抑制剂靶标产物的合成提供理论参考。