A series of novel substituted 4-anilinoquinazolines and their related compounds were designed and prepared by 3D modeling as potential inhibitors of VEGFR-2. Evaluation of VEGFR inhibitory activities suggested that compound I10 was a more potent (IC₅₀ = 0.11 nM) VEGFR-2 inhibitor than most of the listed drugs. Kinase panel assays demonstrated that compound I10 was the selective VEGFR-2 inhibitor. The prediction of 3D modeling unveiled a unique binding mode of this lead compound to VEGFR-2. Compound I10 exhibited remarkable anti-angiogenesis and anti-proliferation in HUVEC at low nanomolar concentrations. PK studies indicated that the lead compound possessed adequate oral bioavailability in various species. In vivo subcutaneous tumor model demonstrated that oral administration of I10 demonstrated potent efficacy in inhibiting tumor growth and angiogenesis. All these results suggested compound I10 is a potential drug candidate for cancer treatment.

通过3D建模设计和制备了一系列新型取代4-苯胺基喹唑啉及其相关化合物作为VEGFR-2的潜在抑制剂。VEGFR 抑制活性的评估表明，化合物I10是 比大多数列出的药物更有效的 (IC _{50 = 0.11 nM) VEGFR-2 抑制剂。}激酶组测定证明化合物I10是选择性VEGFR-2抑制剂。3D 模型的预测揭示了该先导化合物与 VEGFR-2 的独特结合模式。化合物I10在低纳摩尔浓度下在 HUVEC 中表现出显着的抗血管生成和抗增殖作用。药代动力学研究表明，该先导化合物在不同物种中均具有足够的口服生物利用度。体内皮下肿瘤模型表明，口服I10在抑制肿瘤生长和血管生成方面具有强大的功效。所有这些结果表明化合物I10是治疗癌症的潜在候选药物。