Novel furan 6a-c, furo[2,3-d]pyrimidine 7a-f, 9, 10a-f, 12a,b, 14a-d and furo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine 8a-f derivatives were designed based on their structural similarity to a previously described oxazole VEGFR-2 back pocket binding fragment. The designed compounds were synthesized and screened for their in vitro VEGFR-2 inhibitory activity where they exhibited good to moderate nanomolar inhibition with improved ligand efficiencies. 8b and 10c (IC₅₀ = 38.72 ± 1.7 and 41.40 ± 1.8 nM, respectively) were equipotent to sorafenib and 6a, 6c, 7f, 8a, 8c, 10b, 10f, 12b, 14c and 14d showed good activity (IC₅₀ = 43.31–98.31 nM). The furotriazolopyrimidines 8a-c and furopyrimidine derivative 10c were further evaluated for their in vitro antiproliferative activity against human umbilical vein endothelial cells (HUVECs) where 8b showed higher potency than sorafenib and resulted in cell cycle arrest at G2/M phase whereas 8c revealed good antiproliferative activity with cell cycle arrest at G1 phase. Moreover, 8a-c and 10c showed significant inhibitory effects on the invasion and migration of HUVECs. Molecular docking study was conducted to gain insight about the potential binding mode. The furo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives 8b and 8c represent interesting starting point for antiangiogenic compounds based on their activity and favorable drug likeness profiles.

新颖呋喃6A-C ，呋喃并[2,3- d ]嘧啶7A-F ，9，图10A-F ，图12A，B，14A-d和呋喃并[3,2- ë ] [1,2,4]三唑并[ 1,5 - c ]嘧啶8a-f衍生物是基于它们与先前描述的恶唑VEGFR-2后袋结合片段的结构相似性而设计的。合成并筛选设计的化合物的体外VEGFR-2 抑制活性，其中它们表现出良好到中等的纳摩尔抑制，并具有提高的配体效率。8b和10c (IC ₅₀= 38.72 ± 1.7 和 41.40 ± 1.8 nM）与索拉非尼等效，6a、6c、7f、8a、8c、10b、10f、12b、14c和14d显示出良好的活性（IC ₅₀ = 483M）。进一步评估了呋喃三唑并嘧啶8a-c和呋喃嘧啶衍生物10c对人脐静脉内皮细胞 (HUVEC) 的体外抗增殖活性，其中8b显示出比索拉非尼更高的效力并导致细胞周期停滞在 G2/M 期，而8c显示出良好的抗增殖作用G1 期细胞周期停滞的活性。此外，8a-c和10c对HUVECs的侵袭和迁移有显着的抑制作用。进行分子对接研究以深入了解潜在的结合模式。呋喃[3,2- e ][1,2,4]三唑并[1,5- c ]嘧啶衍生物8b和8c代表了抗血管生成化合物的有趣起点，基于它们的活性和有利的药物相似性特征。