Vascular　endothelial　growth　factor　receptor-2　(VEGFR-2)　plays　a　crucial　role　in　tumor　angiogenesis,　and　inhibition　of　the　VEGFR-2　signaling　pathway　has　already　become　an　attractive　approach　for　cancer　therapy.　In　this　study,　a　novel　pyrimidine-based　derivative　7j　was　designed　as　lead　compound,　and　three　series　of　potent　VEGFR-2　inhibitors　were　synthesized　and　biologically　evaluated　against　A549　and　HepG2　cell　lines.　Compounds　7d,　9s　and　13n　exhibited　superior　inhibitory　activities　against　A549　cell　with　IC50　ranged　from　9.19　to　13.17　mu　M　and　HepG2　cell　with　IC50　ranged　from　11.94　to　18.21　mu　M　compared　to　those　of　Pazopanib　(IC50　=　21.18　and　36.66　mu　M).　In　addition,　molecular　docking　study　was　performed　to　investigate　the　binding　capacity　and　binding　mode　between　target　compounds　and　VEGFR-2.