Vascular　endothelial　growth　factor　receptor-2　(VEGFR-2)　plays　a　crucial　role　in　tumor　angiogenesis,　and　inhibition　of　the　VEGFR-2　signaling　pathway　has　emerged　as　an　attractive　target　for　cancer　therapy.　In　our　effort,　a　novel　series　of　picolinamide-based　derivatives　were　designed　and　synthesized　as　potent　and　effective　VEGFR-2　inhibitors.　All　the　newly　prepared　compounds　were　evaluated　in　vitro　for　their　antiproliferative　activity　against　A549　and　HepG2　cell　lines.　Among　the　new　compounds,　8j　and　8l　exhibited　better　activity　against　both　A549　and　HepG2　cell　lines.　Molecular　docking　was　performed　to　investigate　the　binding　capacity　and　binding　mode　with　VEGFR-2　(PDB　code:　;　4ASD).