Novel VEGFR-2 inhibitors with anN-acylhydrazone scaffold

Vascular endothelial growth factor receptor 2 (VEGFR-2) is a tyrosine kinase that mediates a large number of cell responses associated with angiogenesis. The control of the angiogenic pathway in tumorigenesis by the inhibition of VEGFR-2 is considered a promising therapeutic strategy for the prevention and control of solid tumor growth. In this study, the design, synthesis, and biological evaluation of a novel series of VEGFR-2 inhibitors with anN-acylhydrazone (NAH) scaffold (9a-h) are reported. The molecular design is validated by docking studies and by in vitro inhibitory activity assays. Compounds9b,9c,9d, and9feffectively inhibited neovascularization induced by VEGF in the chorioallantoic membrane assay. Thus, these NAH derivatives are promising antiangiogenic prototypes.