Synthesis and Evaluation of Vascular Endothelial Growth Factor Receptor-2 Inhibitory Activity of 6,7-Dimethoxycinnoline Derivatives

A series of 6, 7-Dimethoxycinnoline derivatives were prepared as vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitors and their activity to inhibit VEGFR-2 and epidermal growth factor receptor (EGFR) were evaluated. The structure-activity studies on compounds screening led to the discovery of a novel series of potent and selective VEGFR-2 inhibitors. Compound 6-(6,7-dimethoxycinnolin -4-yloxy)-N-(4-chlorophenyl)naphthalene-1-carboxamide 7a showed potent VEGFR-2 inhibitory activity and good selectivity against EGFR.