Design, synthesis and biological evaluation of type-II VEGFR-2 inhibitors based on quinoxaline scaffold

• Quinoxaline based compounds were synthesized as VEGFR-2 inhibitors.
• Molecular modeling study was conducted for the target compounds on VEGFR-2.
• Compound IX displayed the best inhibition percent againstVEGFR-2 which is 69%.
• Compound VIIa displayed the best IC50 value of 10.27 μM.

In an effort to develop ATP-competitive VEGFR-2 selective inhibitors, a series of new quinoxaline-based derivatives was designed and synthesized. The target compounds were biologically evaluated for their inhibitory activity against VEGFR-2. The design of the target compounds was accomplished after a profound study of the structure activity relationship (SAR) of type-II VEGFR-2 inhibitors. Among the synthesized compounds, 1-(2-((4-methoxyphenyl)amino)-3-oxo-3,4 dihydroquinoxalin-6-yl)-3-phenylurea (VIIa) displayed the highest inhibitory activity against VEGFR-2. Molecular modeling study involving molecular docking and field alignment was implemented to interpret the variable inhibitory activity of the newly synthesized compounds.

Figure optionsDownload as PowerPoint slide