Design and synthesis of VEGFR-2 inhibitors based on oleanolic acid moiety.

In this study, twenty-four oleanolic acid (OA) derivatives were rationally designed based on molecule docking studies and their VEGFR-2 inhibitory activities were tested by Homogeneous time-resolved fluorescence (HTRF) method in vitro. All of the synthesized compounds were identified as new compounds, and the structures of these compounds were determined by 1H-NMR and ESI-MS. In the screening for VEGFR-2 inhibitors, compounds I6 and I7 exhibited excellent inhibitory effect. The results indicated that insertion of phenylurea group with a linker at position C-28 of OA can increase the activity against VEGFR-2 significantly. [Formula: see text].