Abstract: The growth of malignant tumors has been shown to be dependent on the evelopment of new blood vessels. Blocking tumor-induced angiogenesis is an efficiency strategy to prevent and cure cancer. It has been shown that the angiogenic process depends on vascular endothelial cell migration and invasion processes regulated by cell adhesion receptor. The integrin α_vβ₃ is such a cell adhesion receptor. Recent studies show the integrin α_vβ₃ and extracellular matrix can recognize each other through Arg-Gly-Asp(RGD) sequence, some peptides containing RGD sequence antagonists can inhibit embryonic neovascularization, tumor-induced angiogenesis, and tumor growth. According to the structure-activity relationships and antiangiogenic mechanism of RGD sequence, we use thalidomide as the leading structure to design and synthesize five 5-carboxy-1,3-dihydro-1,3-dioxo-2H-isoindole derivatives. All of them were first reported and their structures were confirmed by elementary analysis, IR and ¹HNMR spectra. The results of preliminary antiangiogenic tests in vitro showed that most target compounds could inhibit ECV 304 proliferation. Moreover, it has been proved that the inhibition of endothelial cell proliferation was not the result of cytotoxic effect of target compounds.

Key words: RGD sequence, Thalidomide, 1,3-Dihydro-1,3-dioxo-2H-isoindole derivatives, Synthesis, Antiangiogenic activity