Abstract: A series of oxazole［5, 4-d］pyrimidine derivatives were designed and synthesized to discover novel compounds with antitumor activity. Compounds 8a - 8m were synthesized using acetamidine hydrochloride as the start material. The structures of synthesized compounds were confirmed by IR, ¹H NMR, EI-MS and elemental analysis. The antiangiogenesis activities of the synthesized compounds were determined by MTT in human umbilical vein endothelial cell(HUVEC). The in vitro antitumor activities of the synthesized compounds were determined by MTT assay in A549, HepG2 and U251. Compounds 8c , 8d , 8g , 8i and 8l were found to inhibit the proliferation of all the tested cell lines. Compound 8l exhibited noteworthy activities in A549, HepG2 and U251 cell lines with IC₅₀value lower than the positive reference sunitinib, suggesting that compound 8l might be the promising antitumor agent for further investigation.