Abstract: Molecular docking of 2-[(6-methoxyquinazolin-2-yl)amino]-6-{[(1-phenyl-1H-tetrazol-5-yl)thio]methyl}pyrimidin-4-(3H)-one (DCE-254) was carried out and 14 analogues were designed and synthesized. Analogues Ⅴa~Ⅵh were synthesized using ethyl 4-chloroacetoacetate and 1-phenyl-5-mercaptotetrazole, guanidine hydrochloride, substituted benzoyl chloride and substituted isothiocyanate and so on as raw materials. These compounds were characterized by MS and 1HNMR. Five kinds of DCE-254 analogues with strong methylation inhibition were obtained by the radioactive methylation inhibition assay of H3K27me. Among them, 1-(2-methoxy-5-methylphenyl)-3-(6-oxo-4-{[(1-phenyl-1H-tetrazol-5-yl)thio]methyl}-1,6-dihydropyrimidin-2-ylthiourea (Ⅵf) showed the most active, and the inhibition rate was 77%, which was better than that of DCE-254. Key words: EZH2 methyltransferase; methylation inhibitor; antitumor activities; drug and cosmetic materials