Synthesis and biological evaluation of novel 2,4,5-substituted pyrimidine derivatives for anticancer activity

A series of novel 2,4,5-substituted pyrimidine derivatives were synthesized and evaluated for inhibition against the human hepatocellular carcinoma BEL-7402 cancer cell line. Several compounds showed potent inhibition with an IC₅₀ value less than 0.10 μM. Structure–activity relationships for this class of compounds at the 2- and 5-position of the pyrimidine scaffold have been elucidated. The most active compound 7gc showed good inhibition of several different human cancer cell lines with IC₅₀ values from 0.024 to 0.55 μM.