Design, Synthesis and Antitumor Activity Evaluation of Trifluoromethyl-Containing Polysubstituted Pyrimidine Derivatives

Abstract Design and synthesis of two series of trifluoromethyl-containing polysubstituted pyrimidine derivatives in order to seek more effective anti-tumor drugs, and the antiproliferative activity of these compounds against four human tumor cell lines (PC-3, MGC-803, MCF-7, HGC-27) was evaluated by MTT method. Most of the compounds have moderate anti-proliferative activities, among which compounds ( XXId ) and ( XXIe ) have good selectivity for PC-3 cells. The IC 50 (concentration required to achieve 50% inhibition of the tumor cell proliferation) values of compounds ( XXId ) and ( XXIe ) for PC-3 cell were 4.42 ± 0.46 μmol L –1 and 4.85 ± 0.59 μmol L –1 , respectively, and their anti-proliferative activities were significantly better than that of the positive control 5-fluorouracil (6.39 ± 0.71 μmol L –1 ). Molecular docking results indicated that compounds ( XXId ) and ( XXIe ) were likely to be well integrated in the hydrophobic pocket of ubiquitin-specific protease 7 (USP7), which has the value of further research and development.