SYNTHESIS AND BIOLOGICAL EVALUATION OF NEW PYRIMIDINE DERIVATIVES AS FAK INHIBITORS FOR DEVELOPMENT OF ANTITUMOR AGENTS

In this paper, a set of new pyrimidine derivatives was designed and synthesized. Subsequently, all the final targets were evaluated for antitumor activities in vitro on four human cancer cell lines including U-87 MG, MDA-MB-231, PC-3, and MCF-7, which were high expressed with focal adhesion kinase (FAK). The results were shown that these compounds performed well antitumor activities. Especially 2-((2-((4-((2-((2-acrylamidoethyl)amino)-3,4-dioxocyclobut-1-en-1- yl)amino) phenyl)amino)-5-(trifluoromethyl) pyrimidin-4-yl)amino)-Nmethylbenzamide (7b) exhibited the highest antitumor activities with 2.16 mu M, 2.03 mu M, 6.19 mu M, and 21.31 mu M, respectively. In addition, all the compounds were tested activities against FAK and compound 7b was also the best candidate with IC50 value of 5.9 nM.

Automated summary

A set of new pyrimidine derivatives were designed and synthesized, and evaluated for antitumor activities on cancer cell lines expressing high levels of FAK. The results showed good antitumor activities, with compound 7b exhibiting the highest potency. Additionally, compound 7b also showed strong inhibitory effects against FAK.