DEVELOPMENT OF 5-TRIFLUOROMETHYLPYRIMIDINE DERIVATIVES AS DUAL INHIBITORS OF EGFR AND SRC FOR CANCER THERAPY

In this paper, we reported a new series of 5-trifluoromethylpyrimidine derivatives (4a-4f, 6a-6j) for cancer therapy. They were tested for antitumor activity in vitro on four human cancer cell lines including A549, K562, HepG2, MCF-7 and two kinase including wild type epidermal growth factor receptor tyrosine kinase (EGFR(wt)-TK) and c-Src. The results suggested that some of the compounds (4a, 4b, 4c, 4e, 6b, 6d, 6e, 6f, 6g, 6h) performed well activities. Especially 2-((2-((4-((2-(cyclohexylamino)-3,4-dioxocyclobut-1-en-1-yl)aminophenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)-N-methylbenzamide (6g) showed high antitumor activities against four cancer cell lines with 1.08 mu M, 2.06 mu M, 1.24 mu M and 2.57 mu M, respectively. Furthermore, compound 6g inhibited EGFR(wt) and Src at the values of 0.75 mu M and 0.15 mu M.

Automated summary

In this paper, a new series of 5-trifluoromethylpyrimidine derivatives were reported for cancer therapy. The compounds were tested for antitumor activity and inhibition of kinases. The results showed that some compounds exhibited good antitumor activity, with compound 6g showing high activity against four cancer cell lines and inhibiting the activity of EGFR and Src.