The development of new highly effective inhibitors of the receptor tyrosine kinases, in particular, receptors of the epidermal growth factor family (EGFR), is an urgent task for the creation of targeted anti-cancer compounds.<br/>There we summarizes the results of molecular modeling, chemical synthesis, and in vitro studies of a number of compounds containing 4-amino-5-(thiazol-2-yl) pyrimidine fragment as a basic scaffold. The cytotoxic effect on the A549 lung cancer cell line, abundantly expressing EGFRwt, has been shown to be at IC50 level 4.39 – 420 μmol and for some compounds, such as ASB1–ASB3, exceeds the cytotoxicity of erlotinib and gefitinib by 5-10 times. In a study on immunofluorescent staining of A549 cells, it was shown that a significant decrease in the expression of phosphorylated signaling kinases pEGFR, pAkt and pERK1 / 2, relative to the EGF-induced control, is particularly high for ASB3.<br/>The obtained results are the starting point for the identification of a new chemotype of inhibitors of receptor kinases of the epidermal growth factor family.

4-Amino-5- (tiazol-2-il) pyrimidine derivatives: New effective inhibitors of EGFR-dependent signal cascades

2019 Spring National Meeting

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