Study on the synthesis and antitumor activities of 2,4-diarylaminopyrimidines
Epidermal growth factor receptor(EGFR)is a transmembrane receptor tyrosine kinase.The EGFR family plays an essential role in normal organ development by mediating morphogenesis and differentiation.Unlike normal cells that have tight regulatory mechanisms controlling EGFR pathways,tumor cells often have dysregulated EGFR signaling through receptor overexpression and mutation.EGFR inhibitors like osimertinib,bearing 2,4-diarylaminopyrimidine moiety,showed potent and selective EGFR inhibitory activities.For increasing the antitumor activity,fifteen 2,4-diarylaminopyrimidine derivatives were designed and synthesized using osimertinib as lead compound,from o-phenylenediamine via six-step reactions including nuleophilic substitution,reduction and acylation.The structures of the target compounds were confirmed by 1H-NMR and ESI-MS.The in vitro anti-proliferative effects of the target compounds on A549 cells were determined by MTT assay.Preliminary pharmacological results showed that the introduction of halogen atom at the C5 position of pyrimidinyl moiety can improve the antiproliferative effect.
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