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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Synthesis and biological evaluation of azole-diphenylpyrimidine derivatives (AzDPPYs) as potent T790M mutant form of epidermal growth factor receptor inhibitors.
Bioorganic & Medicinal Chemistry 2016 November 2
A series of novel azole-diphenylpyrimidine derivatives (AzDPPYs) were synthesized and biologically evaluated as potent EGFRT790M inhibitors. Among these analogues, the most active inhibitor 6e not only displayed high activity against EGFRT790M/L858R kinase (IC50 =3.3nM), but also was able to repress the replication of H1975 cells harboring EGFRT790M mutation at a concentration of 0.118μmol/L. In contrast to the lead compound rociletinib, 6e slightly reduces the key EGFRT790M-minduced drug resistance. Significantly, inhibitor 6e demonstrates high selectivity (SI=299.3) for T790M-containing EGFR mutants over wild type EGFR, hinting that it will cause less side effects.
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