Discovery of 2-Anilinopyrimidine-based Selective Inhibitors against Non-small Cell Lung Cancer Cell Line H1975

Small molecular EGFR-tyrosine kinase inhibitors (EGFR-TKIs) have been proved as a successful and powerful strategy for the treatment of non-small-cell lung cancer (NSCLC). Recent studies have reported that the T790M mutation in EGFR is the most prevalent factor in acquired resistance for NSCLC patients. In an effort to identify small molecules for the inhibition of T790M mutant EGFR, a screening of our in-house chemical library was conducted by an MTT assay. A set of 2-anilinopyrimidine derivatives was rationally selected and then evaluated for their antiproliferative activities against three different type of NSCLC cell lines H358 (EGFR wild-type), HCC827 (EGFR exon 19 deletion) and H1975 (EGFR L858R/T790M double-mutant). Compounds 9, possessing a piperidine in the part A and a 4-methylpiperidine in the part B, selectively showed inhibitory activity in the T790M mutant cell line. In addition, in silico studies of 9 utilizing a SwissADME tool exhibited good drug-like properties.