Design, synthesis and in vitro antitumor activity of 4-aminoquinoline and 4-aminoquinazoline derivatives targeting EGFR tyrosine kinase

Two series of new 6-alkoxy-4-substituted-aminoquinazolines (2-4f) and their bioisoteric quinoline congeners (5-7c) were designed and synthesized. Virtual screening was carried out through docking the designed compounds into the ATP binding site of epidermal growth factor receptor (EGFR) to predict if these compounds have analogous binding mode to the EGFR inhibitors. The newly synthesized compounds were tested in vitro on human breast carcinoma cell line (MCF-7) in which EGFR is highly expressed. Most of the tested compounds exploited potent antitumor activity with IC50 values in the nanomolar range in particular compound 3b which displayed the highest activity among the tested compounds with IC50 equal to 0.13 nmol. (C) 2008 Elsevier Ltd. All rights reserved.