Synthesis and biological evaluation of novel 2-(2-arylmethylene)hydrazinyl-4-aminoquinazoline derivatives as potent antitumor agents

Two series of novel 2-(2-arylmethylene)hydrazinyl-4-aminoquinazoline derivatives were synthesized and evaluated for their cytotoxicity against H-460, HT-29, HepG2 and SGC-7901 cancer cell lines in vitro. Most compounds displayed moderate to excellent activity, with IC50 values ranging from 0.015 to 4.09 mu M against all tested cell lines, respectively. The most promising compound 9p (E)-2-(24(1-(2,3-dichlorobenzyl)-1H-imidazol-2-yl)methylene)hydrazinyl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine with IC50 values of 0.031 mu M, 0.015 mu M, 0.53 mu M and 0.58 mu M, which was 4- to 224 times more active than references 10 and Iressa, had emerged as a lead for further structural modifications. (C) 2012 Elsevier Masson SAS. All rights reserved.