Novel Dithiocarbamic Acid Esters Derived from 6-Aminomethyl-4-anilinoquinazolines and 6-Aminomethyl-4-anilino-3-cyanoquinolines as Potent EGFR Inhibitors

Abstract Two series of dithiocarbamic acid esters, 4‐anilinoquinazoline‐6‐ylmethylcarbamodithioic acid esters and 3‐cyano‐4‐anilinoquinolin‐6‐ylmethylcarbamodithioic acid esters, were designed and synthesized. The effect of the synthesized compounds on cell proliferation was evaluated by MTT assay against three human cancer cell lines: MDA‐MB‐468, SK‐BR‐3 and HCT‐116. Most of the compounds are equally or more potent than the positive control lapatinib. Three compounds ( 14d , 14h and 14i) were identified as dual inhibitors of the EGFR and ErbB‐2 kinases and two compounds ( 14b and 14c) were identified as multi‐target kinase inhibitors, and they are very worthy of further study. Installation of the dithiocarbamic acid ester group at the 6‐position of 4‐anilinoquinazoline or 3‐cyano‐4‐anilinoquinoline could improve the inhibitory activity. Different dithiocarbamic acid ester groups significantly affect the activities.