title: 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.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, P R China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Ridong
authors.initials: R
authors.lastname: Li
authors.forename: Kang
authors.initials: K
authors.lastname: Qiao
authors.forename: Zemei
authors.initials: Z
authors.lastname: Ge
authors.forename: Liangren
authors.initials: L
authors.lastname: Zhang
authors.forename: Tieming
authors.initials: T
authors.lastname: Cheng
authors.forename: Runtao
authors.initials: R
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D000077341:Lapatinib; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004952:Esters; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D011804:Quinolines; D000077341:Lapatinib; D066246:ErbB Receptors