title: Discovery of novel 4-anilinoquinazoline derivatives as potent inhibitors of epidermal growth factor receptor with antitumor activity.
abstract: Two new series of new compounds containing a 6-amino-substituted group or 6-acrylamide-substituted group linked to a 4-anilinoquinazoline nucleus have been discovered as potential EGFR inhibitors. These compounds proved efficient effects on antiproliferative activity and EGFR-TK inhibitory activity. Especially, N(6)-((5-bromothiophen-2-yl)methyl)-N(4)-(3-chlorophenyl)quinazoline-4,6-diamine (5e), showed the most potent inhibitory activity (IC50=3.11μM for Hep G2, IC50=0.82μM for A549). The EGFR molecular docking model suggested that the new compound is nicely bound to the region of EGFR, and cell morphology by Hoechst stain experiment suggested that these compounds efficiently induced apoptosis of A549 cells.
authors: College of Pharmaceutical Science, Soochow University, Suzhou 215123, PR China.
authors: Yun-Yun
authors: YY
authors: Xu
authors: Si-Ning
authors: SN
authors: Li
authors: Gao-Jian
authors: GJ
authors: Yu
authors: Qing-Hua
authors: QH
authors: Hu
authors: Huan-Qiu
authors: HQ
authors: Li
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D055808:Drug Discovery; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: C527769:6-hydroxypropynyl-4-anilinoquinazoline; D000814:Aniline Compounds; D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors
keywords: 4-Anilinoquinazoline; Antitumor; EGFR–TK inhibitors; Molecular docking