title: Synthesis and in vitro biological evaluation of novel quinazoline derivatives.
abstract: A series of novel 4-arylamino-6-(5-substituted furan-2-yl)quinazoline derivatives were designed, synthesized and evaluated on biological activities in vitro. Compound 2a, 3a and 3c exhibited highly anti-proliferation activities on all tested tumor cell lines including SW480, A549, A431 and NCI-H1975 cells. Especially, compound 2a not only exhibited strong anti-proliferation activities against the tumor cell lines which expressed wild type or mutant EGFRL858R/T790M, but also showed the most potent inhibitory activity toward wild type EGFR (IC50=5.06nM). The result of docking with EGFR suggested the binding mode of 2a was similar to that of lapatinib. While Western-blot analyses showed 2a obviously inhibited the activation of EGFR, Akt and Erk1/2 in lung cancer cells at indicated concentration. It is believed that this work would be very useful for developing a new series of TKIs targeting EGFR.
authors.affiliation: Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China; School of Chemistry & Chemical Engineering, Shaanxi Normal University, Xi'an 710062, PR China.
authors.forename: Yaling
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China; School of Chemistry & Chemical Engineering, Shaanxi Normal University, Xi'an 710062, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China; School of Chemistry & Chemical Engineering, Shaanxi Normal University, Xi'an 710062, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China; School of Chemistry & Chemical Engineering, Shaanxi Normal University, Xi'an 710062, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China; School of Chemistry & Chemical Engineering, Shaanxi Normal University, Xi'an 710062, PR China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China; School of Chemistry & Chemical Engineering, Shaanxi Normal University, Xi'an 710062, PR China. Electronic address: baolinli@snnu.edu.cn.
authors.forename: Baolin
authors.initials: B
authors.lastname: Li
authors.affiliation: Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China; School of Chemistry & Chemical Engineering, Shaanxi Normal University, Xi'an 710062, PR China. Electronic address: wwlzz@snnu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D000077156:Gefitinib; D006801:Humans; D000077341:Lapatinib; D062105:Molecular Docking Simulation; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D011799:Quinazolines / Q000138:chemical synthesis / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: C000621532:4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(5-hydroxymethylfuran-2-yl)quinazoline; D000814:Aniline Compounds; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000077341:Lapatinib; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: 4-Arylamino-6-(5-substituted furan-2-yl)quinazoline; Anti-proliferation; EGFR; Tyrosine kinase inhibitors