56128-66-6Relevant articles and documents
Design, synthesis and biological evaluation of 2,3-dihydro-[1,4]dioxino[2,3-f]quinazoline derivatives as EGFR inhibitors
Qin, Xuemei,Yang, Leifu,Liu, Peng,Yang, Lifang,Chen, Linmeng,Hu, Liming,Jiang, Mingguo
, (2021)
Epidermal growth factor receptor (EGFR) is the most attractive target for drug research in non-small cell lung cancer (NSCLC). The first-generation EGFR tyrosine kinase inhibitors (TKIs) Gefetinib and Elotinib showed good clinical efficacy on lung adenocarcinoma tumors, but almost all patients developed resistance to these inhibitors over time. Quinazoline and quinoline derivatives are common targeted inhibitors of EGFR kinase, and their structural optimization is an important direction for the development of effective targeted anticancer drugs. Based on these facts, a series of heterocyclic 2,3-dihydro-[1,4]dioxino[2,3-f]quinazoline derivatives have been designed and synthesized and their structures were confirmed by spectral analyses. The cytotoxic activity of the newly synthesized compounds was evaluated against the human kidney epithelial T293 cell line, normal lung cell lines WI-38, non-small cell lung cancer A549 and NCI-H157 cell lines using MTT. The tested compounds showed an evident anticancer activity against the tested cell lines, especially compound 13c, which was the most potent anticancer agent with half maximal inhibitory concentrations (IC50) between 8.82 and 10.24 μM. Docking study showed that compound 13b could be nicely bound to the ATP binding pocket of EGFR. In addition, the inhibitory activity of the target compounds against epidermal growth factor receptor tyrosine kinase (EGFR-TK) was evaluated. Results indicated the ability of the target compounds to inhibit EGFR-TK with half maximal inhibitory concentrations (IC50) in the range of 10.29 nM to 652.3 nM. In view of the reported compound activity, the structure deserves further optimization as cancer treatment agents.
Discovery of new [1,4]dioxino[2,3-f]quinazoline-based inhibitors of EGFR including the T790M/L858R mutant
Qin, Xuemei,Li, Zhipeng,Yang, Leifu,Liu, Peng,Hu, Liming,Zeng, Chengchu,Pan, Zhiyong
, p. 2871 - 2881 (2016)
A novel series of 2,3-dihydro-[1,4]dioxino[2,3-f]quinazoline derivatives were designed, synthesized and evaluated as reversible and noncovalent epidermal growth factor receptor (EGFR) inhibitors. Most of the compounds exhibited good potency against EGFRwt and some showed moderate to excellent potency against EGFRT790M/L858R mutant. The half-maximal inhibitory concentration (IC50) values of twenty-one compounds against EGFRwt were less than 50 nM, and those of six compounds were less than 10 nM. The IC50 values of eleven compounds against EGFRT790M/L858R were less than 100 nM. Among these, compound b1 displayed the most potent inhibitory activity against EGFRwt (IC50 = 2.0 nM) and EGFRT790M/L858R (IC50 = 6.9 nM). Compounds with excellent inhibitory activities against EGFRwt and EGFRT790M/L858R kinase inhibitory activities showed good antiproliferative activities against H358 and A549 cells. Docking study was performed to position compound b1 into the EGFR active pocket to determine the probable binding conformation.
QUINAZOLINE HETEROCYCLIC COMPOUND AS EGFR KINASE INHIBITOR AND PREPARATION AND APPLICATION THEREOF
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Paragraph 0064; 0065, (2018/01/19)
The present invention relates to an N-substituted-phenyl-5-substituted-alkoxy-2,3-dihydro-[1,4]dioxane[2,3-f]quinazolin-10-amine (I) or 4-substituted-arylamino-6-substituted-alkyl-6H-[1,4]oxazino[3,2-g]quinazoline-7(8H)-one (II) type compounds, a preparation method thereof and an application thereof as an inhibitor for epidermal growth factor receptor (EGFR) (comprising some mutant forms of EGFR) to treat cancer. These compounds and salts thereof can be used to treat or prevent various cancer diseases.
