Design, synthesis and biological evaluation of novel 4-anilinoquinazolines with C-6 urea-linked side chains as inhibitors of the epidermal growth factor receptor
文献类型：期刊论文
| 作者 | Zhang, Xu1,2; Peng, Ting2; Ji, Xun2,3; Li, Jian2; Tong, Linjiang2; Li, Zeng2; Yang, Wei2; Xu, Yungen1; Li, Mengyuan2; Ding, Jian2
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| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY
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| 出版日期 | 2013-12-15 |
| 卷号 | 21期号:24页码:7988-7998 |
| 关键词 | EGFR inhibitor EGFR T790M/L858R Binding mode Irreversible EGFR inhibitor |
| ISSN号 | 0968-0896 |
| DOI | 10.1016/j.bmc.2013.09.049 |
| 文献子类 | Article |
| 英文摘要 | A novel series of anilinoquinazoline compounds with C-6 urea-linked side chains was designed and synthesized as reversible inhibitors of epidermal growth factor receptor (EGFR) based on the structure-activity relationships (SARs) of anilinoquinazoline inhibitors. All compounds demonstrated good inhibition of EGFR wild type (EGFR wt) (IC50 = 0.024-1.715 mu M) and inhibited proliferation of A431cell line (IC50 = 0.116-22.008 mu M). The binding mode of compounds 8a, 8d, 8k and 8o was consistent with the biological results. Moreover, compounds 8k and 8l almost completely blocked the phosphorylation of EGFR in A431 cell line at 0.01 mu M. Interestingly, all of the compounds also demonstrated moderate inhibition of EGFR/T790M/L858R (IC50 = 0.049-5.578 mu M). In addition, compounds 8f and 8h blocked the autophosphorylation of EGFR in NCI-H1975 cells at high concentration (10 mu M), and compound 8f was confirmed to be an irreversible inhibitor through the dilution method. Importantly, the compounds with C-6 urea-linked side chains which did not contain Michael acceptors demonstrated moderate to strong irreversible EGFR inhibition. (C) 2013 Published by Elsevier Ltd. |
| WOS关键词 | TYROSINE KINASE INHIBITORS ; CELL LUNG-CANCER ; ERBB SIGNALING NETWORK ; IRREVERSIBLE INHIBITORS ; EGFR ; OPTIMIZATION ; RESISTANCE ; 4-(PHENYLAMINO)QUINAZOLINE ; MUTATION ; BEARING |
| 资助项目 | National Natural Science Foundation of China[21021063] ; National Natural Science Foundation of China[91229204] ; National Natural Science Foundation of China[81025017] ; National Natural Science Foundation of China[81102307] ; National Natural Science Foundation of China[81173080] ; National S&T Major Projects[2012ZX09103101-072] ; National S&T Major Projects[2012ZX09301001-005] ; Shanghai Committee of Science and Technology[10431902600] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000327766200044 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277335]  |
| 专题 | 药理学第一研究室 药物发现与设计中心 药物化学研究室 |
| 通讯作者 | Xie, Hua |
| 作者单位 | 1.China Pharmaceut Univ, Dept Med Chem, Nanjing 210009, Jiangsu, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; 3.Shenyang Pharmaceut Univ, Sch Pharmaceut Engn, Shenyang 110016, Liaoning, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Xu,Peng, Ting,Ji, Xun,et al. Design, synthesis and biological evaluation of novel 4-anilinoquinazolines with C-6 urea-linked side chains as inhibitors of the epidermal growth factor receptor[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2013,21(24):7988-7998. |
| APA | Zhang, Xu.,Peng, Ting.,Ji, Xun.,Li, Jian.,Tong, Linjiang.,...&Liu, Hong.(2013).Design, synthesis and biological evaluation of novel 4-anilinoquinazolines with C-6 urea-linked side chains as inhibitors of the epidermal growth factor receptor.BIOORGANIC & MEDICINAL CHEMISTRY,21(24),7988-7998. |
| MLA | Zhang, Xu,et al."Design, synthesis and biological evaluation of novel 4-anilinoquinazolines with C-6 urea-linked side chains as inhibitors of the epidermal growth factor receptor".BIOORGANIC & MEDICINAL CHEMISTRY 21.24(2013):7988-7998. |
入库方式： OAI收割
来源：上海药物研究所
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