Synthesis and Biological Activities of Novel 2-Aminobenzimidazoles EGFR~(T790M) Inhibitors
文献类型：期刊论文
| 作者 | Duan Jingyi2; Zhang Yinyong1; Qian Anran1; Tong Linjiang1; Xie Hua1 ; Zhou Xianli2
|
| 刊名 | Chinese Journal of Synthetic Chemistry
 |
| 出版日期 | 2018 |
| 卷号 | 26期号:9页码:637-646 |
| 关键词 | 1-fluoro-2-nitroarene trans-4-aminocyclohexanol hydrochloride 2-aminobenzimidazole EGFR~(T790M) inhibitor synthesis biological activity |
| ISSN号 | 1005-1511 |
| 其他题名 | 新型2-氨基苯并咪唑类EGFR~(T790M)抑制剂的合成及其生物活性 |
| 文献子类 | Article |
| 英文摘要 | Fifteen novel 2-aminobenzimidazoles EGFR~(T790M) inhibitors(6a ~ 6o) were synthesized by the reaction of nucleophilic substitution,reduction,cyclization and condensation from 1-fluoro-2-nitroarenes and trans-4-aminocyclohexanol hydrochloride. The structures were characterized by ~1H NMR, ~(13)C NMR and HR-MS(ESI). The in vitro inhibitory activities against tyrosine kinase and in vitro antitumor activities of 6a ~ 6o were tested by ELISA method and SRB method. The results showed that 6l exhibited the best inhibitory activities against EGFR~(T790M)/L858R with IC_(50) of 45. 6 18. 8 nmol·L~(-1), which was superior to lead compound N-(1-((1R,4 R)-4-hydroxycyclohexyl)-7-methyl-1H-benzo[d] imidazol-2-yl)-3-(trifluoromethyl) benzamide (6,IC_(50) 136. 7 9. 1 nmol·L~(-1)) and demonstrated more than 219-fold selectivity over EGFRWT. 6a,6e,6h and 6i exhibited better inhibitory activities against human lung adenocarcinoma cell(NCI-H1975),with IC_(50) of 1. 929 0. 347,2. 168 0. 819, 2. 335 0. 787 and 1. 930 0. 529 mumol·L~(-1),which were superior to lead compound 6(2. 653 1. 395 mumol·L~(-1)). |
| 资助项目 | 中科院战略性先导科技专项子课题[00000000] |
| WOS研究方向 | Chemistry (provided by Clarivate Analytics) |
| 语种 | 中文 |
| CSCD记录号 | CSCD:6335140 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/269155]  |
| 专题 | 药物化学研究室 药理学第一研究室 |
| 作者单位 | 1.Shanghai Institute of Materia Medica,Chinese Academy of Sciences, Shanghai 201203, China. 2.School of Life Science and Engineering,Southwest Jiaotong University, Chengdu, Sichuan 610031, China.; |
| 推荐引用方式 GB/T 7714 | Duan Jingyi,Zhang Yinyong,Qian Anran,et al. Synthesis and Biological Activities of Novel 2-Aminobenzimidazoles EGFR~(T790M) Inhibitors[J]. Chinese Journal of Synthetic Chemistry,2018,26(9):637-646. |
| APA | Duan Jingyi,Zhang Yinyong,Qian Anran,Tong Linjiang,Xie Hua,&Zhou Xianli.(2018).Synthesis and Biological Activities of Novel 2-Aminobenzimidazoles EGFR~(T790M) Inhibitors.Chinese Journal of Synthetic Chemistry,26(9),637-646. |
| MLA | Duan Jingyi,et al."Synthesis and Biological Activities of Novel 2-Aminobenzimidazoles EGFR~(T790M) Inhibitors".Chinese Journal of Synthetic Chemistry 26.9(2018):637-646. |
入库方式： OAI收割
来源：上海药物研究所
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