Design, Synthesis and Anti-Proliferative Activities of 2,6-Substituted Thieno[3,2-d] pyrimidine Derivatives Containing ElectrophilicWarheads
文献类型：期刊论文
| 作者 | Zhang, Qiumeng2; Hu, Zonglong1; Shen, Qianqian1; Chen, Yi1 ; Lu, Wei2
|
| 刊名 | MOLECULES
 |
| 出版日期 | 2017-05 |
| 卷号 | 22期号:5 |
| 关键词 | thieno[3,2-d] pyrimidines antitumor activities acrylamide warheads |
| ISSN号 | 1420-3049 |
| DOI | 10.3390/molecules22050788 |
| 文献子类 | Article |
| 英文摘要 | Thieno[3,2-d] pyrimidine as an effective pharmacophore has been extensively studied. However, its 2,6-substituted derivatives are rarely reported. In the present study, eighteen 2,6-substituted thieno[3,2-d] pyrimidine derivatives containing electrophilic warheads were designed based on the first known Fibroblast growth factor receptor-4 (FGFR4) inhibitor Blu9931. Unexpectedly, all of the derivatives exhibited negligible activity against FGFR4. However, most of the target compounds exhibited antiproliferative activities against four human cancer cell lines, including A431, NCI-H1975, Ramos and SNU-16. Compound 12 showed the most potent antiproliferative activities on the above four cell lines with IC50 values of 1.4 mu M, 1.2 mu M, 0.6 mu M, and 2.6 mu M, respectively. Additionally, the antiproliferative activity of 12 against MDA-MB-221 proved that 12 had the selectivity towards certain tumor cell lines. Furthermore, preliminary structure-activity relationship analysis was discussed based on the experimental data. |
| WOS关键词 | TYROSINE KINASE INHIBITOR ; POTENT ANTITUMOR AGENTS ; BIOLOGICAL EVALUATION ; BREAST-CANCER ; FGFR4 ; GROWTH |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000404522900110 |
| 出版者 | MDPI |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272676]  |
| 专题 | 国家新药筛选中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药理学第一研究室 |
| 通讯作者 | Chen, Yi; Lu, Wei |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.East China Normal Univ, Sch Chem & Mol Engn, 3663 North Zhongshan Rd, Shanghai 200062, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Zhang, Qiumeng,Hu, Zonglong,Shen, Qianqian,et al. Design, Synthesis and Anti-Proliferative Activities of 2,6-Substituted Thieno[3,2-d] pyrimidine Derivatives Containing ElectrophilicWarheads[J]. MOLECULES,2017,22(5). |
| APA | Zhang, Qiumeng,Hu, Zonglong,Shen, Qianqian,Chen, Yi,&Lu, Wei.(2017).Design, Synthesis and Anti-Proliferative Activities of 2,6-Substituted Thieno[3,2-d] pyrimidine Derivatives Containing ElectrophilicWarheads.MOLECULES,22(5). |
| MLA | Zhang, Qiumeng,et al."Design, Synthesis and Anti-Proliferative Activities of 2,6-Substituted Thieno[3,2-d] pyrimidine Derivatives Containing ElectrophilicWarheads".MOLECULES 22.5(2017). |
入库方式： OAI收割
来源：上海药物研究所
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