Design, Synthesis and Anti-Proliferative Activities of 2,6-Substituted Thieno[3,2-d] pyrimidine Derivatives Containing ElectrophilicWarheads

doi:10.3390/molecules22050788

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	Design, Synthesis and Anti-Proliferative Activities of 2,6-Substituted Thieno[3,2-d] pyrimidine Derivatives Containing ElectrophilicWarheads
	Zhang, Qiumeng 2; Hu, Zonglong 1; Shen, Qianqian 1; Chen, Yi1 ; Lu, Wei 2
刊名	MOLECULES
	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
出版者	MDPI
WOS记录号	WOS:000404522900110
内容类型	期刊论文
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).