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Design, synthesis, and biological evaluation of thieno[3,2-d]pyrimidine derivatives as potential simplified phosphatidylinositol 3-kinase alpha inhibitors

文献类型：期刊论文

作者Yang, Xiuyan3; Deng, Meng3; Zhang, Xi1; Wang, Yi1; Song, Kun3; Cong, Ruan3; Meng, Linghua1; Zhang, Jian2,3
刊名CHEMICAL BIOLOGY & DRUG DESIGN
出版日期2019-12-01
卷号94期号:6页码:2013-2022
ISSN号1747-0277
关键词PI3K alpha inhibitors proliferation inhibition thieno[3 2-d]pyrimidine derivatives
DOI10.1111/cbdd.13425
通讯作者Meng, Linghua(lhmeng@simm.ac.cn) ; Zhang, Jian(jian.zhang@sjtu.edu.cn)
英文摘要A series of thieno[3,2-d]pyrimidine derivatives as phosphatidylinositol 3-kinase (PI3K) inhibitors was designed using the combination strategy. The synthesis and biological evaluation of the derivatives demonstrated their potent inhibition of PI3K, culminating in the discovery of 7 and 21. Determination of a co-crystal structure of 7 complexed with PI3K alpha provided the structural basis for the high enzymatic activity. Furthermore, cellular investigation of compounds 7 and 21 revealed that they efficiently suppressed cancer cell lines proliferation through inhibition of intracellular PI3K/AKT/mammalian target of rapamycin pathway. The results provided potent simplified inhibitors of PI3K with a promising overall profile and a chemical series for further optimization to progress into vivo experiments.
WOS关键词PHOSPHOINOSITIDE ; PATHWAY ; CANCER ; MUTATIONS ; IDENTIFICATION ; PROLIFERATION ; DISCOVERY ; INSIGHTS ; ISOFORM ; DOCKING
WOS研究方向Biochemistry & Molecular Biology ; Pharmacology & Pharmacy
语种英语
出版者WILEY
WOS记录号WOS:000499105200002
源URL[http://119.78.100.183/handle/2S10ELR8/282038]  
专题中国科学院上海药物研究所
通讯作者Meng, Linghua; Zhang, Jian
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, Shanghai, Peoples R China
2.Shanghai Jiao Tong Univ, Renji Hosp, Basic Clin Res Ctr, Sch Med, Shanghai, Peoples R China
3.Shanghai Jiao Tong Univ, Dept Pathophysiol, Key Lab Cell Differentiat & Apoptosis, Sch Med,Chinese Minist Educ, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Yang, Xiuyan,Deng, Meng,Zhang, Xi,et al. Design, synthesis, and biological evaluation of thieno[3,2-d]pyrimidine derivatives as potential simplified phosphatidylinositol 3-kinase alpha inhibitors[J]. CHEMICAL BIOLOGY & DRUG DESIGN,2019,94(6):2013-2022.
APA Yang, Xiuyan.,Deng, Meng.,Zhang, Xi.,Wang, Yi.,Song, Kun.,...&Zhang, Jian.(2019).Design, synthesis, and biological evaluation of thieno[3,2-d]pyrimidine derivatives as potential simplified phosphatidylinositol 3-kinase alpha inhibitors.CHEMICAL BIOLOGY & DRUG DESIGN,94(6),2013-2022.
MLA Yang, Xiuyan,et al."Design, synthesis, and biological evaluation of thieno[3,2-d]pyrimidine derivatives as potential simplified phosphatidylinositol 3-kinase alpha inhibitors".CHEMICAL BIOLOGY & DRUG DESIGN 94.6(2019):2013-2022.

入库方式： OAI收割

来源：上海药物研究所

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