Design, Synthesis, and Biological Evaluation of Thieno[3,2-d]pyrimidine Derivatives as Potential Simplified Phosphatidylinositol 3-Kinase alpha (PI3Kα) inhibitors
文献类型：期刊论文
| 作者 | Yang, Xiuyan1; Deng, Meng1; Zhang, Xi2; Song, Kun1; Ruan, Cong1; Meng, Linghua2 ; Zhang, Jian1
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| 刊名 | Chemical biology & drug design
 |
| 出版日期 | 2018-10-31 |
| ISSN号 | 1747-0285 |
| DOI | 10.1111/cbdd.13425 |
| 文献子类 | Article |
| 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 PI3Kα 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/mTOR 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. This article is protected by copyright. All rights reserved. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/266322]  |
| 专题 | 药理学第一研究室 |
| 作者单位 | 1.Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai JiaoTong University, School of Medicine, Shanghai, 200025, China; 2.Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, 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 (PI3Kα) inhibitors[J]. Chemical biology & drug design,2018. |
| APA | Yang, Xiuyan.,Deng, Meng.,Zhang, Xi.,Song, Kun.,Ruan, Cong.,...&Zhang, Jian.(2018).Design, Synthesis, and Biological Evaluation of Thieno[3,2-d]pyrimidine Derivatives as Potential Simplified Phosphatidylinositol 3-Kinase alpha (PI3Kα) inhibitors.Chemical biology & drug design. |
| MLA | Yang, Xiuyan,et al."Design, Synthesis, and Biological Evaluation of Thieno[3,2-d]pyrimidine Derivatives as Potential Simplified Phosphatidylinositol 3-Kinase alpha (PI3Kα) inhibitors".Chemical biology & drug design (2018). |
入库方式： OAI收割
来源：上海药物研究所
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