Novel thiophene derivatives as PTP1B inhibitors with selectivity and cellular activity
文献类型：期刊论文
| 作者 | Ye, Deju2; Zhang, Yu2; Wang, Fei2; Zheng, Mingfang2; Zhang, Xu1,2; Luo, Xiaomin2 ; Shen, Xu2; Jiang, Hualiang2,3; Liu, Hong1,2
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| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY
 |
| 出版日期 | 2010-03-01 |
| 卷号 | 18期号:5页码:1773-1782 |
| 关键词 | Protein tyrosine phosphatase 1B (PTP1B) Inhibitors Thiophene Structure-activity relationships (SAR) |
| ISSN号 | 0968-0896 |
| DOI | 10.1016/j.bmc.2010.01.055 |
| 文献子类 | Article |
| 英文摘要 | A series of novel thiophene derivatives was designed, synthesized and their activities as competitive inhibitors of protein tyrosine phosphatase (PTPs) 1B (PTP1B) inhibitors were evaluated. All the compounds showed inhibitory potencies, and 10 of these exhibited moderate inhibitory activities with IC50 values less than 10 mu M. The activity of the most potent compound P28 (IC50 = 2.1 mu M) was 15 times higher than that of the hit compound P01. Further, four representative compounds (P19, P22, P28, and P31) demonstrated remarkably high selectivities against other PTPs (e. g., PTP alpha, LAR, CD45, and TCPTP); P19 exhibited greater than sixfold selectivity over highly homologous TCPTP. More importantly, these compounds are permeable to cell membranes. The treatment of CHO-K1 cells with P28 (10 mu M) resulted in increased phosphorylation of AKT, which suggested extensive cellular activity of this compound. The novel chemical entities reported in this study could be used for overcoming the poor selectivity and low cellular activity of PTP1B inhibitors and might represent a starting point for development of therapeutic PTP inhibitors. (C) 2010 Elsevier Ltd. All rights reserved. |
| WOS关键词 | PROTEIN-TYROSINE-PHOSPHATASE ; 1B INHIBITORS ; INSULIN SENSITIVITY ; MICE ; DISCOVERY ; TRANSPORT ; GLUCOSE ; OBESITY |
| 资助项目 | National Natural Science Foundation of China[20721003] ; National Natural Science Foundation of China[20872153] ; International Collaboration Projects[20720 102040] ; 863 Hi-Tech Program of China[2006AA 020402] ; 863 Hi-Tech Program of China[2006AA020602] ; National S&T Major Projects[2009ZX09501-001] ; National S&T Major Projects[2009ZX09501-010] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000274957100003 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278958]  |
| 专题 | 药物化学研究室 药物发现与设计中心 |
| 通讯作者 | Liu, Hong |
| 作者单位 | 1.China Pharmaceut Univ, Dept Med Chem, Nanjing 210009, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr,State Key Lab Drug Re, Shanghai 201203, Peoples R China; 3.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ye, Deju,Zhang, Yu,Wang, Fei,et al. Novel thiophene derivatives as PTP1B inhibitors with selectivity and cellular activity[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2010,18(5):1773-1782. |
| APA | Ye, Deju.,Zhang, Yu.,Wang, Fei.,Zheng, Mingfang.,Zhang, Xu.,...&Liu, Hong.(2010).Novel thiophene derivatives as PTP1B inhibitors with selectivity and cellular activity.BIOORGANIC & MEDICINAL CHEMISTRY,18(5),1773-1782. |
| MLA | Ye, Deju,et al."Novel thiophene derivatives as PTP1B inhibitors with selectivity and cellular activity".BIOORGANIC & MEDICINAL CHEMISTRY 18.5(2010):1773-1782. |
入库方式： OAI收割
来源：上海药物研究所
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