Design, synthesis, and biological evaluation of novel 2-ethyl-5-phenylthiazole-4-carboxamide derivatives as protein tyrosine phosphatase 1B inhibitors with improved cellular efficacy
文献类型：期刊论文
| 作者 | Chen, Yue-Ting ; Tang, Chun-Lan; Ma, Wei-Ping; Gao, Li-Xin; Wei, Yi; Zhang, Wei; Li, Jing-Ya; Li, Jia; Nan, Fa-Jun
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| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2013-11 |
| 卷号 | 69页码:399-412 |
| 关键词 | Protein tyrosine phosphatase 1B Type 2 diabetes 2-Ethyl-5-phenylthiazole-4-carboxamide (PTA) SAR |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2013.09.017 |
| 文献子类 | Article |
| 英文摘要 | Protein tyrosine phosphatase 1B (PTP1B) is implicated as a key negative regulator of the insulin and leptin signal-transduction pathways. PTP1B inhibitors have emerged as attractive and potent pharmaceutical agents for the treatment of type 2 diabetes and obesity. We identified a series of 2-ethy1-5-phenylthiazole-4-carboxamide (PTA) derivatives, inspired from the ACT scaffold of Scleritodermin A, as a novel class of PTP1B inhibitors. Structure-activity relationship (SAR) analysis and docking studies revealed the molecular basis of PTP1B inhibition by these compounds. PTA derivative 18g was capable of inhibiting intracellular PTP1B and subsequently activating the insulin signaling pathway. Treatment of cells with 18g markedly increased the phosphorylation levels of IRP and Akt as well as the rate of glucose uptake. (C) 2013 Elsevier Masson SAS. All rights reserved. |
| WOS关键词 | INSULIN SENSITIVITY ; SCLERITODERMIN-A ; DRUG TARGETS ; BINDING-SITE ; BODY-WEIGHT ; IN-VIVO ; PTP1B ; OBESITY ; RESISTANCE ; GLUCOSE |
| 资助项目 | National Natural Science Foundation of China[81125023] ; National Natural Science Foundation of China[30725049] ; National Natural Science Foundation of China[30901850] ; National Basic Research Program of China[2012CB524906] ; National Science and Technology Major Projects for Major New Drugs Innovation and Development[2013ZX09507002] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000330603900039 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277385]  |
| 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 |
| 通讯作者 | Nan, Fa-Jun |
| 作者单位 | Chinese Acad Sci, Chinese Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Yue-Ting,Tang, Chun-Lan,Ma, Wei-Ping,et al. Design, synthesis, and biological evaluation of novel 2-ethyl-5-phenylthiazole-4-carboxamide derivatives as protein tyrosine phosphatase 1B inhibitors with improved cellular efficacy[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2013,69:399-412. |
| APA | Chen, Yue-Ting.,Tang, Chun-Lan.,Ma, Wei-Ping.,Gao, Li-Xin.,Wei, Yi.,...&Nan, Fa-Jun.(2013).Design, synthesis, and biological evaluation of novel 2-ethyl-5-phenylthiazole-4-carboxamide derivatives as protein tyrosine phosphatase 1B inhibitors with improved cellular efficacy.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,69,399-412. |
| MLA | Chen, Yue-Ting,et al."Design, synthesis, and biological evaluation of novel 2-ethyl-5-phenylthiazole-4-carboxamide derivatives as protein tyrosine phosphatase 1B inhibitors with improved cellular efficacy".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 69(2013):399-412. |
入库方式： OAI收割
来源：上海药物研究所
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