Design and discovery of new pyrimidine coupled nitrogen aromatic rings as chelating groups of JMJD3 inhibitors
文献类型：期刊论文
| 作者 | Hu, Jianping2; Wang, Xin2 ; Chen, Lin2; Huang, Min1; Tang, Wei1; Zuo, Jianping1; Liu, Yu-Chih3; Shi, Zhe3; Liu, Rongfeng3; Shen, Jingkang2
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| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
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| 出版日期 | 2016-02-01 |
| 卷号 | 26期号:3页码:721-725 |
| 关键词 | Epigenetics Histone demethylase JMJD3 inhibitors GSK-J1 Chelating group |
| ISSN号 | 0960-894X |
| DOI | 10.1016/j.bmcl.2016.01.006 |
| 文献子类 | Article |
| 英文摘要 | The histone methylation on lysine residues is one of the most studied post-translational modifications, and its aberrant states have been associated with many human diseases. In 2012, Kruidenier et al. reported GSK-J1 as a selective Jumonji H3K27 demethylase (JMJD3 and UTX) inhibitor. However, there is limited information on the structure-activity relationship of this series of compounds. Moreover, there are few scaffolds reported as chelating groups for Fe(II) ion in Jumonji demethylase inhibitors development. To further elaborate the structure-activity relationship of selective JMJD3 inhibitors and to explore the novel chelating groups for Fe(II) ion, we initialized a medicinal chemistry modification based on the GSK-J1 structure. Finally, we found that several compounds bearing different chelating groups showed similar activities with respect to GSK-J1 and excellent metabolic stability in liver microsomes. The ethyl ester prodrugs of these inhibitors also showed a better activity than GSK-J4 for inhibition of TNF-alpha production in LPS-stimulated murine macrophage cell line Raw 264.7 cells. Taking together, the current study not only discovered alternative potent JMJD3 inhibitors, but also can benefit other researchers to design new series of Jumonji demethylase inhibitors based on the identified chelating groups. (C) 2016 Elsevier Ltd. All rights reserved. |
| WOS关键词 | DEMETHYLASE INHIBITORS ; HUMAN-DISEASE ; HISTONE ; TARGETS ; THERAPY |
| 资助项目 | National Natural Science Foundation of China[81273368] ; National Natural Science Foundation of China[81330076] ; National Natural Science Foundation of China[81473094] ; National Science & Technology Major Project 'Key New Drug Creation and Manufacturing Program' of China[2014ZX09507-002] ; National Science & Technology Major Project 'Key New Drug Creation and Manufacturing Program' of China[2013ZX09507001] |
| WOS研究方向 | Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000368797600003 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276167]  |
| 专题 | 药物化学研究室 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 | Shen, Jingkang; Xiong, Bing |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Pharmacol, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; 3.Shanghai ChemPartner Co LTD, Pudong New Area, Bldg 5,998 Halei Rd,Zhangjiang Hitech Pk, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Hu, Jianping,Wang, Xin,Chen, Lin,et al. Design and discovery of new pyrimidine coupled nitrogen aromatic rings as chelating groups of JMJD3 inhibitors[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2016,26(3):721-725. |
| APA | Hu, Jianping.,Wang, Xin.,Chen, Lin.,Huang, Min.,Tang, Wei.,...&Xiong, Bing.(2016).Design and discovery of new pyrimidine coupled nitrogen aromatic rings as chelating groups of JMJD3 inhibitors.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,26(3),721-725. |
| MLA | Hu, Jianping,et al."Design and discovery of new pyrimidine coupled nitrogen aromatic rings as chelating groups of JMJD3 inhibitors".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 26.3(2016):721-725. |
入库方式： OAI收割
来源：上海药物研究所
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