Discovery and optimization of phthalazinone derivatives as a new class of potent dengue virus inhibitors
文献类型：期刊论文
| 作者 | Lu, Dong1,2; Liu, Jianan1,2; Zhang, Yunzhe3; Liu, Feifei1,2; Zeng, Limin1; Peng, Runze1,2; Yang, Li1; Ying, Huazhou3; Tang, Wei1 ; Chen, Wuhong1
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| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2018-02-10 |
| 卷号 | 145页码:328-337 |
| 关键词 | Phthalazinone Dengue virus Inhibitor Optimization SAR |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2018.01.008 |
| 文献子类 | Article |
| 英文摘要 | Using a dengue replicon cell line-based screening, we identified 3-(dimethylamino)propyl(3-((4-(4-fluorophenyl)-1-oxophthalazin-2(1H)-yl)methypphenyl)carbamate (10a) as a potent DENV-2 inhibitor, with an IC50 value of 0.64 mu M. A series of novel phthalazinone derivatives based on hit 10a were synthesized and evaluated for their in vitro anti-DENV activity and cytotoxicity. The subsequent SAR study and optimization led to the discovery of the most promising compound 141, which displayed potent anti-DENV-2 activity, with low IC50 value against DENV-2 RNA replication of 0.13 mu M and high selectivity (SI = 89.2) with acceptable pharmacokinetics profiles. (C) 2018 Elsevier Masson SAS. All rights reserved. |
| WOS关键词 | INFECTION ; PERSPECTIVE ; PROSPECTS ; PROGRESS |
| 资助项目 | National Key Research and Development Program of China[2016YFC1200400] ; Defense Technology Innovation Fund, Chinese Academy of Sciences[CXJJ-17-Q147] ; National Natural Science Foundation of China[00000000] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000425198200026 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279906]  |
| 专题 | 药理学第一研究室 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 药物发现与设计中心 药物化学研究室 |
| 通讯作者 | Tong, Xiankun; Liu, Tao; Hu, Youhong |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China; 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 3.Zhejiang Univ, Coll Pharmaceut Sci, Zhejiang Prov Key Lab Anticanc Drug Res, Hangzhou 310058, Zhejiang, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Lu, Dong,Liu, Jianan,Zhang, Yunzhe,et al. Discovery and optimization of phthalazinone derivatives as a new class of potent dengue virus inhibitors[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2018,145:328-337. |
| APA | Lu, Dong.,Liu, Jianan.,Zhang, Yunzhe.,Liu, Feifei.,Zeng, Limin.,...&Hu, Youhong.(2018).Discovery and optimization of phthalazinone derivatives as a new class of potent dengue virus inhibitors.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,145,328-337. |
| MLA | Lu, Dong,et al."Discovery and optimization of phthalazinone derivatives as a new class of potent dengue virus inhibitors".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 145(2018):328-337. |
入库方式： OAI收割
来源：上海药物研究所
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