Discovery of pyrimidine nucleoside dual prodrugs and pyrazine nucleosides as novel anti-HCV agents
文献类型：期刊论文
| 作者 | Guo, Shuang1,2; Xu, Mingshuo1,2; Guo, Qi1,2; Zhu, Fuqiang3; Jiang, Xiangrui1 ; Xie, Yuanchao1; Shen, Jingshan1,2
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| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY
 |
| 出版日期 | 2019-03-01 |
| 卷号 | 27期号:5页码:748-759 |
| 关键词 | Nucleoside Double prodrug Phosphoramidate Anti-HCV Pyrazine |
| ISSN号 | 0968-0896 |
| DOI | 10.1016/j.bmc.2019.01.007 |
| 通讯作者 | Xie, Yuanchao(xieyuanchao@simm.ac.cn) |
| 英文摘要 | To explore the application potential of dual prodrug strategies in the development of anti-HCV agents, a variety of sofosbuvir derivatives with modifications at the C4 or N3 position of the uracil moiety were designed and synthesized. Some compounds exhibited potent anti-HCV activities, such as 4e and 8a-8c with similar EC50 values (0.20-0.22 mu M) comparative to that of sofosbuvir (EC50= 0.18 mu M) in a genotype 1b based replicon Huh7 cell line. Moreover, 8b displayed a good human plasma stability profile, and was easily metabolized in human liver microsomes expectantly. On the other hand, aiming to discover novel anti-HCV nucleosides, pyrazin-2(1H)-one nucleosides and their phosphoramidate prodrugs were investigated. Several active compounds were discovered, such as 25e (EC50= 7.3 mu M) and S-29b (EC50= 19.5 mu M). This kind of nucleosides were interesting and would open a new avenue for the development of antiviral agents. |
| WOS关键词 | BIOLOGICAL EVALUATION ; INHIBITORS ; NUCLEOTIDE ; ISOFLAVONES ; ANALOGS ; T-705 |
| 资助项目 | National Science Foundation for Young Scientists of China[21502209] ; China Postdoctoral Science Foundation[2016T90395] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000458293000008 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/290440]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Xie, Yuanchao |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 3.Topharman Shanghai Co Ltd, 388 Jialilue Rd,Zhangjiang Hitech Pk, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Guo, Shuang,Xu, Mingshuo,Guo, Qi,et al. Discovery of pyrimidine nucleoside dual prodrugs and pyrazine nucleosides as novel anti-HCV agents[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2019,27(5):748-759. |
| APA | Guo, Shuang.,Xu, Mingshuo.,Guo, Qi.,Zhu, Fuqiang.,Jiang, Xiangrui.,...&Shen, Jingshan.(2019).Discovery of pyrimidine nucleoside dual prodrugs and pyrazine nucleosides as novel anti-HCV agents.BIOORGANIC & MEDICINAL CHEMISTRY,27(5),748-759. |
| MLA | Guo, Shuang,et al."Discovery of pyrimidine nucleoside dual prodrugs and pyrazine nucleosides as novel anti-HCV agents".BIOORGANIC & MEDICINAL CHEMISTRY 27.5(2019):748-759. |
入库方式： OAI收割
来源：上海药物研究所
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