Discovery of Phthalazinone Derivatives as Novel Hepatitis B Virus Capsid Inhibitors
文献类型：期刊论文
| 作者 | Chen, Wuhong4; Liu, Feifei1,2; Zhao, Qiliang1,4; Ma, Xinna2,3; Lu, Dong4; Li, Heng1,2; Zeng, Yanping1,4; Tong, Xiankun2 ; Zeng, Limin4; Liu, Jia4
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| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2020-08-13 |
| 卷号 | 63期号:15页码:8134-8145 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.0c00346 |
| 通讯作者 | Yang, Li(yangli@simm.ac.cn) ; Zuo, Jianping(jpzuo@simm.ac.cn) ; Hu, Youhong(yhhu@simm.ac.cn) |
| 英文摘要 | HBV capsid assembly has been viewed as an attractive target for new antiviral therapies against HBV. On the basis of a lead compound 4r, we further investigated this target to identify novel active compounds with appropriate anti-HBV potencies and improved pharmacokinetic (PK) properties. Structure-activity relationship studies based on metabolic pathways of 4r led to the identification of a phthalazinone derivative 19f with appropriate anti-HBV potencies (IC50 = 0.014 +/- 0.004 mu M in vitro), which demonstrated high oral bioavailability and liver exposure. In the AAV-HBV/mouse model, administration of 191 resulted in a 2.67 log reduction of the HBV DNA viral load during a 4-week treatment with 150 mg/kg dosing twice daily. |
| WOS关键词 | REPLICATION ; DESIGN ; ANALOGS |
| 资助项目 | National Natural Science Foundation of China[81872725] ; Science and Technology Commission of Shanghai Municipality[18431907100] ; National Science Foundation of Shanghai[17ZR1436400] ; National Science and Technology Major Project[2018ZX09711002-014-004] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | AMER CHEMICAL SOC |
| WOS记录号 | WOS:000562941200013 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/292430]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Yang, Li; Zuo, Jianping; Hu, Youhong |
| 作者单位 | 1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Lab Immunopharmacol, Shanghai 201203, Peoples R China 3.Shanghai Univ Tradit Chinese Med, Lab Immunol & Virol, Shanghai 201203, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 5.Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Wuhong,Liu, Feifei,Zhao, Qiliang,et al. Discovery of Phthalazinone Derivatives as Novel Hepatitis B Virus Capsid Inhibitors[J]. JOURNAL OF MEDICINAL CHEMISTRY,2020,63(15):8134-8145. |
| APA | Chen, Wuhong.,Liu, Feifei.,Zhao, Qiliang.,Ma, Xinna.,Lu, Dong.,...&Hu, Youhong.(2020).Discovery of Phthalazinone Derivatives as Novel Hepatitis B Virus Capsid Inhibitors.JOURNAL OF MEDICINAL CHEMISTRY,63(15),8134-8145. |
| MLA | Chen, Wuhong,et al."Discovery of Phthalazinone Derivatives as Novel Hepatitis B Virus Capsid Inhibitors".JOURNAL OF MEDICINAL CHEMISTRY 63.15(2020):8134-8145. |
入库方式： OAI收割
来源：上海药物研究所
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