Optimization and Synthesis of Pyridazinone Derivatives as Novel Inhibitors of Hepatitis B Virus by Inducing Genome-free Capsid Formation
文献类型：期刊论文
| 作者 | Lu, Dong1,2; Liu, Feifei1,3; Xing, Weiqiang2; Tong, Xiankun3 ; Wang, Lang2; Wang, Yajuan1,3; Zeng, Limin2; Feng, Chunlan3; Yang, Li3; Zuo, Jianping3
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| 刊名 | ACS INFECTIOUS DISEASES
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| 出版日期 | 2017-03 |
| 卷号 | 3期号:3页码:199-205 |
| ISSN号 | 2373-8227 |
| 关键词 | pyridazinone HBV DNA-free capsids drug-like optimization SAR study lead candidate |
| DOI | 10.1021/acsinfecdis.6b00159 |
| 文献子类 | Article |
| 英文摘要 | The capsid of hepatitis B virus (HBV) plays a vital role in virus DNA replication. Targeting nucleocapsid function has been demonstrated as an effective approach for anti-HBV drug development. A high-throughput screening and mechanism study revealed the hit compound 4a as an HBV assembly effector (AEf), which could inhibit HBV replication by inducing the formation of HBV DNA-free capsids. The subsequent SAR study and drug-like optimization resulted in the discovery of the lead candidate 4r, with potent antiviral activity (IC50 = 0.087 +/- 0.002 mu M), low cytotoxicity (CC50 = 90.6 +/- 2.06 mu M), sensitivity to nucleoside analogue -resistant HBV mutants, and synergistic effect with nucleoside analogues in HepG2.2.15 cells. |
| WOS关键词 | SMALL-MOLECULE INHIBITORS ; IN-VITRO ; PHENYLPROPENAMIDE DERIVATIVES ; HEPATOCELLULAR-CARCINOMA ; ANTIVIRAL TREATMENT ; LAMIVUDINE THERAPY ; HBV REPLICATION ; C-VIRUS ; INFECTION ; DESIGN |
| 资助项目 | National Science Fund[81225022] ; National Science Fund[81322049] ; National Science Fund[31570166] ; National Program on Key Basic Research Project (973 Program)[2013CB911104] ; Institutes for Drug Discovery and Development, Chinese Academy of Sciences[CA-SIMM0120162013] |
| WOS研究方向 | Pharmacology & Pharmacy ; Infectious Diseases |
| 语种 | 英语 |
| 出版者 | AMER CHEMICAL SOC |
| WOS记录号 | WOS:000396384800003 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272750]  |
| 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 | Yang, Li; Zuo, Jianping; Hu, Youhong |
| 作者单位 | 1.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 ZuChongZhi Rd, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Lab Immunopharmacol, 555 ZuChongZhi Rd, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Lu, Dong,Liu, Feifei,Xing, Weiqiang,et al. Optimization and Synthesis of Pyridazinone Derivatives as Novel Inhibitors of Hepatitis B Virus by Inducing Genome-free Capsid Formation[J]. ACS INFECTIOUS DISEASES,2017,3(3):199-205. |
| APA | Lu, Dong.,Liu, Feifei.,Xing, Weiqiang.,Tong, Xiankun.,Wang, Lang.,...&Hu, Youhong.(2017).Optimization and Synthesis of Pyridazinone Derivatives as Novel Inhibitors of Hepatitis B Virus by Inducing Genome-free Capsid Formation.ACS INFECTIOUS DISEASES,3(3),199-205. |
| MLA | Lu, Dong,et al."Optimization and Synthesis of Pyridazinone Derivatives as Novel Inhibitors of Hepatitis B Virus by Inducing Genome-free Capsid Formation".ACS INFECTIOUS DISEASES 3.3(2017):199-205. |
入库方式： OAI收割
来源：上海药物研究所
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