Design, synthesis and evaluation of novel oxazaphosphorine prodrugs of 9-(2-phosphonomethoxyethyl)adenine (PMEA, adefovir) as potent HBV inhibitors
文献类型：期刊论文
| 作者 | Lu, Peng1; Liu, Jiangxia2; Wang, Yuya1; Chen, Xiaoyan1 ; Yang, Yushe1; Ji, Ruyun1
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| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
 |
| 出版日期 | 2009-12-15 |
| 卷号 | 19期号:24页码:6918-6921 |
| 关键词 | Oxazaphosphorine Prodrug Hepatitis B virus |
| ISSN号 | 0960-894X |
| DOI | 10.1016/j.bmcl.2009.10.072 |
| 文献子类 | Article |
| 英文摘要 | A series of novel oxazaphosphorine prodrugs of 9-(2-phosphonomethoxyethyl)adenine (PMEA, adefovir) were synthesized and their anti-hepatitis B virus (HBV) activity was evaluated in HepG2 2.2.15 cells, with adefovir dipivoxil as a reference drug. In the cell assays, compounds 7b and 7d exhibited anti-HBV activity comparable to that of adefovir dipivoxil, while compound 7c, with an IC50 value of 0.12 mu M, was found to be three times more potent than the reference compound. In vitro stability studies showed that (S-P,S)-7c, the diastereomer of compound 7c, was stable in human blood plasma but underwent rapid metabolism to release the parent drug PMEA in liver microsomes. The possible metabolic pathway of (S-P,S)-7c in human liver microsomes was described. These findings suggest that compound (S-P,S)-7c is a promising anti-HBV drug candidate for further development. (C) 2009 Elsevier Ltd. All rights reserved. |
| WOS关键词 | CHRONIC HEPATITIS-B ; INTRACELLULAR DELIVERY ; HYDROXAMIC ACIDS ; VIRUS-INFECTION ; DERIVATIVES ; CELLS ; 9-(2-PHOSPHONYLMETHOXYETHYL)ADENINE ; 5'-MONOPHOSPHATE ; PHOSPHONATES ; NUCLEOTIDES |
| WOS研究方向 | Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000271724200020 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279063]  |
| 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 | Yang, Yushe |
| 作者单位 | 1.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai Inst Biol Sci, Shanghai 201203, Peoples R China; 2.Fudan Univ, Key Lab Med Mol Viol, Inst Med Microbiol, Shanghai Med Coll, Shanghai 200032, Peoples R China |
| 推荐引用方式 GB/T 7714 | Lu, Peng,Liu, Jiangxia,Wang, Yuya,et al. Design, synthesis and evaluation of novel oxazaphosphorine prodrugs of 9-(2-phosphonomethoxyethyl)adenine (PMEA, adefovir) as potent HBV inhibitors[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2009,19(24):6918-6921. |
| APA | Lu, Peng,Liu, Jiangxia,Wang, Yuya,Chen, Xiaoyan,Yang, Yushe,&Ji, Ruyun.(2009).Design, synthesis and evaluation of novel oxazaphosphorine prodrugs of 9-(2-phosphonomethoxyethyl)adenine (PMEA, adefovir) as potent HBV inhibitors.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,19(24),6918-6921. |
| MLA | Lu, Peng,et al."Design, synthesis and evaluation of novel oxazaphosphorine prodrugs of 9-(2-phosphonomethoxyethyl)adenine (PMEA, adefovir) as potent HBV inhibitors".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 19.24(2009):6918-6921. |
入库方式： OAI收割
来源：上海药物研究所
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