Antiviral activity of novel 2′-fluoro-6′-methylene-carbocyclic adenosine against wild-type and drug-resistant hepatitis B virus mutants

被引：20
|
作者：
Wang, Jianing
Singh, Uma S.
Rawal, Ravindra K.
Sugiyama, Massaya [2 ]
Yoo, Jakyung
Jha, Ashok K.
Scroggin, Melissa
Huang, Zhuhui [3 ]
Murray, Michael G. [3 ]
Govindarajan, Rajgopal
Tanaka, Yasuhito [2 ]
Korba, Brent [4 ]
Chu, Chung K. [1 ]
机构：
[1] Univ Georgia, Coll Pharm, Dept Pharmaceut & Biomed Sci, Athens, GA 30602 USA
[2] Nagoya City Univ, Grad Sch Med Sci, Nagoya, Aichi 4678601, Japan
[3] So Res Inst, Frederick, MD 21701 USA
[4] Georgetown Univ, Med Ctr, Washington, DC 20057 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 21期
基金：
新加坡国家研究基金会;
关键词：
Carbocyclic nucleoside; anti-HBV; Drug-resistant; ENTECAVIR RESISTANCE; NUCLEOSIDE ANALOGS; MECHANISM; EFFICACY;
D O I：
10.1016/j.bmcl.2011.08.113
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Novel 2'-fluoro-6'-methylene-carbocyclic adenosine (9) was synthesized and evaluated its anti-HBV activity. The titled compound demonstrated significant antiviral activity against wild-type as well as lamivudine, adefovir and double lamivudine/entecavir resistant mutants. Molecular modeling study indicate that the 2'-fluoro moiety by a hydrogen bond, as well as the van der Waals interaction of the carbocyclic ring with the phenylalanine moiety of the polymerase promote the positive binding, even in the drug resistant mutants. Published by Elsevier Ltd.
引用
收藏
页码：6328 / 6331
页数：4
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