title: Antiviral activity of novel 2'-fluoro-6'-methylene-carbocyclic adenosine against wild-type and drug-resistant hepatitis B virus mutants.
abstract: 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.
authors.affiliation: The University of Georgia, College of Pharmacy, Athens, GA 30602, USA.
authors.forename: Jianing
authors.initials: J
authors.lastname: Wang
authors.forename: Uma S
authors.initials: US
authors.lastname: Singh
authors.forename: Ravindra K
authors.initials: RK
authors.lastname: Rawal
authors.forename: Masaya
authors.initials: M
authors.lastname: Sugiyama
authors.forename: Massaya
authors.initials: M
authors.lastname: Sugiyama
authors.forename: Jakyung
authors.initials: J
authors.lastname: Yoo
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Jha
authors.forename: Melissa
authors.initials: M
authors.lastname: Scroggin
authors.forename: Zhuhui
authors.initials: Z
authors.lastname: Huang
authors.forename: Michael G
authors.initials: MG
authors.lastname: Murray
authors.forename: Rajgopal
authors.initials: R
authors.lastname: Govindarajan
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Brent
authors.initials: B
authors.lastname: Korba
authors.forename: Chung K
authors.initials: CK
authors.lastname: Chu
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D009154:Mutation
chemical_list: C569519:2'-fluoro-6'-methylene-carbocyclic adenosine; D000998:Antiviral Agents; D000241:Adenosine