title: Antiviral agents 3. Discovery of a novel small molecule non-nucleoside inhibitor of hepatitis B virus (HBV).
abstract: The discovery of a small molecule non-nucleoside inhibitor of Hepatitis B Virus is described. During our work on conocurvone derived naphthoquinone 'trimers' for the treatment of HIV, we discovered a potent inhibitor 9 of Hepatitis B Virus in an antiviral screen. During attempts to resynthesis 9 for proof of concept studies, we altered the synthesis in order to attempt to reduced side reactions and difficult to remove by-products. As a result we discovered a small molecule 19 that also was a potent inhibitor of HBV. Importantly, this small molecule inhibitor of Hepatitis B Virus is also an inhibitor of Hepatitis B Virus resistant to 3TC, a bench mark of nucleoside analogues active in the treatment of Hepatitis B Virus. The development of 19 as an agent to treat HBV infections is discussed.
authors.affiliation: Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia. ian.crosby@monash.edu
authors.forename: Ian T
authors.initials: IT
authors.lastname: Crosby
authors.forename: David G
authors.initials: DG
authors.lastname: Bourke
authors.forename: Eric D
authors.initials: ED
authors.lastname: Jones
authors.forename: Tyrone P
authors.initials: TP
authors.lastname: Jeynes
authors.forename: Susan
authors.initials: S
authors.lastname: Cox
authors.forename: Jonathan A V
authors.initials: JA
authors.lastname: Coates
authors.forename: Alan D
authors.initials: AD
authors.lastname: Robertson
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D055808:Drug Discovery; D006515:Hepatitis B virus / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents