Antiviral agents 3. Discovery of a novel small molecule non-nucleoside inhibitor of Hepatitis B Virus (HBV)

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...

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Bibliographic Details
Published in:	Bioorganic & medicinal chemistry letters Vol. 21; no. 6; pp. 1644 - 1648
Main Authors:	Crosby, Ian T., Bourke, David G., Jones, Eric D., Jeynes, Tyrone P., Cox, Susan, Coates, Jonathan A.V., Robertson, Alan D.
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier Ltd 15-03-2011 Elsevier
Subjects:	Animals Anti-HBV activity Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Antiviral Agents - chemistry Antiviral Agents - pharmacology AZT resistant HBV Biological and medical sciences byproducts chemistry Conocurvone Drug Discovery Hepatitis B virus Hepatitis B virus - drug effects Hepatitis inhibition Medical sciences Naphthoquinone trimers nucleosides Pharmacology. Drug treatments Conocurvone AZT resistant HBV Naphthoquinone trimers Anti-HBV activity Hepatitis inhibition Non nucleoside compound Liver Orthohepadnavirus Hepatitis Hepadnaviridae Antiviral Inhibition Small molecule Hepatitis B virus Chemical synthesis Tumor cell Human Trimer Quinone Naphthoquinone derivatives In vitro Biological activity Virus Resistance Cell line Zidovudine
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Summary:	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.
Bibliography:	http://dx.doi.org/10.1016/j.bmcl.2011.01.109 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2011.01.109