Co-reporter:Ian T. Crosby, David G. Bourke, Eric D. Jones, Tyrone P. Jeynes, Susan Cox, Jonathan A.V. Coates, Alan D. Robertson
Bioorganic & Medicinal Chemistry Letters 2011 Volume 21(Issue 6) pp:1644-1648
Publication Date(Web):15 March 2011
DOI:10.1016/j.bmcl.2011.01.109
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.