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

被引：21

作者：

Crosby, Ian T. ^{[1
]}

Bourke, David G. ^{[1
]}

Jones, Eric D. ^{[1
]}

Jeynes, Tyrone P. ^{[1
]}

Cox, Susan ^{[2
]}

Coates, Jonathan A. V. ^{[2
]}

Robertson, Alan D. ^{[2
]}

机构：

[1] Monash Univ, Monash Inst Pharmaceut Sci, Parkville, Vic 3052, Australia

[2] AMRAD Operat Pty Ltd, Richmond, Vic 3121, Australia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 06期

关键词：

Conocurvone; Naphthoquinone trimers; Anti-HBV activity; Hepatitis inhibition; AZT resistant HBV; TRIMERIC NAPHTHOQUINONE ANALOGS; CONOCURVONE;

D O I：

10.1016/j.bmcl.2011.01.109

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：1644 / 1648

页数：5

共 8 条

[1]

Coates J.A.V., 2005, Australia patent, Patent No. [WO 2005095376, 2005095376]

[2] Antiviral agents. I. Synthesis and antiviral evaluation of trimeric naphthoquinone analogues of conocurvone [J].

Crosby, Ian T. ;

Rose, Mark L. ;

Collis, Maree P. ;

de Bruyn, Paula J. ;

Keep, Philip L. C. ;

Robertson, Alan D. .

AUSTRALIAN JOURNAL OF CHEMISTRY, 2008, 61 (10) :768-784

[3] Antiviral agents 2. Synthesis of trimeric naphthoquinone analogues of conocurvone and their antiviral evaluation against HIV [J].

Crosby, Ian T. ;

Bourke, David G. ;

Jones, Eric D. ;

de Bruyn, Paula J. ;

Rhodes, David ;

Vandegraaff, Nick ;

Cox, Susan ;

Coates, Jonathan A. V. ;

Robertson, Alan D. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2010, 18 (17) :6442-6450

[4] Current Chemical Approaches Directed Toward New and Effective Therapeutic Agents Against Chronic Hepatitis Infections [J].

Hassan, Hammed H. A. M. .

CURRENT ORGANIC CHEMISTRY, 2009, 13 (04) :379-406

[5] USE OF A STANDARDIZED CELL-CULTURE ASSAY TO ASSESS ACTIVITIES OF NUCLEOSIDE ANALOGS AGAINST HEPATITIS-B VIRUS-REPLICATION [J].

KORBA, BE ;

GERIN, JL .

ANTIVIRAL RESEARCH, 1992, 19 (01) :55-70

[6]

KUBO N, 2007, J INFECT CHEMOTHER, V9, P260

[7]

Lau G K, 2001, Clin Liver Dis, V5, P361, DOI 10.1016/S1089-3261(05)70170-7

[8]

Stein Lance L., 2009, Infectious Disorders - Drug Targets, V9, P105

← 1 →