Abstract
In our search for improved therapeutic agents against HCV we synthesized 7-deaza-7-ethynyl-2'-C-methyladenosine (1) and its 2'-deoxy-2'-fluoro analogue 2. The corresponding nucleoside triphosphates were efficient chain terminators of the HCV NS5b polymerase with IC(50)'s of 0.75 microM and 0.4 microM respectively. However, only the ribo-nucleoside 1 exhibited activity in a Huh7 cell based replicon assay with an EC(50) of 0.09 microM. In order to overcome the lack of activity of the fluoro analogue 2 we synthesised several phosphoroamidate prodrugs.
MeSH terms
-
Antiviral Agents / chemical synthesis*
-
Antiviral Agents / chemistry
-
Antiviral Agents / pharmacology
-
Hepacivirus / drug effects*
-
Prodrugs / chemical synthesis
-
Prodrugs / chemistry
-
Prodrugs / pharmacology
-
Tubercidin / analogs & derivatives*
-
Tubercidin / chemical synthesis
-
Tubercidin / chemistry
-
Tubercidin / pharmacology
-
Viral Nonstructural Proteins / antagonists & inhibitors
Substances
-
7-deaza-7-ethynyl-2'-C-methyladenosine
-
7-deaza-7-ethynyl-2'-deoxy-2'-fluoro-2'-C-methyladenosine
-
Antiviral Agents
-
Prodrugs
-
Viral Nonstructural Proteins
-
NS-5 protein, hepatitis C virus
-
Tubercidin