Synthesis and Biological Activity of 7-Deaza-7-ethynyl-2'-deoxy-2'-fluoro-2'-C-methyladenosine and its 2'-C-Methyl-ribo Analogue
Year: 2008
Type: conference-paper
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.
Source: Nucleic Acids Symposium Series
DOI: 10.1093/nass/nrn325
Authors: M. Prhavc, N. Dyatkina, J. Keicher, S. Liehr, S. Koo-McCoy, D. Latour, K. Fung, K. Dunlop, J. Pouliot, T. Wang, W. Li, L. Lou, C. Roberts, R. Griffith
Language: English
Topic: Hepatitis C virus research
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2019114019