1. Academic Validation
  2. 5'-O-masked 2'-deoxyadenosine analogues as lead compounds for hepatitis C virus (HCV) therapeutic agents

5'-O-masked 2'-deoxyadenosine analogues as lead compounds for hepatitis C virus (HCV) therapeutic agents

  • Bioorg Med Chem. 2007 Nov 15;15(22):6882-92. doi: 10.1016/j.bmc.2007.08.025.
Masahiro Ikejiri 1 Takayuki Ohshima Keizo Kato Masaaki Toyama Takayuki Murata Kunitada Shimotohno Tokumi Maruyama
Affiliations

Affiliation

  • 1 Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan.
Abstract

On the basis of our previous study on Antiviral agents against the severe acute respiratory syndrome (SARS) coronavirus, a series of nucleoside analogues whose 5'-hydroxyl groups are masked by various protective groups such as carboxylate, sulfonate, and ether were synthesized and evaluated to develop novel anti-hepatitis C virus (HCV) agents. Among these, several 5'-O-masked analogues of 6-chloropurine-2'-deoxyriboside (e.g., 5'-O-benzoyl, 5'-O-p-methoxybenzoyl, and 5'-O-benzyl analogues) were found to exhibit effective anti-HCV activity. In particular, the 5'-O-benzoyl analogue exhibited the highest potency with an EC(50) of 6.1 microM in a cell-based HCV replicon assay. Since the 5'-O-unmasked analogue (i.e., 6-chloropurine-2'-deoxyriboside) was not sufficiently potent (EC(50)=47.2 microM), masking of the 5'-hydroxyl group seems to be an effective method for the development of anti-HCV agents. Presently, we hypothesize two roles for the 5'-O-masked analogues: One is the role as an anti-HCV agent by itself, and the Other is as a prodrug of its 5'-O-demasked (deprotected) derivative.

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