Synthesis and Antiviral Evaluation of 3'-Fluoro-5'-norcarbocyclic Nucleoside Phosphonates Bearing Uracil and Cytosine as Potential Antiviral Agents.

Pierre-Yves Geant,Christian Périgaud,Jean-Pierre Uttaro,Christophe Mathé

doi:10.3390/molecules25163708

Abstract

Carbocyclic nucleoside analogues are an essential class of antiviral agents and are commonly used in the treatment of viral diseases (hepatitis B, AIDS). Recently, we reported the racemic synthesis and the anti-human immunodeficiency virus activities (HIV) of 3′-fluoro-5′-norcarbocyclic nucleoside phosphonates bearing purines as heterocyclic base. Based on these results, the corresponding racemic norcarbocyclic nucleoside phosphonates bearing pyrimidine bases were synthesized. The prepared compounds were evaluated against HIV, but none of them showed marked antiviral activity compared to their purine counterparts.

Highlights

Nucleoside analogues have been an important part of the therapeutic arsenal used in the treatment of viral diseases for several years [1]
As illustrated with the approval of carbocyclic nucleosides such as abacavir and entecavir as anti-human immunodeficiency virus activities (HIV) and anti-HBV drugs, respectively, the design and synthesis of novel carbocyclic scaffolds could lead to the discovery of new antiviral agents [2,3]
50 -norcarbocyclic nucleoside phosphonates [4,5] as potential anti-viral agents, we have described the synthesis and the anti-HIV activities of 30 -fluoro-50 -norcarbocyclic nucleoside phosphonates bearing purines as heterocyclic base (Figure 1) [6]

Summary

Introduction

Nucleoside analogues have been an important part of the therapeutic arsenal used in the treatment of viral diseases for several years [1]. 50 -norcarbocyclic nucleoside phosphonates [4,5] as potential anti-viral agents, we have described the synthesis and the anti-HIV activities of 30 -fluoro-50 -norcarbocyclic nucleoside phosphonates bearing purines as heterocyclic base (Figure 1) [6]. In such structures, the presence of a P-C bond instead of the hydrolysable P-O induces a metabolic stability of the linkage mimicking the phosphate moiety. Exampleof ofantiviral antiviralcarbocyclic carbocyclicnucleosides nucleosidesand andstructures structuresof of the target compounds

Results

Reagents

Antiviral Evaluation

General Information

Antiviral Activity