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Synthèse et évaluation de nouveaux nucléosides ciblant l'hépatite C dans un système réplicon

Abstract : Hepatitis C virus is a major health problem, which chronically infects 180 millions people around the world, and can lead to cirrhosis and hepatocellular carcinoma. Only one treatment based on a combination therapy of ribavirin and interferon alpha has been approved, but 50 % of the patients are non-responders to the treatment, which is associated with toxic side effects. Therefore, there is an urgent need for improved therapies against chronic HCV infection. Beside the success of analogues of nucleosides targeting key enzymes involved in the viral replication, only few of them were designed to target ARN dependent ARN polymerase. To achieve this goal, the synthesis of new carbocyclic analogues of ribavirin, and 5-haloethynyl- or 5-(1,2-dihalo)vinyluracile nucleoside analogues, was performed in this thesis, using the Sonogashira reaction or the 1,3-dipolar cycloaddition, two powerful tools of the organic chemistry useful to build new structures and bring further interesting modifications. All derivatives were evaluated for their antiviral activities.
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Contributor : Laurent Robin <>
Submitted on : Monday, February 11, 2008 - 4:25:38 PM
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  • HAL Id : tel-00250329, version 1


Nicolas Joubert. Synthèse et évaluation de nouveaux nucléosides ciblant l'hépatite C dans un système réplicon. Autre. Université d'Orléans, 2006. Français. ⟨tel-00250329⟩



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