Ribonucleoside cyclic acetal derivatives for the treatment...

C - Chemistry – Metallurgy – 07 – H

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C07H 19/167 (2006.01) A61K 31/7064 (2006.01) A61P 31/14 (2006.01) C07H 19/067 (2006.01)

Patent

CA 2618560

The present invention provides ribonucleoside 2~,3~-cyclic acetals of structural formula I which are precursors or prodrugs of inhibitors of RNA- dependent RNA viral polymerase. These compounds are precursors of inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA- dependent RNA viral infection. They are particularly useful as precursors or prodrugs of inhibitors of hepatitis C virus (HCV) NS5B polymerase, as precursors or prodrugs of inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such ribonucleoside 2~,3~-cyclic acetals alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the ribonucleoside 2~,3~-cyclic acetals of the present invention.

L'invention concerne des acétaux 2',3'-cycliques de ribonucléosides de formule (I) qui sont des précurseurs ou des promédicaments d'inhibiteurs de l'ARN polymérase ARN dépendante virale. Ces composés sont des précurseurs d'inhibiteurs de la réplication virale d'ARN ARN dépendante, et sont utiles pour traiter une infection virale d'ARN ARN dépendante. Ils sont particulièrement utiles en tant que précurseurs ou que promédicaments d'inhibiteurs de la polymérase NS5B du virus de l'hépatite C (HCV), en tant qu'inhibiteurs ou que promédicaments d'inhibiteurs de la réplication de HCV, et/ou pour le traitement d'une infection de l'hépatite C. L'invention concerne également des compositions pharmaceutiques contenant de tels acétaux 2',3'-cycliques de ribonucléosides seuls ou combinés à d'autres agents actifs contre l'infection virale d'ARN ARN dépendante, en particulier une infection HCV. L'invention concerne des méthodes d'inhibition de la polymérase de l'ARN ARN dépendante, d'inhibition d'une réplication virale de l'ARN ARN dépendante, et/ou de traitement d'une infection virale d'ARN ARN dépendante à l'aide des acétaux 2',3'-cycliques de ribunucléosides de l'invention.

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