Nucleoside aryl phosphoramidates for the treatment of RNA-dependent RNA viral infection

• Main Authors: BARBARA ATTENNI, PHILIPPE L. DURETTE, MONICA DONGHI, CRISTINA GARDELLI, FRANK NARJES
• Format: Patent
• Language: English
• Published: 17.07.2008
• Subjects: AGRICULTURE; ANIMAL HUSBANDRY; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES, AS HERBICIDES; CHEMISTRY; DERIVATIVES THEREOF; FISHING; FORESTRY; HUMAN NECESSITIES; HUNTING; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; NUCLEIC ACIDS; NUCLEOSIDES; NUCLEOTIDES; ORGANIC CHEMISTRY; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTSTHEREOF; SUGARS; TRAPPING

The present invention provides nucleoside aryl phosphoramidates of structural formula (I) which are precursors to inhibitors of RNA-dependent RNA viral polymerase. These compounds are precursors to 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 to inhibitors of hepatitis C virus (HCV) NS5B polymerase, as precursors to inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside aryl phosphoramidates 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 nucleoside aryl phosphoramidates of the present invention. (I)