MODIFIED 2' AND 3'-NUCLEOSIDE PRODRUGS FOR TREATING FLAVIVIRIDAE INFECTIONS
2′ and/or 3′ prodrugs of 1′, 2′, 3′ or 4′-branched nucleosides, and their pharmaceutically acceptable salts and derivatives are described. These prodrugs are useful in the prevention and treatment of Flaviviridae infections, including HCV infection, and other related conditions. Compounds and compositions of the prodrugs of the present invention are described. Methods and uses are also provided that include the administration of an effective amount of the prodrugs of the present invention, or their pharmaceutically acceptable salts or derivatives. These drugs may optionally be administered in combination or alteration with further anti-viral agents to prevent or treat Flaviviridae infections and other related conditions.
1 - 13 . (canceled)
14 . A method for the treatment of a host infected with a hepatitis C virus, comprising administering to the host infected with a hepatitis C virus an effective amount of a compound of the formula:
or a pharmaceutically acceptable salt thereof, wherein:
Base is selected from the group consisting of thymine, cytosine, 5-fluorocytosine, 5-methylcytosine, 6-azapyrimidine, 6-azacytosine, 2- and/or 4-mercaptopyrimidine, uracil, 5-halouracil, 5-fluorouracil, C 5 -alkylpyrimidine, C 5 -benzylpyrimidine, C 5 -halopyrimidine, C 5 -vinylpyrimidine, C 5 -acetylenic pyrimidine, C 5 -acyl pyrimidine, C 5 -amidopyrimidine, C 5 -cyanopyrimidine, C 5 -iodopyrimidine, C 6 -iodo-pyrimidine, C 5 -Br-vinyl pyrimidine, C6-Br-vinyl pyrimidine, C 5 -nitropyrimidine, C 5 -amino-pyrimidine, 5-azacytidinyl, 5-azauracilyl;
R 7 is F;
R 1 is H; phosphate; monophosphate, diphosphate; triphosphate; a stabilized phosphate prodrug; acyl; lower acyl; alkyl; lower alkyl; sulfonate ester; alkyl or arylalkyl sulfonyl; methanesulfonyl; benzylsulfonyl; a lipid; a phospholipid; an amino acid; a carbohydrate; a peptide; a cholesterol; or other pharmaceutically acceptable leaving group which when administered in vivo provides a compound wherein R 1 is H or phosphate;
R 2 is phosphate; monophosphate; diphosphate; triphosphate; a stabilized phosphate prodrug; acyl; lower acyl; alkyl; lower alkyl; sulfonate ester; alkyl or arylalkyl sulfonyl; methanesulfonyl; benzylsulfonyl; a lipid; a phospholipid; an amino acid; a carbohydrate; a peptide; a cholesterol; or other pharmaceutically acceptable leaving group which when administered in vivo provides a compound wherein R 2 is H or phosphate; and
wherein each Y 3 is H.