Modified 2' and 3'-nucleoside prodrugs for treating flaviviridae infections

A method for the treatment of a host infected with a Flaviviridae virus, comprising administering to the host an effective treatment amount of a compound of Formula (IX):

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 and R2 are independently H;
• monophosphate;
• diphosphate;
• triphosphate;
• a stabilized phosphate, straight chained, branched or cyclic alkyl;
• acyl;
• CO-alkyl;
• CO-aryl;
• CO-alkoxyalkyl;
• CO-aryloxyalkyl;
• CO-substituted aryl;
• sulfonate ester;
• benzyl, wherein the phenyl group is optionally substituted with one or more substituents;
• alkylsulfonyl;
• arylsulfonyl;
• aralkylsulfonyl;
• a lipid;
• an amino acid;
• a carbohydrate;
• a peptide;
• cholesterol;
• or a pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R1 and/or R2 is independently H or phosphate;
• X is O, S, SO2 or CH2;
• Base* is a purine or pyrimidine base;
• R12 is C(Y3)3;
• Y3 is independently H, F, Cl, Br or I;
• and
• R13 is fluoro;
• in combination or alternation with a second anti-viral agent.

A method for the treatment of a host infected with a Flaviviridae virus, comprising administering to the host an effective treatment amount of a compound of the formula:

• or a pharmaceutically acceptable salt thereof, wherein:
• Base is selected from the group consisting of adenine, N6-alkylpurine, N6-acylpurine, N6-benzylpurine, N6-halopurine, N6-vinylpurine, N6-acetylenic purine, N6-hydroxyalkyl purine, N6-thioalkyl purine, N2-alkylpurine, thymine, cytosine, 5-fluorocytosine, 5-methylcytosine, 6-azapyrimidine, 6-azacytosine, 2- and/or 4-mercaptopyrimidine, uracil, 5-halouracil, 5-fluorouracil, C5-alkylpyrimidine, C5-benzylpyrimidine, C5-halopyrimidine, C5-vinylpyrimidine, C5-acetylenic pyrimidine, C5-acyl pyrimidine, C5-hydroxyalkyl purine, C5-amidopyrimidine, C5-cyanopyrimidine, C5-nitropyrimidine, C5-amino-pyrimidine, N2-alkylpurine, N2-alkyl-6-thiopurine, 5-azacytidinyl, 5-azauracilyl, triazolopyridinyl, imidazolopyridinyl, pyrrolopyrimidinyl, pyrazolopyrimidinyl, guanine, hypoxanthine, 2,6-diaminopurine, and 6-chloropurine;
• R7 is F;
• R1 is H;
• 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 R1 is H or phosphate;
• R2 is 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 R2 is H or phosphate;
• and
• Y3 is independently H, F, Cl, Br or I.

A method for the treatment of a host infected with a Flaviviridae virus, comprising administering to the host an effective treatment amount of a compound of the formula:

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 and R2 are independently H;
• monophosphate;
• diphosphate;
• triphosphate;
• a stabilized phosphate prodrug;
• straight chained, branched or cyclic alkyl;
• acyl;
• CO-alkyl;
• CO-aryl;
• CO-alkoxyalkyl;
• CO-aryloxyalkyl;
• CO-substituted aryl;
• sulfonate ester;
• alkylsulfonyl;
• arylsulfonyl;
• aralkylsulfonyl;
• a lipid;
• an amino acid;
• a carbohydrate;
• a peptide;
• or a cholesterol;
• X is O;
• Base* is a purine or pyrimidine base;
• R12 is C(Y3)3;
• each Y3 is H;
• and
• R13 is fluoro.