Methods and compositions for treating flaviviruses and pestiviruses

1. A method for the treatment of a flavivirus or pestivirus infection in a host, comprising contacting a cell infected with a flavivirus or a pestivirus with an anti-virally effective amount of a compound of Formula X, XI or XII:

or a phosphate thereof, or a pharmaceutically acceptable salt or ester thereof, wherein:

Base is a purine or pyrimidine base as defined herein;

R 1 , R 2 and R 3 are independently H; phosphate; monophosphate; diphosphate; triphosphate; or a stabilized phosphate prodrug; acyl; alkyl; lower alkyl; sulfonate ester; alkyl sulfonyl; arylalkyl sulfonyl; methanesulfonyl; and benzyl, wherein the phenyl group is optionally substituted with one or more substituents as described in the definition of aryl given herein; a lipid; a phospholipid; an amino acid; a carbohydrate; a peptide; a cholesterol; or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R 1 , R 2 or R 3 is independently H or phosphate;

R 6 is alkyl; or cyano;

R 7 is OR 3 or hydroxy; and

X is O, S, SO 2 or CH 2 .

2. A method for the treatment of a flavivirus or pestivirus infection in a host, comprising contacting a cell infected with a flavivirus or a pestivirus with an anti-virally effective amount of a compound of Formula XVII:

or a phosphate thereof, or a pharmaceutically acceptable salt or ester thereof, wherein:

Base is a purine or pyrimidine base;

R 1 and R 2 are independently H; phosphate; monophosphate; diphosphate; triphosphate; or a stabilized phosphate prodrug; acyl; alkyl; sulfonate ester; alkyl sulfonyl; arylalkyl sulfonyl; methanesulfonyl; and benzyl, wherein the phenyl group is optionally substituted with one or more substituents as described in the definition of aryl given herein; a lipid; a phospholipid; an amino acid; a carbohydrate; a peptide; a cholesterol; or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R 1 or R 2 is independently H or phosphate;

R 6 is alkyl, or cyano;

R 7 is OR 2 or hydroxy;

R 9 is hydrogen, OR 2 , hydroxy, alkyl; azido, cyano, alkenyl, alkynyl, Br-vinyl, —C(O)O(alkyl), —C(O)O(lower alkyl), —O(acyl), —O(lower acyl), —O(alkyl), —O(lower alkyl), —O(alkenyl), chlorine, bromine, iodine, NO 2 , NH 2 , —NH(lower alkyl), —NH(acyl), —N(lower alkyl) 2 , —N(acyl) 2 ;

R 10 is H, alkyl, chlorine, bromine or iodine;

alternatively, R 7 and R 9 , or R 7 and R 10 can come together to form a bond; and

X is O, S, SO 2 or CH 2 .

3. The method of claim 2 , wherein the compound is

or a phosphate thereof, or a pharmaceutically acceptable salt or ester thereof, wherein

R 1 , R 2 and R 3 are independently H; phosphate; monophosphate, diphosphate, triphosphate, a stabilized phosphate prodrug; acyl; alkyl; sulfonate ester; alkyl sulfonyl; arylalkyl sulfonyl; methanesulfonyl; benzylsulfonyl, wherein the phenyl group is optionally substituted with one or more substituents as described in the definition of aryl given herein; a lipid; a phospholipid; an amino acid; a carbohydrate; a peptide; a cholesterol; or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R 1 , R 2 or R 3 is independently H or phosphate;

Y is hydrogen, bromo, chloro, fluoro, iodo, OR 4 , NR 4 R 5 or SR 4 ;

X 1 and X 2 are independently selected from the group consisting of H, straight chained, branched or cyclic alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, chloro, bromo, fluoro, iodo, OR 4 , NR 4 NR 5 or SR 5 ; and

R 4 and R 5 are independently hydrogen, acyl; alkyl; methyl, ethyl, propyl or cyclopropyl.

4. The method of claim 2 , wherein the compound is

or a phosphate thereof, or a pharmaceutically acceptable salt or ester thereof, wherein

R 1 , R 2 and R 3 are independently H; phosphate; monophosphate, diphosphate, triphosphate, a stabilized phosphate prodrug; acyl; alkyl; sulfonate ester; alkyl sulfonyl; arylalkyl sulfonyl; methanesulfonyl; benzylsulfonyl, wherein the phenyl group is optionally substituted with one or more substituents as described in the definition of aryl given herein; a lipid; a phospholipid; an amino acid; a carbohydrate; a peptide; a cholesterol; or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R 1 , R 2 or R 3 is independently H or phosphate;

Y is hydrogen, bromo, chloro, fluoro, iodo, OR 4 , NR 4 R 5 or SR 4 ;

X 1 is selected from the group consisting of H, straight chained, branched or cyclic alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, chloro, bromo, fluoro, iodo, OR 4 , NR 4 NR 5 or SR 5 ; and

R 4 and R 5 are independently hydrogen, acyl; alkyl; methyl, ethyl, propyl or cyclopropyl.

5. The method of claim 2 , wherein the compound is in the form of a dosage unit.

6. The method of claim 5 , wherein the dosage unit contains 10 to 1500 mg of said compound.

7. The method of claim 5 or 6 , wherein said dosage unit is a tablet or capsule.

8. The method of claim 1 , wherein the compound is combined with a pharmaceutically acceptable carrier.

9. The method of claim 8 , wherein the carrier is suitable for oral delivery.

10. The method of claim 9 , wherein the carrier is suitable for intravenous, parenteral, intradermal, subcutaneous or topical delivery.