Methods and compositions for treating hepatitis C virus
View Patent ↗A method and composition for treating a host infected with hepatitis C comprising administering an effective hepatitis C treatment amount of a described 1′, 2′ or 3′-modified nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided.
1. A method for the treatment of a hepatitis C virus infection in a host, comprising contacting a cell infected with a hepatitis C virus an effective amount of a compound of the formula:
or a mono-, di- or tri-phosphate thereof, or a pharmaceutically acceptable salt or ester thereof, wherein
R 1 ′, R 2 and R 3 are each independently H; phosphate or a stabilized phosphate prodrug;
acyl; 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 each independently H; straight chained, branched or cyclic alkyl; CO-alkyl; CO-aryl; CO-alkoxyalkyl; chloro; bromo; fluoro; iodo; OR 4 ; NR 4 R 5 or SR 5 ; and R 4 and R 5 are independently hydrogen; acyl; or alkyl.
2. A method for the treatment of a hepatitis C virus infection in a host, comprising contacting a cell infected with a hepatitis C virus an effective amount of a compound of the formula:
or a mono-, di- or tri-phosphate thereof, or a pharmaceutically acceptable salt or ester thereof, wherein
R 1 , R 2 and R 3 are each independently H; phosphate or a stabilized phosphate prodrug; acyl; 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 H; straight chained alkyl; branched alkyl; cyclic alkyl; CO-alkyl; CO-aryl; CO-alkoxyalkyl; chloro; bromo; fluoro; iodo; OR 4 ; NR 4 R 5 or SR 5 ; and R 4 and R 5 are independently hydrogen; acyl; or alkyl.
3. The method of claim 1 , wherein the compound has the structure:
or a mono-, di- or tri-phosphate thereof, or a pharmaceutically acceptable salt or ester thereof.
4. The method of claim 1 , wherein the compound has the structure:
or a mono-, di- or tri-phosphate thereof, or a pharmaceutically acceptable salt or ester thereof.
5. The method of claim 1 , wherein the compound has the structure:
or a mono-, di- or tri-phosphate thereof, or a pharmaceutically acceptable salt or ester thereof.
6. The method of claim 2 , wherein the compound has the structure:
or a mono-, di- or tri-phosphate thereof, or a pharmaceutically acceptable salt or ester thereof.
7. The method of claim 2 , wherein the compound has the structure:
or a mono-, di- or tri-phosphate thereof, or a pharmaceutically acceptable salt or ester thereof.
8. The method of claim 2 , wherein the compound has the structure:
or a mono-, di- or tri-phosphate thereof, or a pharmaceutically acceptable salt or ester thereof.
9. A method for the treatment of a hepatitis C virus infection in a host, comprising administering a compound of claim 1 or a pharmaceutically acceptable salt thereof.
10. A method for the treatment of a hepatitis C virus infection in a host, comprising contacting a cell in the host infected with a hepatitis C virus with a compound of claim 1 or a pharmaceutically acceptable salt thereof.
11. A method for the treatment of a hepatitis C virus infection in a host, comprising administering to the host infected with a hepatitis C virus an effective amount of a compound of the formula:
or a mono-, di- or tri-phosphate thereof, or a pharmaceutically acceptable salt or ester thereof, wherein
R 1 ′, R 2 and R 3 are each independently H; phosphate or a stabilized phosphate prodrug; acyl; 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 H; straight chained alkyl; branched alkyl; cyclic alkyl; CO-alkyl; CO-aryl; CO-alkoxyalkyl; chloro; bromo; fluoro; iodo; OR 4 ; NR 4 R 5 or SR S ; and R 4 and R 5 are independently hydrogen; acyl; or alkyl.
12. The method of claim 11 , wherein
R 1 , R 2 and R 3 are each independently H or phosphate;
X 1 is H or CH 3 ; and
Y is hydrogen; bromo; chloro, fluoro; iodo; —NH 2 or -OH.
13. The method of claim 12 , wherein R 1 , R 2 and R 3 are each H.
14. The method of claim 1 , wherein
R 1 is mono-, di- or tri-phosphate; and
R 2 and R 3 are each independently H.
15. The method of claim 11 , wherein
R 1 is mono-, di- or tri-phosphate; and
R 2 and R 3 are each independently H.