Methods and compositions for treating hepatitis c virus

A method for the treatment of a hepatitis C virus infection in a host, comprising administering to the host an anti-virally effective amount of a compound of Formula X or XI:

• or a pharmaceutically acceptable salt or ester thereof;
• wherein:
• Base is a pyrimidine base;
• R1, R2, and R3 are each independently H, phosphate, monophosphate, diphosphate, triphosphoate, a stabilized phosphate prodrug, acyl, lower acyl, alkyl, lower alkyl, or a pharmaceutically acceptable leaving group which, when administered in vivo, provides a compound wherein R1, R2, and R3 are each independently H or phosphate;
• R6 is hydrogen, hydroxy, alkyl, lower 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), halo, NO2, NH2, —NH(lower alkyl), —NH(acyl), —N(lower alkyl)2, or —N(acyl)2;
• R7 is hydrogen, OR3, hydroxy, alkyl, lower 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), halo, NO2, NH2, —NH(lower alkyl), —NH(acyl), —N(lower alkyl)2, or —N(acyl)2;
• X is O, S, SO2, or CH2.

A method for inhibiting the replication of a hepatitis C virus in a host, comprising contacting the host with an anti-virally effective amount of a compound of Formula XVII:

• or a pharmaceutically acceptable salt or ester thereof;
• wherein:
• Base is a pyrimidine base;
• R1 and R2 are each independently H, phosphate, monophosphate, diphosphate, triphosphoate, a stabilized phosphate prodrug, acyl, lower acyl, alkyl, lower alkyl, or a pharmaceutically acceptable leaving group which, when administered in vivo, provides a compound wherein R1 and R2 are each independently H or phosphate;
• R6 is hydrogen, hydroxy, alkyl, lower 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), halo, NO2, NH2, —NH(lower alkyl), —NH(acyl), —N(lower alkyl)2, or —N(acyl)2;
• R7 and R9 are each independently hydrogen, OR2, hydroxy, alkyl, lower 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), chloro, bromo, iodo, NO2, NH2, —NH(lower alkyl), —NH(acyl), —N(lower alkyl)2, or —N(acyl)2;
• R10 is H, alkyl, lower alkyl, or halo;
• alternatively, R7 and R9, or R7 and R10 can come together to form a bond;
• and
• X is O, S, SO2, or CH2.

A method for inhibiting the replication of a hepatitis C virus in a host, comprising contacting the host with an anti-virally effective amount of a compound of Formula X or XI:

• or a pharmaceutically acceptable salt or ester thereof;
• wherein:
• Base is a pyrimidine base;
• R1, R2, and R3 are each independently H, phosphate, monophosphate, diphosphate, triphosphoate, a stabilized phosphate prodrug, acyl, lower acyl, alkyl, lower alkyl, or a pharmaceutically acceptable leaving group which, when administered in vivo, provides a compound wherein R1, R2, and R3 are each independently H or phosphate;
• R6 is hydrogen, hydroxy, alkyl, lower 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), halo, NO2, NH2, —NH(lower alkyl), —NH(acyl), —N(lower alkyl)2, or —N(acyl)2;
• R7 is hydrogen, OR3, hydroxy, alkyl, lower 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), halo, NO2, NH2, —NH(lower alkyl), —NH(acyl), —N(lower alkyl)2, or —N(acyl)2;
• X is O, S, SO2, or CH2.

A method for inhibiting the replication of a hepatitis C virus in a host, comprising contacting a polymerase of the host with an anti-virally effective amount of a compound of Formula XVII:

• or a pharmaceutically acceptable salt or ester thereof;
• wherein:
• Base is a pyrimidine base;
• R1 and R2 are each independently H, phosphate, monophosphate, diphosphate, triphosphoate, a stabilized phosphate prodrug, acyl, lower acyl, alkyl, lower alkyl, or a pharmaceutically acceptable leaving group which, when administered in vivo, provides a compound wherein R1 and R2 are each independently H or phosphate;
• R6 is hydrogen, hydroxy, alkyl, lower 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), halo, NO2, NH2, —NH(lower alkyl), —NH(acyl), —N(lower alkyl)2, or —N(acyl)2;
• R7 and R9 are each independently hydrogen, OR2, hydroxy, alkyl, lower 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), chloro, bromo, iodo, NO2, NH2, —NH(lower alkyl), —NH(acyl), —N(lower alkyl)2, or —N(acyl)2;
• R10 is H, alkyl, lower alkyl, or halo;
• alternatively, R7 and R9, or R7 and R10 can come together to form a bond;
• and
• X is O, S, SO2, or CH2.

A method for inhibiting the replication of a hepatitis C virus in a host, comprising contacting a polymerase of the host with an anti-virally effective amount of a compound of Formula X or XI:

• or a pharmaceutically acceptable salt or ester thereof;
• wherein:
• Base is a pyrimidine base;
• R1, R2, and R3 are each independently H, phosphate, monophosphate, diphosphate, triphosphoate, a stabilized phosphate prodrug, acyl, lower acyl, alkyl, lower alkyl, or a pharmaceutically acceptable leaving group which, when administered in vivo, provides a compound wherein R1, R2, and R3 are each independently H or phosphate;
• R6 is hydrogen, hydroxy, alkyl, lower 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), halo, NO2, NH2, —NH(lower alkyl), —NH(acyl), —N(lower alkyl)2, or —N(acyl)2;
• R7 is hydrogen, OR3, hydroxy, alkyl, lower 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), halo, NO2, NH2, —NH(lower alkyl), —NH(acyl), —N(lower alkyl)2, or —N(acyl)2;
• X is O, S, SO2, or CH2.