Hepatitis C therapies

A compound of the formula:

• wherein:
• R is chloro, methoxy, methylamino, isopropylamino, propylamino, ethylamino, dimethylamino, cyclopropylamino, 2-aminoethylamino, 1-(2-hydroxyethyl)hydrazino, hydrazino, 1-methylhydrazino, azetidino, pyrrolidino, imidazolyipropylamino, pyrrolino, morpholino, piperazino, hydroxyethylamino, bis-hydroxyethylamino, hydroxypropylamino, hydroxyethylpyrrolidino, or 1-methyl-2-hydroxyethylamino;
• n is 0, 1 , 2 , 3, 4, or 5;
• R1 is H, NRaRb, Cl, F, ORa, SRa, NHCORa, NHSO2Ra, NHCONHRa, CN, alkyl, aryl, ONRaRb, or NRaC(O)ORb;
• R2 is H and R3 is OH;
• or R2 is OH and R3 is H;
• R4 is OH, alkyl-O—, alkylC(═O)O, alkyl-S—, or alkylC(═O)—S—;
• R5 is OH, alkyl-O—, alkylC(═O)O, alkyl-S—, or alkylC(═O)—S—
• Ra, Rb, Rc, Rd are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl and NO;
• or Ra and Rb together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• or Rb and Rc together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• Re is alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl or NO;
• and Rf is H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl and NO;
• or Re and Rf together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• which ring is optionally substituted with one or more halo, hydroxyl, alkyl, alkenyl, or alkynyl;
• wherein any alkyl, cycloalkyl, alkenyl, alkynyl, or acyl is optionally substituted with 1 to 3 substituents selected from the group consisting of alkoxy, acyl, acylamino, acyloxy, oxyacyl, amino, substituted amino, aminoacyl, aryl, aryloxy, cyano, halogen, hydroxyl, nitro, N3, carboxyl, carboxyl esters, thiol, thioalkyl, thioaryl, thioheteroaryl, thiocycloalkyl, thioheterocyclic, cycloalkyl, heteroaryl, and heterocyclic;
• and wherein any aryl, heteroaryl, or heterocycle is optionally substituted with 1 to 3 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, acyl, acylamino, acyloxy, oxyacyl, amino, substituted amino, aminoacyl, aryl, aryloxy, cyano, halogen, hydroxyl, nitro, N3, carboxyl, carboxyl esters, thiol, thioalkyl, thioaryl, thioheteroaryl, thiocycloalkyl, thioheterocyclic, cycloalkyl, heteroaryl, and heterocyclic;
• or a pharmaceutically acceptable salt or prodrug thereof.

A compound of the formula:

• wherein:
• R is NReRf;
• n is 0, 1, 2, 3, 4, or 5;
• R1 is H, NRaRb, Cl, F, ORa, SRa, NHCORa, NHSO2Ra, NHCONHRa, CN, alkyl, aryl, ONRaRb, or NRaC(O)ORb;
• R2 is H and R3 is OH;
• or R2 is OH and R3 is H;
• R4 is OH, alkyl-O—, alkylC(═O)O, alkyl-S—, or alkylC(═O)—S—;
• R5 is OH, alkyl-O—, alkylC(═O)O, alkyl-S—, or alkylC(═O)—S—
• Ra, Rb, Rc, Rd are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl and NO;
• or Ra and Rb together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• or Rb and Rc together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• Re is alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl or NO;
• and Rf is H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl and NO;
• or Re and Rf together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• which ring is optionally substituted with one or more halo, hydroxyl, alkyl, alkenyl, or alkynyl;
• wherein any alkyl, cycloalkyl, alkenyl, alkynyl, or acyl is optionally substituted with 1 to 3 substituents selected from the group consisting of alkoxy, acyl, acylamino, acyloxy, oxyacyl, amino, substituted amino, aminoacyl, aryl, aryloxy, cyano, halogen, hydroxyl, nitro, N3, carboxyl, carboxyl esters, thiol, thioalkyl, thioaryl, thioheteroaryl, thiocycloalkyl, thioheterocyclic, cycloalkyl, heteroaryl, and heterocyclic;
• and wherein any aryl, heteroaryl, or heterocycle is optionally substituted with 1 to 3 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, acyl, acylamino, acyloxy, oxyacyl, amino, substituted amino, aminoacyl, aryl, aryloxy, cyano, halogen, hydroxyl, nitro, N3, carboxyl, carboxyl esters, thiol, thioalkyl, thioaryl, thioheteroaryl, thiocycloalkyl, thioheterocyclic, cycloalkyl, heteroaryl, and heterocyclic;
• or a pharmaceutically acceptable salt or prodrug thereof.

The compound 4-methylamino-7-β-(D-ribofuranosyl)-furo[3,2-d]pyrimidine;

• 4-Ethylamino-7-β-(D-ribofuranosyl)-furo[3,2-d]pyrimidine;
• 4-Isopropylamino-7-β-(D-ribofuranosyl)-furo[3,2-d]pyrimidine;
• 4-Dimethylamino-7-β-(D-ribofuranosyl)-furo[3,2-d]pyrimidine;
• 4-n-Propylamino-7-β-(D-ribofuranosyl)-furo[3,2-d]pyrimidine;
• 4-(N-3-pyrrolino)-7-β-(D-ribofuranosyl)-furo[3,2-d]pyrimidine;
• 4-(2-hydroxymethylpyrrolidino)-7-β-(D-ribofuranosyl)-furo[3,2-d]pyrimidine;
• 4-(3-N-imidazolyl-n-propylamino)-7-β-(D-ribofuranosyl)-furo[3,2-d]pyrimidine;
• 4-N-morpholino-7-β-(D-ribofuranosyl)-furo[3,2-d]pyrimidine;
• 4-N-piperazino-7-β-(D-ribofuranosyl)-furo[3,2-d]pyrimidine;
• 4-(hydroxyethylamino)-7-β-(D-ribofuranosyl)-furo[3,2-d]pyrimidine;
• 4-(N-bis-hydroxyethylamino)-7-β-(D-ribofuranosyl)-furo[3,2-d]pyrimidine;
• 4-(3-hydroxypropylamino)-7-β-(D-ribofuranosyl)-furo[3,2-d]pyrimidine;
• or 4-(2-hydroxy-1-methyl-ethylamino)-7-β-(D-ribofuranosyl)-furo[3,2-d]pyrimidine;
• or a pharmaceutically acceptable salt or prodrug thereof.

A prodrug of a compound of the formula:

• wherein:
• R is ORa, SRa, NReRf, NRaNRbRc, alkyl, alkenyl, alkynyl, aryl, (CH2)nNRaRb, (CH2)nORa, C(═NRa)NRbRc, (CH2)n—CH(NHRa)CO2Rb, (CH2)n—S-alkyl, (CH2)n—S-aryl, Cl, F, Br, I, CN, COORa, CONRaRb, NHC(═NRa)NHRb, NRaORb, NRaNO, NHCONHRa, NRaN═NRb, NRaN═CHRb, NRaC(O)NRbRc, NRaC(S)NRbRc, NRaC(O)ORb, CH═N—ORa, NRaC(═NH)NRbRc, NRaC(O)NRbNRcRd, O—C(O)Ra, OC(O)—ORa, ONH—C(O)O-alkyl, ONHC(O)O-aryl, ONRaRb, SNRaRb, S—ONRaRb, or SO2NRaRb;
• n is 0, 1, 2, 3, 4, or 5;
• R1 is H, NRaRb, Cl, F, ORa, SRa, NHCORa, NHSO2Ra, NHCONHRa, CN, alkyl, aryl, ONRaRb, or NRaC(O)ORb;
• R2 is H and R3 is OH;
• or R2 is OH and R3 is H;
• R4 is OH, alkyl-O—, alkylC(═O)O, alkyl-S—, or alkylC(═O)—S—;
• R5 is OH, alkyl-O—, alkylC(═O)O, alkyl-S—, or alkylC(═O)—S—
• Ra, Rb, Rc, Rd are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl and NO;
• or Ra and Rb together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• or Rb and Rc together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• Re is alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl or NO;
• and Rf is H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl and NO;
• or Re and Rf together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• which ring is optionally substituted with one or more halo, hydroxyl, alkyl, alkenyl, or alkynyl;
• wherein any alkyl, cycloalkyl, alkenyl, alkynyl, or acyl is optionally substituted with 1 to 3 substituents selected from the group consisting of alkoxy, acyl, acylamino, acyloxy, oxyacyl, amino, substituted amino, aminoacyl, aryl, aryloxy, cyano, halogen, hydroxyl, nitro, N3, carboxyl, carboxyl esters, thiol, thioalkyl, thioaryl, thioheteroaryl, thiocycloalkyl, thioheterocyclic, cycloalkyl, heteroaryl, and heterocyclic;
• and wherein any aryl, heteroaryl, or heterocycle is optionally substituted with 1 to 3 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, acyl, acylamino, acyloxy, oxyacyl, amino, substituted amino, aminoacyl, aryl, aryloxy, cyano, halogen, hydroxyl, nitro, N3, carboxyl, carboxyl esters, thiol, thioalkyl, thioaryl, thioheteroaryl, thiocycloalkyl, thioheterocyclic, cycloalkyl, heteroaryl, and heterocyclic.

A pharmaceutical composition comprising a compound:

• wherein:
• R is ORa, SRa, NReRf, NRaNRbRc, alkyl, alkenyl, alkynyl, aryl, (CH2)nNRaRb, (CH2)nORa, C(═NRa)NRbRc, (CH2)n—CH(NHRa)CO2Rb, (CH2)n—S-alkyl, (CH2)n—S-aryl, Cl, F, Br, I, CN, COORa, CONRaRb, NHC(═NRa)NHRb, NRaORb, NRaNO, NHCONHRa, NRaN═NRb, NRaN═CHRb, NRaC(O)NRbRc, NRaC(S)NRbRc, NRaC(O)ORb, CH═N—ORa, NRaC(═NH)NRbRc, NRaC(O)NRbNRcRd, O—C(O)Ra, OC(O)—ORa, ONH—C(O)O-alkyl, ONHC(O)O-aryl, ONRaRb, SNRaRb, S—ONRaRb, or SO2NRaRb;
• n is 0, 1, 2, 3, 4, or 5;
• R1 is H, NRaRb, Cl, F, ORa, SRa, NHCORa, NHSO2Ra, NHCONHRa, CN, alkyl, aryl, ONRaRb, or NRaC(O)ORb;
• R2 is H and R3 is OH;
• or R2 is OH and R3 is H;
• R4 is OH, alkyl-O—, alkylC(═O)O, alkyl-S—, or alkylC(═O)—S—;
• R5 is OH, alkyl-O—, alkylC(═O)O, alkyl-S—, or alkylC(═O)—S—
• Ra, Rb, Rc, Rd are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl and NO;
• or Ra and Rb together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• or Rb and Rc together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• Re is alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl or NO;
• and Rf is H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl and NO;
• or Re and Rf together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• which ring is optionally substituted with one or more halo, hydroxyl, alkyl, alkenyl, or alkynyl;
• wherein any alkyl, cycloalkyl, alkenyl, alkynyl, or acyl is optionally substituted with 1 to 3 substituents selected from the group consisting of alkoxy, acyl, acylamino, acyloxy, oxyacyl, amino, substituted amino, aminoacyl, aryl, aryloxy, cyano, halogen, hydroxyl, nitro, N3, carboxyl, carboxyl esters, thiol, thioalkyl, thioaryl, thioheteroaryl, thiocycloalkyl, thioheterocyclic, cycloalkyl, heteroaryl, and heterocyclic;
• and wherein any aryl, heteroaryl, or heterocycle is optionally substituted with 1 to 3 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, acyl, acylamino, acyloxy, oxyacyl, amino, substituted amino, aminoacyl, aryl, aryloxy, cyano, halogen, hydroxyl, nitro, N3, carboxyl, carboxyl esters, thiol, thioalkyl, thioaryl, thioheteroaryl, thiocycloalkyl, thioheterocyclic, cycloalkyl, heteroaryl, and heterocyclic.
• or a pharmaceutically acceptable salt or prodrug thereof;
• and a pharmacuetically acceptable carrier;
• which further comprises one or more additional anti-viral agents, immune modulators, or interferon inducers.

A pharmaceutical composition comprising a compound:

• wherein:
• R is ORa, SRa, NReRf, NRaNRbRc, alkyl, alkenyl, alkynyl, aryl, (CH2)nNRaRb, (CH2)nORa, C(═NRa)NRbRc, (CH2)n—CH(NHRa)CO2Rb, (CH2)n—S-alkyl, (CH2)n—S-aryl, Cl, F, Br, I, CN, COORa, CONRaRb, NHC(═NRa)NHRb, NRaORb, NRaNO, NHCONHRa, NRaN═NRb, NRaN═CHRb, NRaC(O)NRbRc, NRaC(S)NRbRc, NRaC(O)ORb, CH═N—ORa, NRaC(═NH)NRbRc, NRaC(O)NRbNRcRd, O—C(O)Ra, OC(O)—ORa, ONH—C(O)O-alkyl, ONHC(O)O-aryl, ONRaRb, SNRaRb, S—ONRaRb, or SO2NRaRb;
• n is 0, 1, 2, 3, 4, or 5;
• R1 is H, NRaRb, Cl, F, ORa, SRa, NHCORa, NHSO2Ra, NHCONHRa, CN, alkyl, aryl, ONRaRb, or NRaC(O)ORb;
• R2 is H and R3 is OH;
• or R2 is OH and R3 is H;
• R4 is OH, alkyl-O—, alkylC(═O)O, alkyl-S—, or alkylC(═O)—S—;
• R5 is OH, alkyl-O—, alkylC(═O)O, alkyl-S—, or alkylC(═O)—S—
• Ra, Rb, Rc, Rd are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl and NO;
• or Ra and Rb together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• or Rb and Rc together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• Re is alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl or NO;
• and Rf is H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl and NO;
• or Re and Rf together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• which ring is optionally substituted with one or more halo, hydroxyl, alkyl, alkenyl, or alkynyl;
• wherein any alkyl, cycloalkyl, alkenyl, alkynyl, or acyl is optionally substituted with 1 to 3 substituents selected from the group consisting of alkoxy, acyl, acylamino, acyloxy, oxyacyl, amino, substituted amino, aminoacyl, aryl, aryloxy, cyano, halogen, hydroxyl, nitro, N3, carboxyl, carboxyl esters, thiol, thioalkyl, thioaryl, thioheteroaryl, thiocycloalkyl, thioheterocyclic, cycloalkyl, heteroaryl, and heterocyclic;
• and wherein any aryl, heteroaryl, or heterocycle is optionally substituted with 1 to 3 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, acyl, acylamino, acyloxy, oxyacyl, amino, substituted amino, aminoacyl, aryl, aryloxy, cyano, halogen, hydroxyl, nitro, N3, carboxyl, carboxyl esters, thiol, thioalkyl, thioaryl, thioheteroaryl, thiocycloalkyl, thioheterocyclic, cycloalkyl, heteroaryl, and heterocyclic.
• or a pharmaceutically acceptable salt or prodrug thereof;
• and a pharmacuetically acceptable carrier;
• which further comprises one or more additional HCV polymerase inhibitors.

A pharmaceutical composition comprising a compound:

• wherein:
• R is ORa, SRa, NReRf, NRaNRbRc, alkyl, alkenyl, alkynyl, aryl, (CH2)nNRaRb, (CH2)nORa, C(═NRa)NRbRc, (CH2)n—CH(NHRa)CO2Rb, (CH2)n—S-alkyl, (CH2)n—S-aryl, Cl, F, Br, I, CN, COORa, CONRaRb, NHC(═NRa)NHRb, NRaORb, NRaNO, NHCONHRa, NRaN═NRb, NRaN═CHRb, NRaC(O)NRbRc, NRaC(S)NRbRc, NRaC(O)ORb, CH═N—ORa, NRaC(═NH)NRbRc, NRaC(O)NRbNRcRd, O—C(O)Ra, OC(O)—ORa, ONH—C(O)O-alkyl, ONHC(O)O-aryl, ONRaRb, SNRaRb, S—ONRaRb, or SO2NRaRb;
• n is 0, 1, 2, 3, 4, or 5;
• R1 is H, NRaRb, Cl, F, ORa, SRa, NHCORa, NHSO2Ra, NHCONHRa, CN, alkyl, aryl, ONRaRb, or NRaC(O)ORb;
• R2 is H and R3 is OH;
• or R2 is OH and R3 is H;
• R4 is OH, alkyl-O—, alkylC(═O)O, alkyl-S—, or alkylC(═O)—S—;
• R5 is OH, alkyl-O—, alkylC(═O)O, alkyl-S—, or alkylC(═O)—S—
• Ra, Rb, Rc, Rd are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl and NO;
• or Ra and Rb together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• or Rb and Rc together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• Re is alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl or NO;
• and Rf is H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl and NO;
• or Re and Rf together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• which ring is optionally substituted with one or more halo, hydroxyl, alkyl, alkenyl, or alkynyl;
• wherein any alkyl, cycloalkyl, alkenyl, alkynyl, or acyl is optionally substituted with 1 to 3 substituents selected from the group consisting of alkoxy, acyl, acylamino, acyloxy, oxyacyl, amino, substituted amino, aminoacyl, aryl, aryloxy, cyano, halogen, hydroxyl, nitro, N3, carboxyl, carboxyl esters, thiol, thioalkyl, thioaryl, thioheteroaryl, thiocycloalkyl, thioheterocyclic, cycloalkyl, heteroaryl, and heterocyclic;
• and wherein any aryl, heteroaryl, or heterocycle is optionally substituted with 1 to 3 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, acyl, acylamino, acyloxy, oxyacyl, amino, substituted amino, aminoacyl, aryl, aryloxy, cyano, halogen, hydroxyl, nitro, N3, carboxyl, carboxyl esters, thiol, thioalkyl, thioaryl, thioheteroaryl, thiocycloalkyl, thioheterocyclic, cycloalkyl, heteroaryl, and heterocyclic.
• or a pharmaceutically acceptable salt or prodrug thereof;
• and a pharmacuetically acceptable carrier;
• which further comprises one or more protease inhibitors.

A pharmaceutical composition comprising a compound:

• wherein:
• R is ORa, SRa, NReRf, NRaNRbRc, alkyl, alkenyl, alkynyl, aryl, (CH2)nNRaRb, (CH2)nORa, C(═NRa)NRbRc, (CH2)n—CH(NHRa)CO2Rb, (CH2)n—S-alkyl, (CH2)n—S-aryl, Cl, F, Br, I, CN, COORa, CONRaRb, NHC(═NRa)NHRb, NRaORb, NRaNO, NHCONHRa, NRaN═NRb, NRaN═CHRb, NRaC(O)NRbRc, NRaC(S)NRbRc, NRaC(O)ORb, CH═N—ORa, NRaC(═NH)NRbRc, NRaC(O)NRbNRcRd, O—C(O)Ra, OC(O)—ORa, ONH—C(O)O-alkyl, ONHC(O)O-aryl, ONRaRb, SNRaRb, S—ONRaRb, or SO2NRaRb;
• n is 0, 1, 2, 3, 4, or 5;
• R1 is H, NRaRb, Cl, F, ORa, SRa, NHCORa, NHSO2Ra, NHCONHRa, CN, alkyl, aryl, ONRaRb, or NRaC(O)ORb;
• R2 is H and R3 is OH;
• or R2 is OH and R3 is H;
• R4 is OH, alkyl-O—, alkylC(═O)O, alkyl-S—, or alkylC(═O)—S—;
• R5 is OH, alkyl-O—, alkylC(═O)O, alkyl-S—, or alkylC(═O)—S—
• Ra, Rb, Rc, Rd are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl and NO;
• or Ra and Rb together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• or Rb and Rc together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• Re is alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl or NO;
• and Rf is H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl and NO;
• or Re and Rf together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• which ring is optionally substituted with one or more halo, hydroxyl, alkyl, alkenyl, or alkynyl;
• wherein any alkyl, cycloalkyl, alkenyl, alkynyl, or acyl is optionally substituted with 1 to 3 substituents selected from the group consisting of alkoxy, acyl, acylamino, acyloxy, oxyacyl, amino, substituted amino, aminoacyl, aryl, aryloxy, cyano, halogen, hydroxyl, nitro, N3, carboxyl, carboxyl esters, thiol, thioalkyl, thioaryl, thioheteroaryl, thiocycloalkyl, thioheterocyclic, cycloalkyl, heteroaryl, and heterocyclic;
• and wherein any aryl, heteroaryl, or heterocycle is optionally substituted with 1 to 3 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, acyl, acylamino, acyloxy, oxyacyl, amino, substituted amino, aminoacyl, aryl, aryloxy, cyano, halogen, hydroxyl, nitro, N3, carboxyl, carboxyl esters, thiol, thioalkyl, thioaryl, thioheteroaryl, thiocycloalkyl, thioheterocyclic, cycloalkyl, heteroaryl, and heterocyclic.
• or a pharmaceutically acceptable salt or prodrug thereof;
• and a pharmacuetically acceptable carrier;
• which further comprises ribavirin.

A pharmaceutical composition comprising a compound:

• wherein:
• R is ORa, SRa, NReRf, NRaNRbRc, alkyl, alkenyl, alkynyl, aryl, (CH2)nNRaRb, (CH2)nORa, C(═NRa)NRbRc, (CH2)n—CH(NHRa)CO2Rb, (CH2)n—S-alkyl, (CH2)n—S-aryl, Cl, F, Br, I, CN, COORa, CONRaRb, NHC(═NRa)NHRb, NRaORb, NRaNO, NHCONHRa, NRaN═NRb, NRaN═CHRb, NRaC(O)NRbRc, NRaC(S)NRbRc, NRaC(O)ORb, CH═N—ORa, NRaC(═NH)NRbRc, NRaC(O)NRbNRcRd, O—C(O)Ra, OC(O)—ORa, ONH—C(O)O-alkyl, ONHC(O)O-aryl, ONRaRb, SNRaRb, S—ONRaRb, or SO2NRaRb;
• n is 0, 1, 2, 3, 4, or 5;
• R1 is H, NRaRb, Cl, F, ORa, SRa, NHCORa, NHSO2Ra, NHCONHRa, CN, alkyl, aryl, ONRaRb, or NRaC(O)ORb;
• R2 is H and R3 is OH;
• or R2 is OH and R3 is H;
• R4 is OH, alkyl-O—, alkylC(═O)O, alkyl-S—, or alkylC(═O)—S—;
• R5 is OH, alkyl-O—, alkylC(═O)O, alkyl-S—, or alkylC(═O)—S—
• Ra, Rb, Rc, Rd are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl and NO;
• or Ra and Rb together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• or Rb and Rc together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• Re is alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl or NO;
• and Rf is H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl and NO;
• or Re and Rf together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• which ring is optionally substituted with one or more halo, hydroxyl, alkyl, alkenyl, or alkynyl;
• wherein any alkyl, cycloalkyl, alkenyl, alkynyl, or acyl is optionally substituted with 1 to 3 substituents selected from the group consisting of alkoxy, acyl, acylamino, acyloxy, oxyacyl, amino, substituted amino, aminoacyl, aryl, aryloxy, cyano, halogen, hydroxyl, nitro, N3, carboxyl, carboxyl esters, thiol, thioalkyl, thioaryl, thioheteroaryl, thiocycloalkyl, thioheterocyclic, cycloalkyl, heteroaryl, and heterocyclic;
• and wherein any aryl, heteroaryl, or heterocycle is optionally substituted with 1 to 3 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, acyl, acylamino, acyloxy, oxyacyl, amino, substituted amino, aminoacyl, aryl, aryloxy, cyano, halogen, hydroxyl, nitro, N3, carboxyl, carboxyl esters, thiol, thioalkyl, thioaryl, thioheteroaryl, thiocycloalkyl, thioheterocyclic, cycloalkyl, heteroaryl, and heterocyclic.
• or a pharmaceutically acceptable salt or prodrug thereof;
• and a pharmacuetically acceptable carrier;
• which further comprises interferon-α or pegylated interferon-α (peginterferon-α).

A method for treating a viral infection selected from hepatitis B, hepatitis C, Polio, Coxsackie A and B, Rhino, Echo, small pox, Ebola, and West Nile in an animal, comprising administering to the animal an effective amount of a compound that has the formula:

• wherein:
• R is ORa, SRa, NReRf, NRaNRbRc, alkyl, alkenyl, alkynyl, aryl, (CH2)nNRaRb, (CH2)nORa, C(═NRa)NRbRc, (CH2)n—CH(NHRa)CO2Rb, (CH2)n—S-alkyl, (CH2)n—S-aryl, Cl, F, Br, I, CN, COORa, CONRaRb, NHC(═NRa)NHRb, NRaORb, NRaNO, NHCONHRa, NRaN═NRb, NRaN═CHRb, NRaC(O)NRbRc, NRaC(S)NRbRc, NRaC(O)ORb, CH═N—ORa, NRaC(═NH)NRbRc, NRaC(O)NRbNRcRd, O—C(O)Ra, OC(O)—ORa, ONH—C(O)O-alkyl, ONHC(O)O-aryl, ONRaRb, SNRaRb, S—ONRaRb, or SO2NRaRb;
• n is 0, 1, 2, 3, 4, or 5;
• R1 is H, NRaRb, Cl, F, ORa, SRa, NHCORa, NHSO2Ra, NHCONHRa, CN, alkyl, aryl, ONRaRb, or NRaC(O)ORb;
• R2 is H and R3 is OH;
• or R2 is OH and R3 is H;
• R4 is OH, alkyl-O—, alkylC(═O)O, alkyl-S—, or alkylC(═O)—S—;
• R5 is OH, alkyl-O—, alkylC(═O)O, alkyl-S—, or alkylC(═O)—S—
• Ra, Rb, Rc, Rd are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl and NO;
• or Ra and Rb together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• or Rb and Rc together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• Re is alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl or NO;
• and Rf is H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl and NO;
• or Re and Rf together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• which ring is optionally substituted with one or more halo, hydroxyl, alkyl, alkenyl, or alkynyl;
• wherein any alkyl, cycloalkyl, alkenyl, alkynyl, or acyl is optionally substituted with 1 to 3 substituents selected from the group consisting of alkoxy, acyl, acylamino, acyloxy, oxyacyl, amino, substituted amino, aminoacyl, aryl, aryloxy, cyano, halogen, hydroxyl, nitro, N3, carboxyl, carboxyl esters, thiol, thioalkyl, thioaryl, thioheteroaryl, thiocycloalkyl, thioheterocyclic, cycloalkyl, heteroaryl, and heterocyclic;
• and wherein any aryl, heteroaryl, or heterocycle is optionally substituted with 1 to 3 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, acyl, acylamino, acyloxy, oxyacyl, amino, substituted amino, aminoacyl, aryl, aryloxy, cyano, halogen, hydroxyl, nitro, N3, carboxyl, carboxyl esters, thiol, thioalkyl, thioaryl, thioheteroaryl, thiocycloalkyl, thioheterocyclic, cycloalkyl, heteroaryl, and heterocyclic;
• or a pharmaceutically acceptable salt or prodrug thereof.

A method for inhibiting an HCV RNA or DNA polymerase comprising contacting the polymerase in vitro or in vivo with an effective inhibitory amount of a compound of the formula:

• wherein
• R is ORa, SRa, NReRf, NRaNRbRc, alkyl, alkenyl, alkynyl, aryl, (CH2)nNRaRb, (CH2)nORa, C(═NRa)NRbRc, (CH2)n—CH(NHRa)CO2Rb, (CH2)n—S-alkyl, (CH2)n—S-aryl, Cl, F, Br, I, CN, COORa, CONRaRb, NHC(═NRa)NHRb, NRaORb, NRaNO, NHCONHRa, NRaN═NRb, NRaN═CHRb, NRaC(O)NRbRc, NRaC(S)NRbRc, NRaC(O)ORb, CH═N—ORa, NRaC(═NH)NRbRc, NRaC(O)NRbNRcRd, O—C(O)Ra, OC(O)—ORa, ONH—C(O)O-alkyl, ONHC(O)O-aryl, ONRaRb, SNRaRb, S—ONRaRb, or SO2NRaRb;
• n is 0, 1, 2, 3, 4, or 5;
• R1 is H, NRaRb, Cl, F, ORa, SRa, NHCORa, NHSO2Ra, NHCONHRa, CN, alkyl, aryl, ONRaRb, or NRaC(O)ORb;
• R2 is H and R3 is OH;
• or R2 is OH and R3 is H;
• R4 is OH, alkyl-O—, alkylC(═O)O, alkyl-S—, or alkylC(═O)—S—;
• R5 is OH, alkyl-O—, alkylC(═O)O, alkyl-S—, or alkylC(═O)—S—
• Ra, Rb, Rc, Rd are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl and NO;
• or Ra and Rb together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• or Rb and Rc together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• Re is alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl or NO;
• and Rf is H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl and NO;
• or Re and Rf together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• which ring is optionally substituted with one or more halo, hydroxyl, alkyl, alkenyl, or alkynyl;
• wherein any alkyl, cycloalkyl, alkenyl, alkynyl, or acyl is optionally substituted with 1 to 3 substituents selected from the group consisting of alkoxy, acyl, acylamino, acyloxy, oxyacyl, amino, substituted amino, aminoacyl, aryl, aryloxy, cyano, halogen, hydroxyl, nitro, N3, carboxyl, carboxyl esters, thiol, thioalkyl, thioaryl, thioheteroaryl, thiocycloalkyl, thioheterocyclic, cycloalkyl, heteroaryl, and heterocyclic;
• and wherein any aryl, heteroaryl, or heterocycle is optionally substituted with 1 to 3 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, acyl, acylamino, acyloxy, oxyacyl, amino, substituted amino, aminoacyl, aryl, aryloxy, cyano, halogen, hydroxyl, nitro, N3, carboxyl, carboxyl esters, thiol, thioalkyl, thioaryl, thioheteroaryl, thiocycloalkyl, thioheterocyclic, cycloalkyl, heteroaryl, and heterocyclic, or a pharmaceutically acceptable salt or prodrug thereof.

A compound of the formula:

• wherein:
• R is ORa, SRa, NReRf, NRaNRbRc, alkyl, alkenyl, alkynyl, aryl, (CH2)nNRaRb, (CH2)nORa, C(═NRa)NRbRc, (CH2)n—CH(NHRa)CO2Rb, (CH2)n—S-alkyl, (CH2)n—S-aryl, Cl, F, Br, I, CN, COORa, CONRaRb, NHC(═NRa)NHRb, NRaORb, NRaNO, NHCONHRa, NRaN═NRb, NRaN═CHRb, NRaC(O)NRbRc, NRaC(S)NRbRc, NRaC(O)ORb, CH═N—ORa, NRaC(═NH)NRbRc, NRaC(O)NRbNRcRd, O—C(O)Ra, OC(O)—ORa, ONH—C(O)O-alkyl, ONHC(O)O-aryl, ONRaRb, SNRaRb, S—ONRaRb, or SO2NRaRb;
• n is 0, 1, 2, 3, 4, or 5;
• R1 is H, NRaRb, Cl, F, ORa, SRa, NHCORa, NHSO2Ra, NHCONHRa, CN, alkyl, aryl, ONRaRb, or NRaC(O)ORb;
• R2 is H and R3 is OH;
• or R2 is OH and R3 is H;
• R4 is OH, alkyl-O—, alkylC(═O)O, alkyl-S—, or alkylC(═O)—S—;
• R5 is OH, alkyl-O—, alkylC(═O)O, alkyl-S—, or alkylC(═O)—S—
• Ra, Rb, Rc, Rd are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl and NO;
• or Ra and Rb together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• or Rb and Rc together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• Re is alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl or NO;
• and Rf is H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, acyl, SO2-alkyl and NO;
• or Re and Rf together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, azetidino, morpholino, pyrrolino, or thiomorpholino ring;
• which ring is optionally substituted with one or more halo, hydroxyl, alkyl, alkenyl, or alkynyl;
• wherein any alkyl, cycloalkyl, alkenyl, alkynyl, or acyl is optionally substituted with 1 to 3 substituents selected from the group consisting of alkoxy, acyl, acylamino, acyloxy, oxyacyl, amino, substituted amino, aminoacyl, aryl, aryloxy, cyano, halogen, hydroxyl, nitro, N3, carboxyl, carboxyl esters, thiol, thioalkyl, thioaryl, thioheteroaryl, thiocycloalkyl, thioheterocyclic, cycloalkyl, heteroaryl, and heterocyclic;
• and wherein any aryl, heteroaryl, or heterocycle is optionally substituted with 1 to 3 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, acyl, acylamino, acyloxy, oxyacyl, amino, substituted amino, aminoacyl, aryl, aryloxy, cyano, halogen, hydroxyl, nitro, N3, carboxyl, carboxyl esters, thiol, thioalkyl, thioaryl, thioheteroaryl, thiocycloalkyl, thioheterocyclic, cycloalkyl, heteroaryl, and heterocyclic;
• or a pharmaceutically acceptable salt or prodrug thereof.