Diketo acids on nucleobase scaffolds as inhibitors of Flaviviridae

A pharmaceutical composition for treating a patient infected with HIV for an HCV infection which is also present, comprising a therapeutically effective amount of a compound according to the structure:

• wherein the nucleobase scaffold is independently uracil, xantlline, hypoxanthine, 8-oxopurine or purine;
• R1 and R2 are each independently H, C1-6 alkyl, C1-6 fluoroalkyl, unsubstituted or substituted C5-6 cycloalkyl, C1-6 alkenyl, unsubstituted or substituted phenyl, unsubstituted or substituted benzyl, C2-6 alkyl phenyl which phenyl moiety may be optionally substituted, unsubstituted or substituted heteroaryl, C1-6 alkyl substituted with a heteroaryl group which heteroaryl group is optionally substituted, C1-6 alkyl S(O)R or alkyl (SO2)R where R is alkyl, phenyl or substituted phenyl, C1-6 alkyl CO2Ra where Ra is C1-6 alkyl or H, C1-6 alkyl CORa′ where Ra′ is C1-6 alkyl;
• R3 is selected from H, C1-6 alkyl, halogen, hydroxyl, unsubstituted or substituted benzyl, or unsubstituted or substituted phenylthio;
• R4 is CO2Rc where each Rc is independently from H and C1-6 alkyl,
• and pharmaceutically acceptable salts thereof in combination with an effective amount of a second compound which is an anti-HIV agent in combination with a pharmaceutically acceptable carrier, additive or excipient.

A pharmaceutical composition comprising an effective amount of a compound according to the structure:

• wherein the nucleobase scaffold is independently uracil, xanthine, hypoxanthine, 8-oxopurine or purine;
• R1 and R2 are each independently H, C1-6 alkyl, C1-6 fluoroalkyl, unsubstituted or substituted C5-6 cycloalkyl, C1-6 alkenyl, unsubstituted or substituted phenyl, unsubstituted or substituted benzyl, C2-6 alkyl phenyl which phenyl moiety may be optionally substituted, unsubstituted or substituted heteroaryl, C1-6 alkyl substituted with a heteroaryl group which heteroaryl group is optionally substituted, C1-6 alkyl S(O)R or alkyl (SO2)R where R is alkyl, phenyl or substituted phenyl, C1-6 alkyl CO2Ra where Ra is C1-6 alkyl or H, C1-6 alkyl CORa′ where Ra′ is C1-6 alkyl;
• R3 is selected from H, C1-6 alkyl, halogen, hydroxyl, unsubstituted or substituted benzyl, or unsubstituted or substituted phenylthio;
• R4 is CO2Rc where each Rc is independently from H and C1-6 alkyl,
• and pharmaceutically acceptable salts thereof
• in combination with a therapeutically effective amount of at least one additional compound selected from the group consisting of i) an anti-HIV agent, ii) an anti-infective agent other than an anti-HIV agent and iii) an immunomodulator.

A method of reducing the likelihood of an HCV infection in a patient at risk of said infection, said method comprising administering to said patient an effective amount of a compound according to the structure:

• wherein the nucleobase scaffold is independently uracil, xanthine, hypoxanthine, 8-oxopurine or purine;
• R1 and R2 are each independently H, C1-6 alkyl, C1-6 fluoroalkyl, unsubstituted or substituted C5-6 cycloalkyl, C1-6 alkenyl, unsubstituted or substituted phenyl, unsubstituted or substituted benzyl, C2-6 alkyl phenyl which phenyl moiety may be optionally substituted, unsubstituted or substituted heteroaryl, C1-6 alkyl substituted with a heteroaryl group which heteroaryl group is optionally substituted, C1-6 alkyl S(O)R or alkyl (SO2)R where R is alkyl, phenyl or substituted phenyl, C1-6 alkyl CO2Ra where Ra is C1-6 alkyl or H, C1-6 alkyl CORa′ where Ra′ is C1-6 alkyl;
• R3 is selected from H, C1-6 alkyl, halogen, hydroxyl, unsubstituted or substituted benzyl, or unsubstituted or substituted phenylthio;
• R4 is CO2Rc where each Rc is independently from H and C1-6 alkyl, and pharmaceutically acceptable salts thereof.

A method of inhibiting HCV NS5B polymerase in a subject, said method comprising administering to said subject a therapeutically effective amount of a compound according to the chemical structure:

• wherein the nucleobase scaffold is independently uracil, xanthine, hypoxanthine, 8-oxopurine or purine;
• R1 and R2 are each independently H, C1-6 alkyl, C1-6 fluoroalkyl, unsubstituted or substituted C5-6 cycloalkyl, C1-6 alkenyl, unsubstituted or substituted phenyl, unsubstituted or substituted benzyl, C2-6 alkyl phenyl which phenyl moiety may be optionally substituted, unsubstituted or substituted heteroaryl, C1-6 alkyl substituted with a heteroaryl group which heteroaryl group is optionally substituted, C1-6 alkyl S(O)R or alkyl (SO2)R where R is alkyl, phenyl or substituted phenyl, C1-6 alkyl CO2Ra where Ra is C1-6 alkyl or H, C 16 alkyl CORa′ where Ra′ is C1-6 alkyl;
• R3 is selected from H, C1-6 alkyl, halogen, hydroxyl, unsubstituted or substituted benzyl, or unsubstituted or substituted phenylthio;
• R4 is CO2Rc where each Rc is independently from H and C1-6 alkyl,
• and pharmaceutically acceptable salts thereof.