Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase of hepatitis C virus

A compound of the structural formula:

• or a pharmaceutically aceptable salt thereof;
• wherein Ra and Rh are each independently selected from the group consisting of hydrogen, cyano, azido, halogen, hydroxy, mercapto, amino, C1-4 alkoxy, C2-4 alkenyl, C2-4 alkynyl, and C1-4 alkyl, wherein alkyl is unsubstituted or substituted with hydroxy, amino, C1-4 alkoxy, C1-4 alkylthio, or one to three fluorine atoms;
• Rb is C2-4 alkenyl, C2-4 alkynyl, or C1-4 alkyl, wherein alkyl is unsubstituted or substituted with hydroxy, amino, C1-4 alkoxy, C1-4 alkylthio, or one to three fluorine atoms;
• Rc is hydrogen, fluorine, hydroxy, mercapto, C1-4 alkoxy, or C1-4 alkyl;
• or Rb and Rc together with the carbon atom to which they are attached form a 3- to 6-membered saturated monocyclic ring system optionally containing a heteroatom selected from O, S, and NC0-4 alkyl;
• Rd is hydrogen, cyano, nitro, C1-3 alkyl, NHCONH2, CONRjRj, CSNRjRj, COORj, C(═NH)NH2, hydroxy, C1-3 alkoxy, amino, C1-4 alkylamino, di(C1-4 alkyl)amino, halogen, (1,3-oxazol-2-yl), (1,3-thiazol-2-yl), or (imidazol-2-yl);
• wherein alkyl is unsubstituted or substituted with one to three groups independently selected from halogen, amino, hydroxy, carboxy, and C1-3 alkoxy;
• Re and Rf are each independently hydrogen, hydroxy, halogen, C1-4 alkoxy, amino, C1-4 alkylamino, di(C1-4 alkyl)amino, C3-6 cycloalkylamino, di(C3-6 cycloalkyl)amino, or C4-6 cycloheteroalkyl, unsubstituted or substituted with one to two groups independently selected from halogen, hydroxy, amino, C1-4 alkyl, and C1-4 alkoxy;
• Rg is hydrogen, C1-4 alkyl, C2-4 alkynyl, halogen, cyano, carboxy, C1-4 alkyloxycarbonyl, azido, amino, C1-4 alkylamino, di(C1-4 alkyl)amino, hydroxy, C1-6 alkoxy, C1-6 alkylthio, C1-6 alkylsulfonyl, (C1-4 alkyl)0-2 aminomethyl, or C4-6 cycloheteroalkyl, unsubstituted or substituted with one to two groups independently selected from halogen, hydroxy, amino, C1-4 alkyl, and C1-4 alkoxy;
• Ri is hydrogen, C1-10 alkylcarbonyl, P3O9H4, P2O6H3, or P(O)RmRn;
• each Rj is independently hydrogen or C1-6 alkyl;
• Rk and Rl are each independently hydrogen, methyl, hydroxymethyl, or fluoromethyl;
• and
• Rm and Rn are each independently hydroxy, OCH2CH2SC(═O)C1-4 alkyl, OCH2O(C═O)OC1-4 alkyl, NHCHMeCO2Me, OCH(C1-4 alkyl)O(C═O)C1-4 alkyl,
• with the provisos that (a) when Ra and Rc are α-hydroxy, Re is amino, Rb is β-methyl, Rh is hydrogen, and Rf, Rg, Ri, Rk, and Rl are hydrogen, then Rd is not cyano or CONH2 and (b) when Ra and Rc are α-hydroxy, Re is amino, Rh is β-methyl, Rb is hydrogen, and Rf, Rg, Ri, Rk, and Rl are hydrogen, then Rd is not cyano or CONH2.