Nucleoside aryl phosphoramidates for the treatment of RNA-dependent RNA viral infection

A compound of the structural formula I:

• or a pharmaceutically acceptable salts thereof;
• wherein
• n is 0, 1, or 2;
• Ar is phenyl, naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, indolyl, quinolinyl, or isoquinolinyl, wherein Ar is optionally substituted with one to five substituents independently selected from the group consisting of halogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, cyano, nitro, amino, carboxy, trifluoromethyl, trifluoromethoxy, C1-4 alkylamino, di(C1-4 alkyl)amino, C1-4 alkylcarbonyl, C1-4 alkylcarbonyloxy, and C1-4 alkyloxycarbonyl;
• R1 is hydrogen or fluoro;
• R2 is fluoro, methoxy, or OR10;
• R3 is selected from the group consisting of hydrogen, C1-16 alkylcarbonyl, C2-18 alkenylcarbonyl,
• C1-10 alkyloxycarbonyl, C3-6 cycloalkylcarbonyl, C3-6 cycloalkyloxycarbonyl, and an amino acyl residue of structural formula:
• R10 is selected from the group consisting of hydrogen, C1-16 alkylcarbonyl, C2-18 alkenylcarbonyl, C1-10 alkyloxycarbonyl, C3-6 cycloalkylcarbonyl, C3-6 cycloalkyloxycarbonyl, and an amino acyl residue of structural formula:
• or R3 and R10 together with the oxygen atoms to which they are attached form a five-membered cyclic carbonate;
• R4 is hydrogen, C1-5 alkyl, phenyl, or benzyl;
• wherein alkyl is optionally substituted with one substituent selected from the group consisting of fluorine, hydroxy, methoxy, amino, carboxy, carbamoyl, guanidino, mercapto, methylthio, 1H-imidazolyl, and 1H-indol-3-yl;
• and wherein phenyl and benzyl are optionally substituted with one to two substituents independently selected from the group consisting of halogen, hydroxy, and methoxy;
• R5 is hydrogen or methyl;
• or R4 and R5 together with the carbon atom to which they attached form a 3- to 6-membered aliphatic spirocyclic ring system;
• R6 is hydrogen, C1-16 alkyl, C2-20 alkenyl, (CH2)nC3-6 cycloalkyl, phenyl, benzyl, or adamantyl;
• wherein alkyl, alkenyl, cycloalkyl, and adamantyl are optionally substituted with one to three substituents independently selected from halogen, hydroxy, carboxy, C1-4 alkoxy;
• and wherein phenyl and benzyl are optionally substituted with one to three substituents independently selected from halogen, hydroxy, cyano, C1-4 alkoxy, trifluoromethyl, and trifluoromethoxy;
• R7 is hydrogen, C1-5 alkyl, or phenyl C0-2 alkyl;
• R8 is hydrogen, C1-4 alkyl, C1-4 acyl, benzoyl, C1-4 alkyloxycarbonyl, phenyl C0-2 alkyloxycarbonyl, C1-4 alkylaminocarbonyl, phenyl C0-2 alkylaminocarbonyl, C1-4 alkylsulfonyl, or phenyl C0-2 alkylsulfonyl;
• and
• R9 is hydrogen, C1-8 alkylcarbonyl, or C1-8 alkyloxycarbonyl.