Nucleoside analogues and methods of use thereof

A compound of formula:

• wherein:
• A and B are C1-C6 alkyl, mono- to per-halo alkyl or —(CH2)nM, with the proviso that:
• A is different from B,
• when one of A and B is methyl, the other is C1-C6 alkyl, —(CH2)nM, or a mono- to per-halo alkyl other than —CF3, and
• one of A and B is C2-C6 alkyl, the other is C1-C6 alkyl, —(CH2)nM, or a mono- to per-halo alkyl other than C2-C6 fluoroalkyl;
• n is 1 to 3;
• M is —OR2, —SR2, —CN, —C(O)OR3, —OC(O)R4,
• or —NHR15;
• R1 is —H, —C1-C6 alkyl, alkylaryl, or a phosphoryl group of formula (XX):
• R2 is H, C1-C6-alkyl, aryl-C1-C6 alkyl, or a phosphoryl group of formula (XX), each of the alkyl and aryl moieties being unsubstituted or substituted with one or more groups selected from halo, —CN, —C(O)OH, —C(O)R3, —N3, —C1-C6 alkyl, —C(O)OR4, —CF3, —C1-C6 alkyl-N3, —SiF5, and —NHR15;
• R3 is H, C1-C6 alkyl, or aryl-C1-C6 alkyl, each of the alkyl and aryl moieties being unsubstituted or substituted with one or more groups selected from halo, —CN, —C(O)OH, —C(O)OR4, —N3, —C1-C6 alkyl-C(O)OR4, —CF3, —C1-C6 alkyl-N3, and —SiF5;
• R4 is C1-C6 alkyl, aryl, or aryl-C1-C6 alkyl, each of the alkyl and aryl moieties being unsubstituted or substituted with one or more groups selected from halo, —CN, —C(O)OH, —N3, —CF3, —C1-C6 alkyl-N3, —SiF5, and —NHR15;
• R5 is H, C1-C6 alkyl, or arylalkyl;
• R6a is H, methyl, isopropyl, n-propyl, or —CH2—CH2—SMe;
• R6b is H or methyl;
• R7 is H or methyl;
• R8 is H, C1-C6 alkyl, or aryl, the aryl being unsubstituted or substituted with one group selected from C1-C6 alkyl and halo;
• R15 is H, C1-C6 alkyl, —SO2-aryl or aryl, each of the aryl moieties being unsubstituted or substituted with one or more C1-C6 alkyl or halo;
• X is O or S;
• C and D are independently —H, —OH, halo, azido, —CN, —NHR2, or —CF3;
• wherein when one of C and D is OH, the other is —H, —OH, azido, —CN, —NHR2, or —CF3,
• Base is:
• R9 is C1-C6 alkyl, —C(O)—C1-C6 alkyl, —C(O)aryl, aryl, or arylalkyl, wherein each of the alkyl and aryl moieties is unsubstituted or substituted with one or more groups selected from halo, —CF3, —N3, and —SF5;
• R10 represents a lipoate group of formula (XXI):
• R11 are the same of different, and represents F or methyl;
• and
• R12 are the same of different, and represents F or —CF3;
• and
• * denotes the R, S, or R/S configuration,
• with the proviso that the compound comprises:
• one or two phosphoryl groups of formula (XX), the compound being free of a lipoate group of formula (XXI),
• one lipoate group of formula (XXI), the compound being free of a phosphoryl group of formula (XX), or
• one lipoate group of formula (XXI) and only one phosphoryl group of formula (XX), said phosphoryl group being in R1, and
• with the further proviso that when the compound is of formula XIII, the compound comprises one lipoate group of formula (XXI),
• or a pharmaceutically acceptable salt thereof.