Pharmaceutical compositions comprising substituted nucleotide and nucleoside for treating viral infections

A compound of Formula Ir:

• or a pharmaceutically acceptable salt thereof, wherein
• R5 is H or D;
• U is O or S;
• E is CH2 or CD2;
• R1 is one of the formula:
• Y is O or S;
• Y1 is OH or BH3−M+;
• each X is independently O, S, NH, NR8, NHOH, NR8OH, NHOR8, or NR8OR8;
• wherein at least one X is S;
• W is CH, N, or CR8;
• Z is CH, N, or CR8;
• R8 is methyl, trifluoromethyl, fluoro, iodo, alkenyl, alkynyl, vinyl, allyl, halogen, halogentated alkyl, hydroxyl alkyl, acyl, lipid, geranyl, C1-22 alkyl optionally substituted with one or more, the same or different, R10;
• R3, R4, R6, R7 and R14 are each independently selected from H, D, C1-22 alkyl, C2-22 alkenyl, C2-22 alkynyl, allyl, ethynyl, vinyl, C1-22 alkoxy, OH, SH, NH2, N3, CHO, CN, Cl, Br, F, I, or C1-22 alkyl optionally substituted with one or more, the same or different, R10;
• each R10 is independently selected from alkyl, deutero, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, alkanoyl, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl.

A compound having the structure:

• or a pharmaceutically acceptable salt thereof,
• wherein R2 is selected from C1-22 alkyl, C2-22 alkenyl, C2-22 alkynyl, branched alkyl, or cycloalkyl;
• R6 is lipid, C1-22 alkyl, C2-22 alkenyl, C2-22 alkynyl, branched alkyl, pivaloyloxymethyl, cycloalkyl, or has the formula:
• wherein R4 is C1-22 alkoxy, C1-22 alkyl, alkyl, branched alkyl, cycloalkyl, or alkoxy.