Nucleotide and nucleoside therapeutic compositions and uses related thereto

1. A compound (β-D or β-L) of the following formula:

or a pharmaceutically acceptable salt thereof, wherein

U is O;

X is CH 2 ;

Q is a pyrimidine with at least one thione, thiol or thioether at the 2 and/or 4-position of said pyrimidine;

R 5 is H;

R 2 , R 3 , R 4 , R 8 and R 9 are each independently H, CH 3 , CD 3 , CF 3 , CF 2 H, CFH 2 , OH, SH, NH 2 , N 3 , CHO, CN, Cl, Br, F or I;

R 1 is one of the formula:

Y is O or S;

Y 1 is OAryl or BH 3 − M + ;

Y 2 is OH or BH 3 − M + ;

Aryl is phenyl, 1-naphthyl, 2-naphthyl, aromatic, heteroaromatic, 4-substituted phenyl, 4-chlorophenyl, or 4-bromophenyl;

R 6 is alkyl, halogen, nitro, cyano, hydroxyl, amino, mercapto, formyl, carboxy, alkanoyl, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl) 2 amino, alkylsulfinyl, alkyl sulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein each R 6 is optionally substituted with one or more, the same or different, R 10 ; and

each R 10 is independently selected from alkyl, deutero, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, alkanoyl, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl) 2 amino, alkylsulfinyl, alkyl sulfonyl, aryl sulfonyl, carbocyclyl, aryl, or heterocyclyl.

2. A compound of one of the following formulae:

or a pharmaceutically acceptable salt thereof wherein,

U is O or S;

R 5 is H or D;

R 1 is one of the formula:

Y is O or S;

Y 1 is OAryl or BH 3 − M +

Y 2 is OH or BH 3 − M +

each X is independently O, S, NH, NR 8 , NHOH, NR 8 OH, NHOR 8 , or NR 8 OR 8 ;

R 2 is OH, SH, NH 2 , OR 8 , SR 8 , NHR 8 , NHOH, NR 8 OH, NHOR 8 , or NR 8 OR 8 ;

wherein in Formula Ig and Ih, one of X is S or R 2 is SR 8 , or both X is S and R 2 is SR 8 ;

wherein in Formula Ii, at least one X is S;

W is CH, N, or CR 8 ;

Z is CH, N, or CR 8 ;

R 3 , R 4 , R 7 , R 9 and R 14 are each independently H, C 1-22 alkyl, C 2-22 alkenyl, C 2-22 alkynyl, allyl, ethynyl, vinyl, C 1-22 alkoxy, OH, SH, NH 2 , N 3 , CHO, CN, Cl, Br, F, I, or C 1-22 alkyl optionally substituted with one or more, the same or different, R 10 ;

each R 10 is independently selected from alkyl, deutero, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, alkanoyl, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl) 2 amino, alkylsulfinyl, alkyl sulfonyl, aryl sulfonyl, carbocyclyl, aryl, or heterocyclyl;

Aryl is phenyl, 1-naphthyl, 2-naphthyl, aromatic, heteroaromatic, 4-substituted phenyl, 4-chlorophenyl, or 4-bromophenyl;

R 8 is methyl, alkenyl, alkynyl, vinyl, allyl, halogen, halogentated alkyl, hydroxyl alkyl, acyl, lipid, geranyl, or C 1-22 alkyl optionally substituted with one or more, the same or different, R 10 ;

R 6 is alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, alkanoyl, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl) 2 amino, alkylsulfinyl, alkyl sulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein each R 6 is optionally substituted with one or more, the same or different, R 10 .

3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein

U is O;

W and Z are CH;

R 5 is H;

R 1 is

wherein Y is O and Y 1 is phenoxy; and

R 6 is alkyl.

4. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 3 , R 4 , R 7 , R 9 and R 14 are each independently H, CH 3 , CD 3 , CF 3 , CF 2 H, CFH 2 , OH, SH, NH 2 , N 3 , CHO, CN, Cl, Br, F or I.

5. The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein one X is O and the other X is S.

6. The compound of claim 5 , or a pharmaceutically acceptable salt thereof, wherein R 6 is iso-propyl.

7. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 5 is H, R 3 is H, R 4 is hydroxyl, R 7 is hyroxyl, R 14 is methyl, R 1 is

Y is O, Y 1 is phenoxy, and R 6 is iso-propyl.

8. A compound having one of the following structures:

9. A liposomal composition comprising a compound of claim 1 , or its pharmaceutically acceptable salt, and a pharmaceutically acceptable carrier.

10. A liposomal composition comprising a compound of claim 2 , or its pharmaceutically acceptable salt, and a pharmaceutically acceptable carrier.

11. A liposomal composition comprising a compound of claim 8 , or its pharmaceutically acceptable salt, and a pharmaceutically acceptable carrier.

12. A pharmaceutical composition comprising a compound of claim 1 , or its pharmaceutically acceptable salt, and a pharmaceutically acceptable carrier.

13. A pharmaceutical composition comprising a compound of claim 2 , or its pharmaceutically acceptable salt, and a pharmaceutically acceptable carrier.

14. A pharmaceutical composition comprising a compound of claim 8 , or its pharmaceutically acceptable salt, and a pharmaceutically acceptable carrier.