Antiviral prodrugs of tenofovir

1. A compound of structural Formula I:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 and R 2 are each independently selected from (a) H, (b) —C 1-4 alkyl, (c) —C 1-4 alkyl substituted with —OH, —SH, —SCH 3 , —NH 2 or —NH—C(═NH)—NH 2 , (d) —CH 2 -phenyl, (e) —CH 2 -phenol, (f) —(CH 2 ) 1-2 —COOH, (g) —(CH 2 ) 1-2 —CONH 2 , (h) —CH 2 -1H-indole, (i) —CH 2 -imidazole, (j) aryl or (k) heteroaryl;

R 3 is selected from:

(a) —C 1-10 alkyl unsubstituted or substituted with one to three substituents independently selected from fluoro, chloro, bromo, —OR 7a , —SH, —NR 9a R 10a , —C 3-6 cycloalkyl or spiro—C 3-6 cycloalkyl,

(b) —CH 2 -phenyl unsubstituted or substituted with one to three substituents independently selected from fluoro, chloro, bromo, —OR 8a , —SH, —NR 9a R 10a or —C 1-3 alkyl,

(c) —C 3-8 cycloalkyl unsubstituted or substituted with one to three substituents independently selected from fluoro, chloro, bromo, —OR 8a , —SH, —NR 9a R 10a or —C 1-3 alkyl,

(d) aryl unsubstituted or substituted with one to three substituents independently selected from fluoro, chloro, bromo, —OR 8a , —SH, —NR 9a R 10a or —C 1-3 alkyl,

(e) —C 1-5 alkyl—X—C 1-5 alkyl wherein X is O, S or NH,

(f) heteroaryl unsubstituted or substituted with one to three substituents independently selected from fluoro chloro, bromo, —OR 8a , —SH, —NR 9a R 10a or —C 1-3 alkyl, or

(g) a heterocyclic ring unsubstituted or substituted with one to three substituents independently selected from fluoro, chloro, bromo, —OR 8a , —SH, —NR 9a R 10a or —C 1-3 alkyl;

R 4 is selected from:

(a) —C 1-10 alkyl unsubstituted or substituted with one to three substituents independently selected from fluoro, chloro, bromo, —OR 7b , —SH, —NR 9b R 10b , —C 3-6 cycloalkyl or spiro—C 3-6 cycloalkyl,

(b) —CH 2 -phenyl unsubstituted or substituted with one to three substituents independently selected from fluoro, chloro, bromo, —OR 8b , —SH, —NR 9b R 10b or —C 1-3 alkyl,

(c) —C 3-8 cycloalkyl unsubstituted or substituted with one to three substituents independently selected from fluoro, chloro, bromo, —OR 8b , —SH, —NR 9b R 10b or —C 1-3 alkyl,

(d) aryl unsubstituted or substituted with one to three substituents independently selected from fluoro, chloro, bromo, —OR 8b , —SH, —NR 9b R 10b or —C 1-3 alkyl,

(e) —C 1-5 alkyl—X—C 1-5 alkyl wherein X is O, S or NH,

(f) heteroaryl unsubstituted or substituted with one to three substituents independently selected from fluoro chloro, bromo, —OR 8b , —SH, —NR 9b R 10b or —C 1-3 alkyl, or

(g) a heterocyclic ring unsubstituted or substituted with one to three substituents independently selected from fluoro, chloro, bromo, —OR 8b , —SH, —NR 9b R 10b or —C 1-3 alkyl;

R 5 and R 6 are each independently selected from (a) —C 1-4 alkyl, (b) —C 1-4 alkyl substituted with —OH, —SH, —SCH 3 , —NH 2 , —NcyC(═NH)—NH 2 , (c) —CH 2 -phenyl, (d) —CH 2 -phenol, (e) —(CH 2 ) 1-2 —COOH, (f) —(CH 2 ) 1-2 —CONH 2 , (g) —CH 2 -1H-indole, (h) —CH 2 -imidazole, (i) aryl or (j) heteroaryl;

or R 5 and R 6 are joined together with the carbon to which they are both attached to form —C 3-6 cycloalkyl or a 4 to 6-membered heterocyclic ring;

R 7a and R 7b are each independently selected from —H or —C 3-6 cycloalkyl;

R 8a and R 8b are each independently selected from —H, —C 1-3 alkyl or —C 3-6 cycloalkyl;

R 9a and R 10a are each independently selected from —H, —C 1-3 alkyl or —C 3-6 cycloalkyl; and

R 9b and R 10b are each independently selected from —H, —C 1-3 alkyl or —C 3-6 cycloalkyl.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein one of R 1 is —H or —C 1-4 alkyl, and R 2 is —H, —C 1-4 alkyl or —CH 2 -phenyl.

3. The compound of claim 2 or a pharmaceutically acceptable salt thereof wherein R 5 and R 6 are independently selected from —C 1-4 alkyl, or R 5 and R 6 are joined together with the carbon to which they are both attached to form —C 3-6 cycloalkyl.

4. The compound of claim 3 or a pharmaceutically acceptable salt thereof wherein R 3 is:

(a) —C 1-8 alkyl, —CH 2 CH 2 OH, —CH 2 CH 2 CH 2 OH, —CH 2 CH 2 SH, —CH 2 CH 2 CH 2 SH, —CH 2 CH 2 NH 2 , —CH 2 CH 2 CH 2 NH 2 ,

(b) —CH 2 -phenyl, unsubstituted or substituted with one to three substituents independently selected from fluoro, chloro, bromo, —OR 8a , —SH, —NR 9a R 10a or —C 1-3 alkyl,

(c) —C 3-6 cycloalkyl, unsubstituted or substituted with one to three substituents independently selected from fluoro, chloro, bromo, —OR 8a , —SH, —NR 9a R 10a or —C 1-3 alkyl,

(d) phenyl or naphthyl, each unsubstituted or substituted with one to three substituents independently selected from fluoro, chloro, bromo, —OR 8a , —SH, —NR 9a R 10a or —C 1-3 alkyl,

(e) —CH 2 CH 2 OCH 3 , —CH 2 CH 2 CH 2 OCH 3 , —CH 2 CH 2 SCH 3 , —CH 2 CH 2 CH 2 SCH 3 , —CH 2 CH 2 NHCH 3 , —CH 2 CH 2 CH 2 NHCH 3 ,

(f) pyridyl, unsubstituted or substituted with one to three substituents independently selected from fluoro chloro, bromo, —OR 8a , —SH, —NR 9a R 10a or —C 1-3 alkyl, or

(g) piperidinyl, pyrrolidinyl, tetrahydrofuranyl, or tetrahydropyranyl, each unsubstituted or substituted with one to three substituents independently selected from fluoro, chloro, bromo, —OR 8a , —SH, —NR 9a R 10a or —C 1-3 alkyl.

5. The compound of claim 4 or a pharmaceutically acceptable salt thereof wherein R 4 is:

(a) —C 1-8 alkyl, —CH 2 CH 2 OH, —CH 2 CH 2 CH 2 OH, —CH 2 CH 2 SH, —CH 2 CH 2 CH 2 SH, —CH 2 CH 2 NH 2 , —CH 2 CH 2 CH 2 NH 2 ,

(b) —CH 2 -phenyl, unsubstituted or substituted with one to three substituents independently selected from fluoro, chloro, bromo, —OR 8b , —SH, —NR 9b R 10b or —C 1-3 alkyl,

(c) —C 3-6 cycloalkyl, unsubstituted or substituted with one to three substituents independently selected from fluoro, chloro, bromo, —OR 8b , —SH, —NR 9b R 10b or —C 1-3 alkyl,

(d) phenyl or naphthyl, each unsubstituted or substituted with one to three substituents independently selected from fluoro, chloro, bromo, —OR 8b , —SH, —NR 9b R 10b or —C 1-3 alkyl,

(e) —CH 2 CH 2 OCH 3 , —CH 2 CH 2 CH 2 OCH 3 , —CH 2 CH 2 SCH 3 , —CH 2 CH 2 CH 2 SCH 3 , —CH 2 CH 2 NHCH 3 , —CH 2 CH 2 CH 2 NHCH 3 ,

(f) pyridyl, unsubstituted or substituted with one to three substituents independently selected from fluoro chloro, bromo, —OR 8b , —SH, —NR 9b R 10b or —C 1-3 alkyl, or

(g) piperidinyl, pyrrolidinyl, tetrahydrofuranyl, or tetrahydropyranyl, each unsubstituted or substituted with one to three substituents independently selected from fluoro, chloro, bromo, —OR 8b , —SH, —NR 9b R 10b or —C 1-3 alkyl.

6. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein R 3 and R 4 are each independently unsubstituted or substituted and each is independently selected from —C 1-8 alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or —CH2-phenyl.

7. The compound of claim 2 or a pharmaceutically acceptable salt thereof wherein R 3 and R 4 are each independently unsubstituted or substituted and each is independently selected from —C 1-8 alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or —CH 2 -phenyl.

8. The compound of claim 3 or a pharmaceutically acceptable salt thereof wherein R 3 and R 4 are each independently unsubstituted or substituted and each is independently selected from —C 1-8 alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or —CH2-phenyl.

9. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein R 3 and R 4 are each unsubstituted and independently selected from —C 2-6 alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or —CH 2 -phenyl.

10. The compound of claim 2 or a pharmaceutically acceptable salt thereof wherein R 3 and R 4 are each unsubstituted and independently selected from —C 2-6 alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or —CH 2 -phenyl.

11. The compound of claim 3 or a pharmaceutically acceptable salt thereof wherein R 3 and R 4 are each unsubstituted and independently selected from —C 2-6 alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or —CH 2 -phenyl.

12. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein:

R 1 is —H or —CH 3;

R 2 is —H, —CH 3 or —CH 2 -phenyl;

R 3 is selected from —C 1-8 alkyl, —C 3-6 cycloalkyl or —CH 2 -phenyl;

R 4 is selected from —C 1-8 alkyl or —C 3-6 cycloalkyl; and

R 5 and R6 are both —CH 3 ;

or R 5 and R 6 are joined together with the carbon to which they are both attached to form —C 3-6 cycloalkyl.

13. The compound of claim 1 that is:

Isopropyl 2-4(S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-y0oxy)methyl)(((S)-1-isopropoxy-1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Isopropyl 2-(((R)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-isopropoxy -1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Pentyl 2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-isopropoxy-1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Pentyl 2-(((R)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-isopropoxy-1-oxopropan-2-ypoxy)phosphoryl)amino)-2-methylpropanoate;

Isopropyl 2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(2-isopropoxy-2-oxoethoxy)phosphoryl)amino)-2-methylpropanoate;

Isopropyl 2-(((R)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(2-isopropoxy-2-oxoethoxy)phosphoryl)amino)-2-methylpropanoate;

Pentyl 2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(2-isopropoxy-2-oxoethoxy)phosphoryl)amino)-2-methylpropanoate;

Pentyl 2-(((R)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(2-isopropoxy-2-oxoethoxy)phosphoryl)amino)-2-methylpropanoate;

Cyclopentyl 2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-(cyclopentyloxy)-1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Cyclopentyl 2-(((R)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-(cyclopentyloxy)-1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Hexyl 2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(2-isopropoxy-2-oxoethoxy)phosphoryl)amino)-2-methylpropanoate;

Hexyl 2-(((R)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(2-isopropoxy-2-oxoethoxy)phosphoryl)amino)-2-methylpropanoate;

Hexyl 2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-isopropoxy-1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Hexyl 2-(((R)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-isopropoxy-1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Isopropyl 2-(((R)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(2-oxo-2-(pentyloxy)ethoxy)phosphoryl)amino)-2-methylpropanoate;

Isopropyl 2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(2-oxo-2-(pentyloxy)ethoxy)phosphoryl)amino)-2-methylpropanoate;

Hexyl 2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(4R)-1-isopropoxy-1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Hexyl 2-(((R)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((R)-1-isopropoxy-1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Isopropyl 2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-oxo-1-(pentyloxy)propan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Isopropyl 2-(((R)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-oxo-1-(pentyloxy)propan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Butyl 2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-(cyclopentyloxy) -1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Butyl 2-(((R)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-(cyclopentyloxy) -1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Cyclohexyl 2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-isopropoxy -1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Cyclohexyl 2-(((R)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-isopropoxy -1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Isopropyl 2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-(cyclopentyloxy)-1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Isopropyl 2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-(cyclopentyloxy)-1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Cyclopentyl 2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(2-isopropoxy-2-oxoethoxy)phosphoryl)amino)-2-methylpropanoate;

Cyclopentyl 2-(((R)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(2-isopropoxy-2-oxoethoxy)phosphoryl)amino)-2-methylpropanoate;

Cyclohexyl 2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(2-isopropoxy-2-oxoethoxy)phosphoryl)amino)-2-methylpropanoate;

Cyclohexyl 2-(((R)-((((R)1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(2-isopropoxy-2-oxoethoxy)phosphoryl)amino)-2-methylpropanoate;

Cyclobutyl 2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-isopropoxy -1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Cyclobutyl 2-(((R)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-isopropoxy -1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Cyclobutyl 2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(2-isopropoxy-2-oxoethoxy)phosphoryl)amino)-2-methylpropanoate;

Cyclobutyl 2-(((R)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(2-isopropoxy-2-oxoethoxy)phosphoryl)amino)-2-methylpropanoate;

Cyclopentyl 2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-isopropoxy-1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Cyclopentyl 2-(((R)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-isopropoxy-1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Pentyl 2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-(cyclopentyloxy)-1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Pentyl 2-(((R)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-(cyclopentyloxy)-1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Isopropyl 2-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl) (((R)-1 -is opr op oxy - 1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Propyl 2-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(2-isopropoxy-2-oxoethoxy)phosphoryl)amino)-2-methylpropanoate;

Propyl 2-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-isopropoxy-1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Propyl 2-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((R)-1-i sopropoxy-1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Butyl 2-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(2-isopropoxy-2-oxoethoxy)phosphoryl)amino)-2-methylpropanoate;

Butyl 2-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-isopropoxy-1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Butyl 2-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((R)-1 -isopropoxy-1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Ethyl 2-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(2-isopropoxy-2-oxoethoxy)phosphoryl)amino)-2-methylpropanoate;

Ethyl 2-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-isopropoxy-1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Ethyl 2-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((R)-1-i sopropoxy-1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Isobutyl 2-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-ypoxy)methyl)(2-isopropoxy-2-oxoethoxy)phosphoryl)amino)-2-methylpropanoate;

Isobutyl 2-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-isopropoxy-1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Isopropyl 2-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-isopropoxy-1-oxo-3-phenylpropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Hexyl 2-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-isopropoxy-1-oxo-3-phenylpropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Hexyl 2-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-(cyclopentyloxy)-1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Hexyl 2-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(2-(cyclopentyloxy)-2-oxoethoxy)phosphoryl)amino)-2-methylpropanoate;

Pentyl 2-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(2-(cyclopentyloxy)-2-oxoethoxy)phosphoryl)amino)-2-methylpropanoate;

Isobutyl 2-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-(cyclopentyloxy) -1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Propyl 2-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(2-(cyclopentyloxy)-2-oxoethoxy)phosphoryl)amino)-2-methylpropanoate;

Cyclopentyl 2-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-isopropoxy-1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Isopropyl 2-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-ethoxy-1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Benzyl 2-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-isopropoxy-1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Benzyl 2-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(2-isopropoxy-2-oxoethoxy)phosphoryl)amino)-2-methylpropanoate;

Hexyl 2-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-ethoxy-1-oxopropan -2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Hexyl 2-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)((1-isopropoxy-2-methyl-1-oxopropan-2-yl)oxy)phosphoryl)amino)-2-methylpropanoate;

Isopropyl 1-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(2-isopropoxy-2-oxoethoxy)phosphoryl)amino)cyclopentane-1-carboxylate;

Isopropyl 1-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(2-isopropoxy-2-oxoethoxy)phosphoryl)amino)cyclopropane-1-carboxylate;

Isopropyl 1-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-isopropoxy-1-oxopropan-2-yl)oxy)phosphoryl)amino)cyclopropane-1 -carboxylate;

Isopropyl 1-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-isopropoxy-1-oxopropan-2-yl)oxy)phosphoryl)amino)cyclopentane-1-carboxylate;

Isopropyl 1-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(2-isopropoxy-2-oxoethoxy)phosphoryl)amino)cyclobutane-1-carboxylate;

Isopropyl 1-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-isopropoxy-1-oxopropan-2-yl)oxy)phosphoryl)amino)cyclobutane-l-carboxylate;

Isopropyl 1-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(2-isopropoxy-2-oxoethoxy)phosphoryl)amino)cyclohexane-1-carboxylate; or

Isopropyl 1-((((((R) -1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((S)-1-isopropoxy-1-oxopropan-2-yl)oxy)phosphoryl)amino)cyclohexane-1-carboxylate;

or a pharmaceutically acceptable salt thereof.

14. A pharmaceutical composition comprising an effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

15. The pharmaceutical composition of claim 14 further comprising an effective amount of one or more additional HIV antiviral agent selected from HIV protease inhibitors, HIV integrase inhibitors, non-nucleoside HIV reverse transcriptase inhibitors, nucleoside HIV reverse transcriptase inhibitors, HIV fusion inhibitors and HIV entry inhibitors.

16. A method for the prophylaxis or treatment of infection by HIV or for the prophylaxis, treatment, or delay in the onset of AIDS in a subject in need thereof which comprises administering to the subject an effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof.

17. The method of claim 16 further comprising administering to the subject an effective amount of one or more additional HIV antiviral agent selected from HIV protease inhibitors, HIV integrase inhibitors, non-nucleoside HIV reverse transcriptase inhibitors, nucleoside HIV reverse transcriptase inhibitors, HIV fusion inhibitors and HIV entry inhibitors.

18. The pharmaceutical composition of claim 14 further comprising an effective amount of one or more additional HIV antiviral agent selected from:

abacavir,

abacavir + lamivudine,

abacavir + lamivudine + zidovudine,

amprenavir,

atazanavir,

AZT,

capravirine,

darunavir,

ddC,

ddI,

ddI (enteric coated),

delavirdine,

dolutegravir,

doravirine,

efavirenz,

efavirenz + emtricitabine + tenofovir DF,

4′-ethynyl-2-fluoro-2′-deoxyadenosine,

elvitegravir,

emtricitabine,

emtricitabine + tenofovir DF,

emivirine,

enfuvirtide,

enteric coated didanosine,

etravirine,

fosamprenavir calcium,

indinavir,

lamivudine,

lamivudine + zidovudine,

lopinavir,

lopinavir + ritonavir,

maraviroc,

nelfinavir,

nevirapine,

PPL-100,

raltegravir,

rilpivirine

ritonavir,

saquinavir,

stavudine,

tipranavir, or

vicriviroc.