Antiviral beta-amino acid ester phosphodiamide compounds

1. A compound of structural Formula I:

or pharmaceutically acceptable salt thereof, wherein:

R 1 and R 2 are each independently H or —C 1-4 alkyl;

R 3 is —C 1-10 alkyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl;

R A is an L-amino acid ester residue of formula (i), a D-amino acid ester residue of formula (ii), or a geminally di-substituted amino acid ester residue of formula (iv):

R 4 is (a) —C 1-4 alkyl, (b) —C 1-4 alkyl substituted with —OH, —SH, —SCH 3 , —NH 2 , —NH—C(═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;

R 5 and R 6 are each CH 3 ; and

R 9 is —C 1-10 alkyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

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

3. The compound of claim 2 or a pharmaceutically acceptable salt thereof wherein R 3 is —C 3-8 alkyl.

4. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R A is:

R 4 is —C 1-4 alkyl; and

R9 is —C 1-8 alkyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

5. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R A is:

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

R 1 is H or —C 1-4 alkyl;

R 2 is H or —C 1-4 alkyl,

R 3 is —C 1-8 alkyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl;

R 4 is —CH 3 ;

R 5 and R 6 are both —CH 3 ;

and

R 9 is —C 1-8 alkyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

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

one of R 1 and R 2 is H, and the other is methyl or i-propyl;

R 3 is i-propyl;

R 4 is —CH 3 ;

and

R 9 is —C 3-8 alkyl, cyclobutyl, cyclopentyl or cyclohexyl.

8. The compound of claim 1 that is:

1-methylethyl N—[(S)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(2S)-2-methyl-3-(1-methylethoxy)-3-oxopropyl]amino}phosphoryl]-L-alaninate;

1-methylethyl N—[(R)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(2S)-2-methyl-3-(1-methylethoxy)-3-oxopropyl]amino}phosphoryl]-L-alaninate;

1-methylethyl N—[(S)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[3-(1-methylethoxy)-3-oxopropyl]amino}phosphoryl]-L-alaninate;

1-methylethyl N—[(R)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[3-(1-methylethoxy)-3-oxopropyl]amino}phosphoryl]-L-alaninate;

1-methylethyl (3S)-3-{[(R)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(1S)-1-methyl-2-(1-methylethoxy)-2-oxoethyl]amino}phosphoryl]amino}butanoate;

1-methylethyl (3S)-3-{[(S)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(1S)-1-methyl-2-(1-methylethoxy)-2-oxoethyl]amino}phosphoryl]amino}butanoate;

1-methylethyl (3R)-3-{[(S)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(1S)-1-methyl-2-(1-methylethoxy)-2-oxoethyl]amino}phosphoryl]amino}butanoate;

1-methylethyl (3R)-3-{[(R)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(1S)-1-methyl-2-(1-methylethoxy)-2-oxoethyl]amino}phosphoryl]amino}butanoate;

1-methylethyl N—[(S)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(2R)-2-methyl-3-(1-methylethoxy)-3-oxopropyl]amino}phosphoryl]-L-alaninate;

1-methylethyl N—[(R)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(2R)-2-methyl-3-(1-methylethoxy)-3-oxopropyl]amino}phosphoryl]-L-alaninate;

cyclopentyl N—[(S)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(2S)-2-methyl-3-(1-methylethoxy)-3-oxopropyl]amino}phosphoryl]-L-alaninate;

cyclopentyl N—[(R)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(2S)-2-methyl-3-(1-methylethoxy)-3-oxopropyl]amino}phosphoryl]-L-alaninate;

cyclobutyl N—[(S)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(2S)-2-methyl-3-(1-methylethoxy)-3-oxopropyl]amino}phosphoryl]-L-alaninate;

cyclobutyl N—[(R)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(2S)-2-methyl-3-(1-methylethoxy)-3-oxopropyl]amino}phosphoryl]-L-alaninate;

cyclohexyl N—[(S)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(2S)-2-methyl-3-(1-methylethoxy)-3-oxopropyl]amino}phosphoryl]-L-alaninate;

cyclohexyl N—[(R)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(2S)-2-methyl-3-(1-methylethoxy)-3-oxopropyl]amino}phosphoryl]-L-alaninate;

2-methylpropyl N—[(S)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(2S)-2-methyl-3-(1-methylethoxy)-3-oxopropyl]amino}phosphoryl]-L-alaninate;

2-methylpropyl N—[(R)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(2S)-2-methyl-3-(1-methylethoxy)-3-oxopropyl]amino}phosphoryl]-L-alaninate;

butyl N—[(S)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(2S)-2-methyl-3-(1-methylethoxy)-3-oxopropyl]amino}phosphoryl]-L-alaninate;

butyl N—[(R)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(2S)-2-methyl-3-(1-methylethoxy)-3-oxopropyl]amino}phosphoryl]-L-alaninate;

pentyl N—[(S)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(2S)-2-methyl-3-methylethoxy)-3-oxopropyl]amino}phosphoryl]-L-alaninate;

pentyl N—[(R)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(2S)-2-methyl-3-(1-methylethoxy)-3-oxopropyl]amino}phosphoryl]-L-alaninate;

heptyl N—[(S)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(2S)-2-methyl-3-methylethoxy)-3-oxopropyl]amino}phosphoryl]-L-alaninate;

heptyl N—[(R)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(2S)-2-methyl-3-(1-methylethoxy)-3-oxopropyl]amino}phosphoryl]-L-alaninate;

isopropyl (3R)-3-(((S)—((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((R)-1-cyclobutoxy-1-oxopropan-2-yl)amino)phosphoryl)amino)butanoate;

isopropyl (3R)-3-(((R)—((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(((R)-1-cyclobutoxy-1-oxopropan-2-yl)amino)phosphoryl)amino)butanoate;

1-methylethyl (3S)-3-{[(S)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(1R)-2-(cyclobutyloxy)-1-methyl-2-oxoethyl]amino}phosphoryl]amino}butanoate;

1-methylethyl (3S)-3-{[(R)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(1R)-2-(cyclobutyloxy)-1-methyl-2-oxoethyl]amino}phosphoryl]amino}butanoate;

cyclobutyl N—[(S)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(2S)-2-methyl-3-(1-methylethoxy)-3-oxopropyl]amino}phosphoryl]-D-alaninate;

cyclobutyl N—[(R)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(2S)-2-methyl-3-(1-methylethoxy)-3-oxopropyl]amino}phosphoryl]-D-alaninate;

cyclohexyl N—[(S)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(2S)-2-methyl-3-(1-methylethoxy)-3-oxopropyl]amino}phosphoryl]-D-alaninate;

cyclohexyl N—[(R)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(2S)-2-methyl-3-(1-methylethoxy)-3-oxopropyl]amino}phosphoryl]-D-alaninate;

cyclopentyl N—[(S)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(2S)-2-methyl-3-(1-methylethoxy)-3-oxopropyl]amino}phosphoryl]-D-alaninate;

cyclopentyl N—[(R)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[(2S)-2-methyl-3-(1-methylethoxy)-3-oxopropyl]amino}phosphoryl]-D-alaninate;

cyclobutyl N—[(S)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[3-(1-methylethoxy)-3-oxopropyl]amino}phosphoryl]-D-alaninate;

cyclobutyl N—[(R)-{[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}{[3-(1-methylethoxy)-3-oxopropyl]amino}phosphoryl]-D-alaninate;

isopropyl (3S)-3-(((S)—((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)((2-methyl-1-oxo-1-(pentyloxy)propan-2-yl)amino)phosphoryl)amino)-4-methylpentanoate;

isopropyl (3S)-3-(((R)—((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)((2-methyl-1-oxo-1-(pentyloxy)propan-2-yl)amino)phosphoryl)amino)-4-methylpentanoate;

isopropyl (3S)-3-(((S)—((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)((1-isopropoxy-2-methyl-1-oxopropan-2-yl)amino)phosphoryl)amino)-4-methylpentanoate;

isopropyl (3S)-3-(((R)—((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)((1-isopropoxy-2-methyl-1-oxopropan-2-yl)amino)phosphoryl)amino)-4-methylpentanoate;

isopropyl (3 S)-3-(((S)—((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)((2-methyl-1-oxo-1-(pentyloxy)propan-2-yl)amino)phosphoryl)amino)-butanoate;

isopropyl (3S)-3-(((R)—((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)((2-methyl-1-oxo-1-(pentyloxy)propan-2-yl)amino)phosphoryl)amino)-butanoate;

isopropyl (3R)-3-(((S)—((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)((2-methyl-1-oxo-1-(pentyloxy)propan-2-yl)amino)phosphoryl)amino)-butanoate;

isopropyl (3R)-3-(((R)—((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)((2-methyl-1-oxo-1-(pentyloxy)propan-2-yl)amino)phosphoryl)amino)-butanoate;

isopropyl (3 S)-3-(((S)—((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)((1-(hexyloxy)-2-methyl-1-oxopropan-2-yl)amino)phosphoryl)amino)-4-methylpentanoate; or

isopropyl (3S)-3-(((R)—((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)((1-(hexyloxy)-2-methyl-1-oxopropan-2-yl)amino)phosphoryl)amino)-4-methylpentanoate;

or a pharmaceutically acceptable salt thereof.

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

10. The pharmaceutical composition of claim 9 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.

11. A method for the treatment of infection by HIV or for the 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.

12. The method of claim 11 wherein the subject is human.

13. The method of claim 12 further comprising administering to the human 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.

14. The pharmaceutical composition of claim 9 further comprising an effective amount of one or more additional HIV antiviral agent or agents selected from: abacavir, abacavir sulfate, abacavir+lamivudine, abacavir+lamivudine+zidovudine, amprenavir, atazanavir, atazanavir sulfate, AZT, capravirine, darunavir, ddC, ddI, delavirdine, delavirdine mesylate, dolutegravir, doravirine, efavirenz, efavirenz+emtricitabine+tenofovir DF, 4′-ethynyl-2-fluoro-2′-deoxyadenosine, elvitegravir, emtricitabine, emtricitabine+tenofovir DF, emvirine, enfuvirtide, enteric coated didanosine, etravirine, fosamprenavir calcium, indinavir, indinavir sulfate, lamivudine, lamivudine+zidovudine, lopinavir, lopinavir+ritonavir, maraviroc, nelfinavir, nelfinavir mesylate, nevirapine, PPL-100, raltegravir, rilpivirine, ritonavir, saquinavir, saquinavir mesylate, stavudine, tipranavir and vicriviroc.

15. The compound

16. A pharmaceutical composition comprising an effective amount of the compound of claim 15 and a pharmaceutically acceptable carrier.

17. The pharmaceutical composition of claim 16 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.

18. The pharmaceutical composition of claim 17 comprising an effective amount of one or more additional HIV antiviral agent selected from: abacavir, abacavir sulfate, abacavir+lamivudine, abacavir+lamivudine+zidovudine, amprenavir, atazanavir, atazanavir sulfate, AZT, capravirine, darunavir, ddC, ddI, delavirdine, delavirdine mesylate, dolutegravir, doravirine, efavirenz, efavirenz+emtricitabine+tenofovir DF, 4′-ethynyl-2-fluoro-2′-deoxyadenosine, elvitegravir, emtricitabine, emtricitabine+tenofovir DF, emvirine, enfuvirtide, enteric coated didanosine, etravirine, fosamprenavir calcium, indinavir, indinavir sulfate, lamivudine, lamivudine+zidovudine, lopinavir, lopinavir+ritonavir, maraviroc, nelfinavir, nelfinavir mesylate, nevirapine, PPL-100, raltegravir, rilpivirine, ritonavir, saquinavir, saquinavir mesylate, stavudine, tipranavir and vicriviroc.

19. A method for the treatment of infection by HIV or for the 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 15 .

20. The method of claim 19 wherein the subject is human.

21. The method of claim 20 further comprising administering to the human 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.

22. The method of claim 21 comprising an effective amount of one or more additional HIV antiviral agent selected from: abacavir, abacavir sulfate, abacavir+lamivudine, abacavir+lamivudine+zidovudine, amprenavir, atazanavir, atazanavir sulfate, AZT, capravirine, darunavir, ddC, ddI, delavirdine, delavirdine mesylate, dolutegravir, doravirine, efavirenz, efavirenz+emtricitabine+tenofovir DF, 4′-ethynyl-2-fluoro-2′-deoxyadenosine, elvitegravir, emtricitabine, emtricitabine+tenofovir DF, emvirine, enfuvirtide, enteric coated didanosine, etravirine, fosamprenavir calcium, indinavir, indinavir sulfate, lamivudine, lamivudine+zidovudine, lopinavir, lopinavir+ritonavir, maraviroc, nelfinavir, nelfinavir mesylate, nevirapine, PPL-100, raltegravir, rilpivirine, ritonavir, saquinavir, saquinavir mesylate, stavudine, tipranavir and vicriviroc.

23. A compound that is a pharmaceutically acceptable salt of

24. A pharmaceutical composition comprising an effective amount of the compound of claim 23 and a pharmaceutically acceptable carrier.

25. The pharmaceutical composition of claim 24 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.

26. The pharmaceutical composition of claim 25 comprising an effective amount of one or more additional HIV antiviral agent selected from: abacavir, abacavir sulfate, abacavir+lamivudine, abacavir+lamivudine+zidovudine, amprenavir, atazanavir, atazanavir sulfate, AZT, capravirine, darunavir, ddC, ddI, delavirdine, delavirdine mesylate, dolutegravir, doravirine, efavirenz, efavirenz+emtricitabine+tenofovir DF, 4′-ethynyl-2-fluoro-2′-deoxyadenosine, elvitegravir, emtricitabine, emtricitabine+tenofovir DF, emvirine, enfuvirtide, enteric coated didanosine, etravirine, fosamprenavir calcium, indinavir, indinavir sulfate, lamivudine, lamivudine+zidovudine, lopinavir, lopinavir+ritonavir, maraviroc, nelfinavir, nelfinavir mesylate, nevirapine, PPL-100, raltegravir, rilpivirine, ritonavir, saquinavir, saquinavir mesylate, stavudine, tipranavir and vicriviroc.

27. A method for the treatment of infection by HIV or for the 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 23 .

28. The method of claim 27 wherein the subject is human.

29. The method of claim 28 further comprising administering to the human 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.

30. The method of claim 29 comprising an effective amount of one or more additional HIV antiviral agent selected from: abacavir, abacavir sulfate, abacavir+lamivudine, abacavir+lamivudine+zidovudine, amprenavir, atazanavir, atazanavir sulfate, AZT, capravirine, darunavir, ddC, ddI, delavirdine, delavirdine mesylate, dolutegravir, doravirine, efavirenz, efavirenz+emtricitabine+tenofovir DF, 4′-ethynyl-2-fluoro-2′-deoxyadenosine, elvitegravir, emtricitabine, emtricitabine+tenofovir DF, emvirine, enfuvirtide, enteric coated didanosine, etravirine, fosamprenavir calcium, indinavir, indinavir sulfate, lamivudine, lamivudine+zidovudine, lopinavir, lopinavir+ritonavir, maraviroc, nelfinavir, nelfinavir mesylate, nevirapine, PPL-100, raltegravir, rilpivirine, ritonavir, saquinavir, saquinavir mesylate, stavudine, tipranavir and vicriviroc.

31. The compound

32. A pharmaceutical composition comprising an effective amount of the compound of claim 31 and a pharmaceutically acceptable carrier.

33. The pharmaceutical composition of claim 32 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.

34. The pharmaceutical composition of claim 33 comprising an effective amount of one or more additional HIV antiviral agent selected from: abacavir, abacavir sulfate, abacavir+lamivudine, abacavir+lamivudine+zidovudine, amprenavir, atazanavir, atazanavir sulfate, AZT, capravirine, darunavir, ddC, ddI, delavirdine, delavirdine mesylate, dolutegravir, doravirine, efavirenz, efavirenz+emtricitabine+tenofovir DF, 4′-ethynyl-2-fluoro-2′-deoxyadenosine, elvitegravir, emtricitabine, emtricitabine+tenofovir DF, emvirine, enfuvirtide, enteric coated didanosine, etravirine, fosamprenavir calcium, indinavir, indinavir sulfate, lamivudine, lamivudine+zidovudine, lopinavir, lopinavir+ritonavir, maraviroc, nelfinavir, nelfinavir mesylate, nevirapine, PPL-100, raltegravir, rilpivirine, ritonavir, saquinavir, saquinavir mesylate, stavudine, tipranavir and vicriviroc.

35. A method for the treatment of infection by HIV or for the 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 31 .

36. The method of claim 35 wherein the subject is human.

37. The method of claim 36 further comprising administering to the human 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.

38. The method of claim 37 comprising an effective amount of one or more additional HIV antiviral agent selected from: abacavir, abacavir sulfate, abacavir+lamivudine, abacavir+lamivudine+zidovudine, amprenavir, atazanavir, atazanavir sulfate, AZT, capravirine, darunavir, ddC, ddI, delavirdine, delavirdine mesylate, dolutegravir, doravirine, efavirenz, efavirenz+emtricitabine+tenofovir DF, 4′-ethynyl-2-fluoro-2′-deoxyadenosine, elvitegravir, emtricitabine, emtricitabine+tenofovir DF, emvirine, enfuvirtide, enteric coated didanosine, etravirine, fosamprenavir calcium, indinavir, indinavir sulfate, lamivudine, lamivudine+zidovudine, lopinavir, lopinavir+ritonavir, maraviroc, nelfinavir, nelfinavir mesylate, nevirapine, PPL-100, raltegravir, rilpivirine, ritonavir, saquinavir, saquinavir mesylate, stavudine, tipranavir and vicriviroc.

39. A compound that is a pharmaceutically acceptable salt of

40. A pharmaceutical composition comprising an effective amount of the compound of claim 39 and a pharmaceutically acceptable carrier.

41. The pharmaceutical composition of claim 40 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.

42. The pharmaceutical composition of claim 41 comprising an effective amount of one or more additional HIV antiviral agent selected from: abacavir, abacavir sulfate, abacavir+lamivudine, abacavir+lamivudine+zidovudine, amprenavir, atazanavir, atazanavir sulfate, AZT, capravirine, darunavir, ddC, ddI, delavirdine, delavirdine mesylate, dolutegravir, doravirine, efavirenz, efavirenz+emtricitabine+tenofovir DF, 4′-ethynyl-2-fluoro-2′-deoxyadenosine, elvitegravir, emtricitabine, emtricitabine+tenofovir DF, emvirine, enfuvirtide, enteric coated didanosine, etravirine, fosamprenavir calcium, indinavir, indinavir sulfate, lamivudine, lamivudine+zidovudine, lopinavir, lopinavir+ritonavir, maraviroc, nelfinavir, nelfinavir mesylate, nevirapine, PPL-100, raltegravir, rilpivirine, ritonavir, saquinavir, saquinavir mesylate, stavudine, tipranavir and vicriviroc.

43. A method for the treatment of infection by HIV or for the 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 39 .

44. The method of claim 43 wherein the subject is human.

45. The method of claim 44 further comprising administering to the human 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.

46. The method of claim 45 comprising an effective amount of one or more additional HIV antiviral agent selected from: abacavir, abacavir sulfate, abacavir+lamivudine, abacavir+lamivudine+zidovudine, amprenavir, atazanavir, atazanavir sulfate, AZT, capravirine, darunavir, ddC, ddI, delavirdine, delavirdine mesylate, dolutegravir, doravirine, efavirenz, efavirenz+emtricitabine+tenofovir DF, 4′-ethynyl-2-fluoro-2′-deoxyadenosine, elvitegravir, emtricitabine, emtricitabine+tenofovir DF, emvirine, enfuvirtide, enteric coated didanosine, etravirine, fosamprenavir calcium, indinavir, indinavir sulfate, lamivudine, lamivudine+zidovudine, lopinavir, lopinavir+ritonavir, maraviroc, nelfinavir, nelfinavir mesylate, nevirapine, PPL-100, raltegravir, rilpivirine, ritonavir, saquinavir, saquinavir mesylate, stavudine, tipranavir and vicriviroc.

47. The compound

48. A pharmaceutical composition comprising an effective amount of the compound of claim 47 and a pharmaceutically acceptable carrier.

49. The pharmaceutical composition of claim 48 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.

50. The pharmaceutical composition of claim 49 comprising an effective amount of one or more additional HIV antiviral agent selected from: abacavir, abacavir sulfate, abacavir+lamivudine, abacavir+lamivudine+zidovudine, amprenavir, atazanavir, atazanavir sulfate, AZT, capravirine, darunavir, ddC, ddI, delavirdine, delavirdine mesylate, dolutegravir, doravirine, efavirenz, efavirenz+emtricitabine+tenofovir DF, 4′-ethynyl-2-fluoro-2′-deoxyadenosine, elvitegravir, emtricitabine, emtricitabine+tenofovir DF, emvirine, enfuvirtide, enteric coated didanosine, etravirine, fosamprenavir calcium, indinavir, indinavir sulfate, lamivudine, lamivudine+zidovudine, lopinavir, lopinavir+ritonavir, maraviroc, nelfinavir, nelfinavir mesylate, nevirapine, PPL-100, raltegravir, rilpivirine, ritonavir, saquinavir, saquinavir mesylate, stavudine, tipranavir and vicriviroc.

51. A method for the treatment of infection by HIV or for the 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 47 .

52. The method of claim 51 wherein the subject is human.

53. The method of claim 52 further comprising administering to the human 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.

54. The method of claim 53 comprising an effective amount of one or more additional HIV antiviral agent selected from: abacavir, abacavir sulfate, abacavir+lamivudine, abacavir+lamivudine+zidovudine, amprenavir, atazanavir, atazanavir sulfate, AZT, capravirine, darunavir, ddC, ddI, delavirdine, delavirdine mesylate, dolutegravir, doravirine, efavirenz, efavirenz+emtricitabine+tenofovir DF, 4′-ethynyl-2-fluoro-2′-deoxyadenosine, elvitegravir, emtricitabine, emtricitabine+tenofovir DF, emvirine, enfuvirtide, enteric coated didanosine, etravirine, fosamprenavir calcium, indinavir, indinavir sulfate, lamivudine, lamivudine+zidovudine, lopinavir, lopinavir+ritonavir, maraviroc, nelfinavir, nelfinavir mesylate, nevirapine, PPL-100, raltegravir, rilpivirine, ritonavir, saquinavir, saquinavir mesylate, stavudine, tipranavir and vicriviroc.

55. A compound that is a pharmaceutically acceptable salt of

56. A pharmaceutical composition comprising an effective amount of the compound of claim 55 and a pharmaceutically acceptable carrier.

57. The pharmaceutical composition of claim 56 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.

58. The pharmaceutical composition of claim 57 comprising an effective amount of one or more additional HIV antiviral agent selected from: abacavir, abacavir sulfate, abacavir+lamivudine, abacavir+lamivudine+zidovudine, amprenavir, atazanavir, atazanavir sulfate, AZT, capravirine, darunavir, ddC, ddI, delavirdine, delavirdine mesylate, dolutegravir, doravirine, efavirenz, efavirenz+emtricitabine tenofovir DF, 4′-ethynyl-2-fluoro-2′-deoxyadenosine, elvitegravir, emtricitabine, emtricitabine+tenofovir DF, emvirine, enfuvirtide, enteric coated didanosine, etravirine, fosamprenavir calcium indinavir, indinavir sulfate, lamivudine, lamivudine+zidovudine, lopinavir, lopinavir+ritonavir, maraviroc, nelfinavir, nelfinavir mesylate, nevirapine, PPL-100, raltegravir, rilpivirine, ritonavir, saquinavir, saquinavir mesylate, stavudine, tipranavir and vicriviroc.

59. A method for the treatment of infection by HIV or for the 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 55 .

60. The method of claim 59 wherein the subject is human.

61. The method of claim 60 further comprising administering to the human 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.

62. The method of claim 61 comprising an effective amount of one or more additional HIV antiviral agent selected from: abacavir, abacavir sulfate, abacavir+lamivudine, abacavir+lamivudine+zidovudine, amprenavir, atazanavir, atazanavir sulfate, AZT, capravirine, darunavir, ddC, ddI, delavirdine, delavirdine mesylate, dolutegravir, doravirine, efavirenz, efavirenz+emtricitabine+tenofovir DF, 4′-ethynyl-2-fluoro-2′-deoxyadenosine, elvitegravir, emtricitabine, emtricitabine+tenofovir DF, emvirine, enfuvirtide, enteric coated didanosine, etravirine, fosamprenavir calcium, indinavir, indinavir sulfate, lamivudine, lamivudine+zidovudine, lopinavir, lopinavir+ritonavir, maraviroc, nelfinavir, nelfinavir mesylate, nevirapine, PPL-100, raltegravir, rilpivirine, ritonavir, saquinavir, saquinavir mesylate, stavudine, tipranavir and vicriviroc.

63. The compound

64. A pharmaceutical composition comprising an effective amount of the compound of claim 63 and a pharmaceutically acceptable carrier.

65. The pharmaceutical composition of claim 64 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.

66. The pharmaceutical composition of claim 65 comprising an effective amount of one or more additional HIV antiviral agent selected from: abacavir, abacavir sulfate, abacavir+lamivudine, abacavir+lamivudine+zidovudine, amprenavir, atazanavir, atazanavir sulfate, AZT, capravirine, darunavir, ddC, ddI, delavirdine, delavirdine mesylate, dolutegravir, doravirine, efavirenz, efavirenz+emtricitabine tenofovir DF, 4′-ethynyl-2-fluoro-2′-deoxyadenosine, elvitegravir, emtricitabine, emtricitabine+tenofovir DF, emvirine, enfuvirtide, enteric coated didanosine, etravirine, fosamprenavir calcium indinavir, indinavir sulfate, lamivudine, lamivudine+zidovudine, lopinavir, lopinavir+ritonavir, maraviroc, nelfinavir, nelfinavir mesylate, nevirapine, PPL-100, raltegravir, rilpivirine, ritonavir, saquinavir, saquinavir mesylate, stavudine, tipranavir and vicriviroc.

67. A method for the treatment of infection by HIV or for the treatment of 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 63 .

68. The method of claim 67 wherein the subject is human.

69. The method of claim 68 further comprising administering to the human 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.

70. The method of claim 69 comprising an effective amount of one or more additional HIV antiviral agent selected from: abacavir, abacavir sulfate, abacavir+lamivudine, abacavir+lamivudine+zidovudine, amprenavir, atazanavir, atazanavir sulfate, AZT, capravirine, darunavir, ddC, ddI, delavirdine, delavirdine mesylate, dolutegravir, doravirine, efavirenz, efavirenz+emtricitabine+tenofovir DF, 4′-ethynyl-2-fluoro-2′-deoxyadenosine, elvitegravir, emtricitabine, emtricitabine+tenofovir DF, emvirine, enfuvirtide, enteric coated didanosine, etravirine, fosamprenavir calcium, indinavir, indinavir sulfate, lamivudine, lamivudine+zidovudine, lopinavir, lopinavir+ritonavir, maraviroc, nelfinavir, nelfinavir mesylate, nevirapine, PPL-100, raltegravir, rilpivirine, ritonavir, saquinavir, saquinavir mesylate, stavudine, tipranavir and vicriviroc.

71. A compound that is a pharmaceutically acceptable salt of

72. A pharmaceutical composition comprising an effective amount of the compound of claim 71 and a pharmaceutically acceptable carrier.

73. The pharmaceutical composition of claim 72 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.

74. The pharmaceutical composition of claim 73 comprising an effective amount of one or more additional HIV antiviral agent selected from: abacavir, abacavir sulfate, abacavir+lamivudine, abacavir+lamivudine+zidovudine, amprenavir, atazanavir, atazanavir sulfate, AZT, capravirine, darunavir, ddC, ddI, delavirdine, delavirdine mesylate, dolutegravir, doravirine, efavirenz, efavirenz+emtricitabine+tenofovir DF, 4′-ethynyl-2-fluoro-2′-deoxyadenosine, elvitegravir, emtricitabine, emtricitabine+tenofovir DF, emvirine, enfuvirtide, enteric coated didanosine, etravirine, fosamprenavir calcium, indinavir, indinavir sulfate, lamivudine, lamivudine+zidovudine, lopinavir, lopinavir+ritonavir, maraviroc, nelfinavir, nelfinavir mesylate, nevirapine, PPL-100, raltegravir, rilpivirine, ritonavir, saquinavir, saquinavir mesylate, stavudine, tipranavir and vicriviroc.

75. A method for the treatment of infection by HIV or for the 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 71 .

76. The method of claim 75 wherein the subject is human.

77. The method of claim 76 further comprising administering to the human 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.

78. The method of claim 77 comprising an effective amount of one or more additional HIV antiviral agent selected from: abacavir, abacavir sulfate, abacavir+lamivudine, abacavir+lamivudine+zidovudine, amprenavir, atazanavir, atazanavir sulfate, AZT, capravirine, darunavir, ddC, ddI, delavirdine, delavirdine mesylate, dolutegravir, doravirine, efavirenz, efavirenz+emtricitabine+tenofovir DF, 4′-ethynyl-2-fluoro-2′-deoxyadenosine, elvitegravir, emtricitabine, emtricitabine+tenofovir DF, emvirine, enfuvirtide, enteric coated didanosine, etravirine, fosamprenavir calcium, indinavir, indinavir sulfate, lamivudine, lamivudine+zidovudine, lopinavir, lopinavir+ritonavir, maraviroc, nelfinavir, nelfinavir mesylate, nevirapine, PPL-100, raltegravir, rilpivirine, ritonavir, saquinavir, saquinavir mesylate, stavudine, tipranavir and vicriviroc.

79. The compound of claim 6 , or a pharmaceutically acceptable salt thereof, wherein R A is

80. The compound of claim 7 , or a pharmaceutically acceptable salt thereof, wherein R A is

81. The method of claim 13 comprising an effective amount of one or more additional HIV antiviral agent selected from: abacavir, abacavir sulfate, abacavir +lamivudine, abacavir+ lamivudine -F- zidovudine, amprena.vir, ata.zanavir, atazanavir sulfate, AZT, capravirine, darunavir, ddC, ddI, delavirdine, delavirdine mesylate, dolutegravir, doravirine, efavirenz, efavirenz +emtricitabine +tenofovir DF, 4′-ethynyl-2-fluoro-2′-deoxyadenosine, elvitegravir, emtricitabine, emtricitabine H- tenofovir DF, emvirine, enfuvirtide, enteric coated didanosine, etravirine, fosamprenavir calcium, indinavir, indinavir sulfate, lamivudine, lamivudine +zidovudine, lopinavir, lopinavir +ritonavir, maraviroc, nelfinavir, nelfinavir mesylate, nevirapine, PPL-100, raltegravir, rilpivirine, ritonavir, saquinavir, saquinavir mesylate, stavudine, tipranavir and vicriviroc.