Heterocyclic compounds as HIV protease inhibitors

1. A compound of structural Formula I:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is selected from hydrogen, halogen, C 1-3 alkyl, C 1-3 haloalkyl, —OC 1-3 haloalkyl, CN, —C(O)NHC 1-6 alkyl and —SO 2 C 1-6 alkyl;

R 2 is selected from C 6-10 aryl, C 1-6 alkyl, (CH 2 ) k C 1-3 haloalkyl, (CH 2 ) k C 3-6 cycloalkyl, (CH 2 ) k C 6-10 aryl, (CH 2 ) k C 5-10 heterocycloalkyl and (CH 2 ) k C 5-10 heteroaryl, wherein R 2 is substituted with 0, 1, 2 or 3 of R 6 selected from halogen, hydroxy, and C 1-4 alkoxy;

R 3 is selected from hydrogen, C 1-4 alkyl, C 3-8 cycloalkyl C 1-6 alkyl, C 3-8 cycloalkyl, and C 1-4 haloalkyl, wherein R 3 is substituted with 0, 1, 2 or 3 of R 7 selected from halogen and hydroxy;

R 4 is selected from C 1-6 alkyl carbonyl, C 1-6 alkylcarboxy, cyclopropylcarboxy and

C 3-8 alkylcycloalkylcarboxy, wherein R 4 is substituted with 0, 1, 2, or 3 of R 8 selected from C 1-6 alkyl and halogen;

R 5 is selected from C 3-8 cycloalkyl C 1-6 alkyl, C 3-8 heterocycloalkyl C 1-6 alkyl, C 6-10 aryl C 1-6 alkyl, and C 5-10 heteroaryl C 1-6 alkyl, R 5 is substituted with 0, 1, or 2 of R 9 selected from C 1-5 alkyl, cyano, C 1-6 alkoxy, and halogen;

n is 1, 2, 3, 4, 5, or 6;

p is 0, 1, 2, or 3; and

k is 0, 1, 2, 3, or 4.

2. The compound according to claim 1 wherein R 2 is phenyl, isopentyl, or isobutyl, wherein R 2 is substituted by 0, 1, 2, or 3 of fluoro.

3. The compound according to claim 1 wherein R 3 is selected from hydrogen, methyl, cyclopropylmethyl, cyclopropyl, methylethyl, trifluoromethyl, ethyl, and cyclopropyl ethyl, wherein R 3 is substituted by 0, 1, or 2 of fluoro.

4. The compound according to claim 1 wherein R 4 is selected from, methylcarbonyl, methylcarboxy, ethylcarboxy, cyclopropylcarboxy and isopropylcarboxy, wherein R 4 is substituted by 0, 1, or 2 of methyl or fluoro.

5. The compound according to claim 1 wherein R 5 is selected from benzyl, phenylethyl, pyridinylmethyl, naphalenylmethyl, and cyclohexylmethyl, wherein R 5 is substituted by 0, 1, or 2 of cyano, methoxy, fluoro, or chloro.

6. The compound according to claim 5 wherein n is 3, 4 or 5.

7. The compound according to claim 6 wherein p is 0, 1 or 2.

8. A compound which is:

N-{4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]-1-methylbutyl}-N-alpha-(methoxycarbonyl)-O-methyl-L-tyrosinamide;

N-alpha-acetyl-N-[4-(2-imino-5-oxo-4,4-diphenylimidazolidin-1-yl)butyl]-L-phenylalaninamide;

N-[4-(2-imino-5-oxo-4,4-diphenylimidazolidin-1-yl)butyl]-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

2-amino-N-[4-(2-imino-5-oxo-4,4-diphenylimidazolidin-1-yl)butyl]-4-phenylbutanamide;

N-alpha-(ethoxycarbonyl)-N-[4-(2-imino-5-oxo-4,4-diphenylimidazolidin-1-yl)butyl]-L-phenylalaninamide;

N-[4-(2-imino-5-oxo-4,4-diphenylimidazolidin-1-yl)-1-methylbutyl]-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

methyl [2-{[4-(2-imino-5-oxo-4,4-diphenylimidazolidin-1-yl)butyl]amino}-2-oxo-1-(pyridin-3-ylmethyl)ethyl]carbamate;

N-[4-(2-imino-5-oxo-4,4-diphenylimidazolidin-1-yl)butyl]-3-pyridin-3-yl-L-alaninamide;

N-[4-(2-imino-5-oxo-4,4-diphenylimidazolidin-1-yl)butyl]-3-pyridin-4-yl-L-alaninamide;

N-{4-[4,4-bis(4-fluorophenyl)-2-imino-5-oxoimidazolidin-1-yl]-1-methylbutyl}-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

methyl [2-{[4-(2-imino-5-oxo-4,4-diphenylimidazolidin-1-yl)butyl]amino}-2-oxo-1-(pyridin-2-ylmethyl)ethyl]carbamate;

methyl [2-{[4-(2-imino-5-oxo-4,4-diphenylimidazolidin-1-yl)butyl]amino}-2-oxo-1-(pyridin-4-ylmethyl)ethyl]carbamate;

N-[5-(2-imino-5-oxo-4,4-diphenylimidazolidin-1-yl)pentyl]-L-phenylalaninamide;

N-[5-(2-imino-5-oxo-4,4-diphenylimidazolidin-1-yl)pentyl]-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

N-{4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]butyl}-L-phenylalaninamide;

N-{4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]butyl}-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

N-{4-[2-imino-4-(3-methylbutyl)-5-oxo-4-phenylimidazolidin-1-yl]butyl}-L-phenylalaninamide;

N-{4-[2-imino-4-(3-methylbutyl)-5-oxo-4-phenylimidazolidin-1-yl]butyl)}-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

methyl [2-{[5-(2-imino-5-oxo-4,4-diphenylimidazolidin-1-yl)pentyl]amino}-2-oxo-1-(pyridin-4-ylmethyl)ethyl]carbamate;

methyl [2-({4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]butyl}amino)-2-oxo-1-(pyridin-4-ylmethyl)ethyl]carbamate;

methyl [2-({4-[2-imino-4-(3-methylbutyl)-5-oxo-4-phenylimidazolidin-1-yl]butyl}amino)-2-oxo-1-(pyridin-4-ylmethyl)ethyl]carbamate;

N-[4-(2-imino-5-oxo-4,4-diphenylimidazolidin-1-yl)butyl]-N-alpha-{[(1-methylcyclopropyl)oxy]carbonyl}-L-phenylalaninamide;

3-cyano-N-[4-(2-imino-5-oxo-4,4-diphenylimidazolidin-1-yl)butyl]-L-phenylalaninamide;

4-fluoro-N-[4-(2-imino-5-oxo-4,4-diphenylimidazolidin-1-yl)butyl]-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

N-[4-(2-imino-5-oxo-4,4-diphenylimidazolidin-1-yl)butyl]-N-alpha-[(1-methylethoxy)carbonyl]-L-phenylalaninamide;

4-fluoro-N-{4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]-1-methylbutyl}-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

N-{4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]-1-methylbutyl)}-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

N-{1-(cyclopropylmethyl)-4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]butyl}-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

3-chloro-N-{1-(cyclopropylmethyl)-4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]butyl}-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

2-chloro-N-{1-(cyclopropylmethyl)-4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]butyl}-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

3-chloro-N-{1-cyclopropyl-4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]butyl}-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

2-chloro-N-{1-cyclopropyl-4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]butyl}-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

2-chloro-N-{4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]-1-methylbutyl}-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

3-chloro-N-{4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]-1-methylbutyl}-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

N-{1-cyclopropyl-4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]butyl}-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

4-chloro-N-{4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]-1-methylbutyl}-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

methyl [2-({4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]-1-methylbutyl}amino)-1-(naphthalen-1-ylmethyl)-2-oxoethyl]carbamate;

N-{4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]-1-methylbutyl)}-2-methoxy-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

N-{4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]-1-methylbutyl}-3-methoxy-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

methyl [1-(cyclohexylmethyl)-2-({4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]-1-methylbutyl}amino)-2-oxoethyl]carbamate;

methyl (1-((5-(2-imino-4-isobutyl-5-oxo-4-phenylimidazolidin-1-yl)pentan-2-yl)amino)-3-(naphthalen-2-yl)-1-oxopropan-2-yl)carbamate;

3-chloro-N-[4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]-1-(1-methylethyl)butyl]-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

2-chloro-N-[4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]-1-(1-methylethyl)butyl]-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

N-[4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]-1-(1-methylethyl)butyl]-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

N-[4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]-1-(trifluoromethyl)butyl]-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

N-{1-ethyl-4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]butyl}-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

4-chloro-N-{1-ethyl-4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]butyl}-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

3-chloro-N-{1-ethyl-4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]butyl}-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

2-chloro-N-{1-ethyl-4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]butyl}-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

N-{4-cyclopropyl-4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]butyl)}-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

N-{5-cyclopropyl-4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]pentyl)}-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

N-{4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]pentyl}-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

N-{4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazolidin-1-yl]hexyl}-N-alpha-(methoxycarbonyl)-L-phenylalaninamide; or

N-{6-cyclopropyl-4-[2-imino-4-(2-methylpropyl)-5-oxo-4-phenylimidazoidin-1-yl]hexyl)}-N-alpha-(methoxycarbonyl)-L-phenylalaninamide;

or a pharmaceutically acceptable salt thereof.

9. A compound which is:

No.

1

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

31

32

33

34

35

36

37

38

39

40

41

42

43

44

45

46

47

48

49

50

51

52

53

54

55

or

56

or a pharmaceutically acceptable salt thereof.

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

11. A method for the treatment or prophylaxis of infection by HIV or for the treatment, prophylaxis, 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. A pharmaceutical composition comprising an effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier and further comprising an effective amount of an anti-HIV agent selected from the group consisting of HIV antiviral agents, immunomodulators, and anti-infective agents.

13. The pharmaceutical composition of claim 12 , wherein the anti-HIV agent is an antiviral selected from the group consisting of HIV protease inhibitors, HIV reverse transcriptase inhibitors, HIV integrase inhibitors, HIV fusion inhibitors, HIV entry inhibitors, and HIV maturation inhibitors.