Tetracyclic heterocycle compounds useful as HIV integrase inhibitors

1. A compound having the formula:

or a pharmaceutically acceptable salt thereof,

wherein:

----- represents an optional double bond;

ring A, inclusive of the carbon atom and nitrogen atom to which ring A is fused, is a 5- to 8-membered monocyclic or bicyclic heterocycloalkyl group, which can be optionally and independently substituted on ring A carbon atom with a group selected from C 1 -C 6 alkyl, —O—(C 1 -C 6 alkyl) and C 3 -C 7 cycloalkyl, and which can be optionally and independently substituted on a ring nitrogen atom with a group selected from C 1 -C 6 alkyl, —C(O)—(C 1 -C 6 alkyl) and —S(O) 2 —(C 1 -C 6 alkyl);

X is selected from 5 or 6-membered monocyclic heteroaryl and —N(R 4 )C(O)—;

R 1 is a phenyl group which is optionally substituted with from 1 to 3 groups, each independently selected from C 1 -C 6 alkyl, halo, —O—(C 1 -C 6 alkyl), C 1 -C 6 haloalkyl, —O—(C 1 -C 6 haloalkyl), —CN, —NO 2 , —N(R 4 ) 2 , —C(O)OR 6 , —C(O)N(R 4 ) 2 and —NHC(O)R 6 ;

R 2 is selected from H, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, halo, C 1 -C 6 haloalkyl, —OR 5 , —N(R 4 ) 2 , —C(O)R 5 , —C(O)N(R 4 ) 2 and —NHC(O)R 5 , wherein said C 1 -C 6 alkyl group is optionally substituted with one or more groups, each independently selected from halo, —OH, —O(C 1 -C 6 alkyl) and —N(R 4 ) 2 ;

R 3 is selected from H, C 1 -C 6 alkyl and —O—(C 1 -C 6 alkyl), —N(R 4 ) 2 ;

each occurrence of R 4 is independently selected from H and C 1 -C 6 alkyl;

each occurrence of R 5 is independently selected from H, C 1 -C 6 alkyl and C 3 -C 7 cycloalkyl;

each occurrence of R 6 is independently selected from H and C 1 -C 6 alkyl; and

R 7 is selected from H and C 1 -C 6 alkyl.

2. The compound of claim 1 , wherein X is —NHC(O)— or thiadiazolyl, or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 , wherein the optional double bond represented by

---- is not present, or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1 , wherein R 2 is H or —O—(C 1 -C 6 alkyl), or a pharmaceutically acceptable salt thereof.

5. The compound of claim 1 , wherein R 3 is H, or a pharmaceutically acceptable salt thereof.

6. The compound of claim 1 , wherein ring A is selected from:

or a pharmaceutically acceptable salt thereof.

7. The compound of claim 1 , wherein the compound of formula (I) has the formula (Ia):

or a pharmaceutically acceptable salt thereof,

wherein

ring A, inclusive of the carbon atom and nitrogen atom to which ring A is fused, is selected from:

R 1 is a phenyl group which is optionally substituted with from 1 to 3 groups, each independently selected from C 1 -C 6 alkyl, halo and —O—(C 1 -C 6 alkyl);

R 2 is selected from H and O—(C 1 -C 6 alkyl); and

R 7 is selected from H and C 1 -C 6 alkyl.

8. The compound of claim 1 , wherein R 1 is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

9. The compound of claim 1 , wherein R 7 is H, or a pharmaceutically acceptable salt thereof.

10. A compound of claim 1 selected from

or a pharmaceutically acceptable salt thereof.

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

12. The pharmaceutical composition of claim 11 , further comprising one or more additional therapeutic agents selected from: lamivudine, abacavir, ritonavir, darunavir, atazanavir, emtricitabine, tenofovir, rilpivirine and lopinavir.

13. A compound having the structure:

or a pharmaceutically acceptable salt thereof.

14. The compound of claim 13 having the structure:

15. A pharmaceutically acceptable salt of the compound of claim 13 .

16. A pharmaceutical composition comprising the compound of claim 13 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

17. A compound having the structure:

or a pharmaceutically acceptable salt thereof.

18. The compound of claim 17 having the structure:

19. A pharmaceutically acceptable salt of the compound of claim 17 .

20. A pharmaceutical composition comprising the compound of claim 17 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

21. A compound having the structure:

or a pharmaceutically acceptable salt thereof.

22. The compound of claim 21 having the structure:

23. A pharmaceutically acceptable salt of the compound of claim 21 .

24. A pharmaceutical composition comprising the compound of claim 21 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

25. A compound having the structure:

or a pharmaceutically acceptable salt thereof.

26. The compound of claim 25 having the structure:

27. A pharmaceutically acceptable salt of the compound of claim 25 .

28. A pharmaceutical composition comprising the compound of claim 25 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

29. A compound having the structure:

or a pharmaceutically acceptable salt thereof.

30. The compound of claim 29 having the structure:

31. A pharmaceutically acceptable salt of the compound of claim 29 .

32. A pharmaceutical composition comprising the compound of claim 29 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

33. A compound having the structure:

or a pharmaceutically acceptable salt thereof.

34. The compound of claim 33 having the structure:

35. A pharmaceutically acceptable salt of the compound of claim 33 .

36. A pharmaceutical composition comprising the compound of claim 33 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

37. A method for the inhibition of HIV integrase in a subject in need thereof which comprises administering to the subject an effective amount of the compound according to claim 1 , or a pharmaceutically acceptable salt thereof.

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

39. A method for the treatment of infection by HIV or for the treatment or delay in the onset or progression of AIDS in a subject in need thereof, which comprises administering to the subject an effective amount of the compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and one or more additional therapeutic agents selected from: abacavir, lamivudine, ritonavir and lopinavir, wherein the amounts administered of the compounds, are together effective to treat infection by HIV or to treat, prevent or delay the onset or progression of AIDS.