Tricyclic heterocycle compounds useful as HIV integrase inhibitors

1. A compound having the formula:

or a pharmaceutically acceptable salt thereof,

wherein:

A is —CH(R 2 )—;

X is 5 or 6-membered monocyclic heteroaryl or —N(R 5 )(C═O);

Y is selected from —O—, —N(R 5 )— or —CH(R 3 )—, or -A-Y— is —C(R 2 )═CH—;

Z is —CH(R 4 )— or a bond, such that: (i) when Y is —O— or —N(R 5 )—, then Z is a bond, (b) when Y is —CH(R 3 )—, then Z is a bond or —CH(R 4 ), and (iii) when -A-Y— is —C(R 2 )═CH—, then Z is a bond;

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 —NH(C═O)R 6 ;

R 2 is selected from H, C 1 -C 6 alkyl, —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);

each occurrence of R 4 is independently selected from H, C 1 -C 6 alkyl and —O—(C 1 -C 6 alkyl);

each occurrence of R 5 is independently H or C 1 -C 6 alkyl;

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

R 7A is H;

R 7B is H, or R 7A and R 7B , together with the common carbon atom to which they are each attached, join to form a spirocyclic C 3 -C 7 cycloalkyl group or a spirocyclic 4- to 7-membered monocyclic heterocycloalkyl group; and

R 8 is selected from C 1 -C 6 alkyl, —(C 1 -C 6 alkylene)-O—(C 1 -C 6 alkyl), C 3 -C 7 cycloalkyl and —(C 1 -C 6 alkylene)-C 3 -C 7 cycloalkyl.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof,

wherein:

the group -A-Y—Z— is selected from —CH(R 2 )CH 2 —, —CH(R 2 )—CH(R 3 )—CH(R 4 )— and —C(R 2 )═CH—;

X is diazolyl or —N(R 5 )(C═O);

R 1 is a phenyl group which is optionally substituted with from 1 to 3 groups, each independently selected from Cl and F;

R 2 is H or —O—(C 1 -C 6 alkyl);

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

each occurrence of R 5 is independently H or C 1 -C 6 alkyl;

R 7A is H;

R 7B is H, or R 7A and R 7B , together with the common carbon atom to which they are each attached, join to form a spirocyclic 4- to 7-membered monocyclic heterocycloalkyl group; and

R 8 is selected from C 1 -C 6 alkyl, —(C 1 -C 6 alkylene)-O—(C 1 -C 6 alkyl) and —(C 1 -C 6 alkylene)-C 3 -C 7 cycloalkyl.

3. The compound of claim 1 , wherein the -A-Y—Z— group is —CH(R 2 )—CH 2 —, or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1 , wherein the -A-Y—Z— group is —CH(R 2 )—CH(R 3 )— CH(R 4 )—, or a pharmaceutically acceptable salt thereof.

5. The compound of claim 1 , wherein the -A-Y—Z— group is —C(R 2 )═CH—, or a pharmaceutically acceptable salt thereof.

6. The compound of claim 1 , wherein X is —NH(C═O), or a pharmaceutically acceptable salt thereof.

7. The compound of claim 1 , wherein X is 5-membered heteroaryl, or a pharmaceutically acceptable salt thereof.

8. The compound of claim 1 , wherein R 1 is phenyl, which is substituted with from 1-3 groups, each independently selected from F and Cl, or a pharmaceutically acceptable salt thereof.

9. The compound of claim 1 , wherein R 1 is selected from:

or a pharmaceutically acceptable salt thereof.

10. The compound of claim 1 , wherein R 7A and R 7B are each H, or a pharmaceutically acceptable salt thereof.

11. The compound of claim 1 , wherein R 7A and R 7B , together with the common carbon atoms to which they are attached, join to form a 4 to 7-membered heterocycloalkyl group, or a pharmaceutically acceptable salt thereof.

12. The compound of claim 1 , wherein R 8 is methyl, ethyl, isopropyl, —CH 2 CH 2 OCH 3 and —CH 2 -cyclopropyl, or a pharmaceutically acceptable salt thereof.

13. A compound selected from:

or a pharmaceutically acceptable salt thereof.

14. 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.

15. 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.

16. The pharmaceutical composition of claim 14 , further comprising one or more additional therapeutic agents selected from, lamivudine, abacavir, ritonavir, darunavir, atazanavir, emtricitabine, tenofovir, rilpivirine and lopinavir.

17. The method of claim 15 , further comprising administering to the subject one or more additional therapeutic agents selected from, abacavir, lamivudine, ritonavir and lopinavir, wherein the amounts administered of the compound of claim 1 and the one or more additional therapeutic agents, are together effective to treat infection by HIV or to treat or delay the onset or progression of AIDS.