FUSED TRICYCLIC HETEROCYCLIC COMPOUNDS AS HIV INTEGRASE INHIBITORS

1 . A compound having the formula:

or a pharmaceutically acceptable salt or prodrug thereof,

wherein:

R 1 is C 1 -C 6 alkyl or —(C 2 -C 6 alkenyl)-O—(C 1 -C 6 alkyl);

R 2 is phenyl, which is optionally substituted with up to 3 ring substituent groups, each independently selected from halo;

R 3 is —N(R 4 ) 2 ;

each occurrence of R 4 is independently selected from H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 7 cycloalkyl, —CH 2 —(C 3 -C 7 cycloalkyl), phenyl, benzyl, —C(O)—C(O)—N(R 5 ) 2 , —S(O) 2 —C 1 -C 6 alkyl, —S(O) 2 -phenyl, —(C 2 -C 6 alkenyl)-O—(C 1 -C 6 alkyl) and —C(O)—C 1 -C 6 alkyl, where the phenyl moiety of a —S(O) 2 -phenyl group can be optionally substituted with a C 1 -C 6 alkyl group; or both R 4 groups, and the common nitrogen atom to which they are attached, join to form an azetidinyl, piperidinyl, or pyrrolidinyl group; and

each occurrence of R 5 is independently selected from H and C 1 -C 6 alkyl.

2 . The compound of claim 1 , having the formula (Ia), (Ib), (Ic) or (Id):

or a pharmaceutically acceptable salt or prodrug thereof.

3 . The compound of claim 1 , wherein R 1 is C 1 -C 6 alkyl, or a pharmaceutically acceptable salt or prodrug thereof.

4 . The compound of claim 3 , wherein R 1 is ethyl, or a pharmaceutically acceptable salt or prodrug thereof.

5 . The compound of claim 1 , wherein R 2 is selected from:

or a pharmaceutically acceptable salt or prodrug thereof.

6 . The compound of claim 5 , wherein R 2 is:

or a pharmaceutically acceptable salt or prodrug thereof.

7 . The compound of claim 1 , wherein R 3 is —N(R 4 ) 2 , wherein each occurrence of R 4 is independently selected from H and C 1 -C 6 alkyl, or a pharmaceutically acceptable salt or prodrug thereof.

8 . The compound of claim 7 , wherein R 3 is —NHCH 2 CH 3 , or a pharmaceutically acceptable salt or prodrug thereof.

9 . The compound of claim 1 , wherein R 1 is selected from methyl, ethyl, or n-propyl; R 2 is selected from:

R 3 is selected from —NH 2 , —NHCH 3 , —NHCH 2 CH 3 , —NHCH 2 CH 2 CH 3 , —NHCH 2 -cyclopropyl, —NH-benzyl, —NHCH 2 CH 2 OCH 3 , —NHCH 2 CH 2 CF 3 , —NHCD 2 CD 3 , pyrrolidinyl, —N(CH 3 ) 2 , azetidinyl, —N(CH 2 ) 3 C, —NHS(O) 2 CH 3 , —NHS(O) 2 -(p-toluene), —NHC(O)CH 3 and —NHC(O)C(O)N(CH 3 ) 2 , or a pharmaceutically acceptable salt or prodrug thereof.

10 . A compound selected from:

or a pharmaceutically acceptable salt or prodrug thereof.

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

12 . 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 or prodrug thereof.

13 . A method for the treatment of infection by HIV or for the treatment, prophylaxis, 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 or prodrug thereof.

14 . (canceled)

15 . (canceled)

16 . The pharmaceutical composition of claim 11 , further comprising one or more additional therapeutic agents selected from raltegravir, lamivudine, abacavir, ritonavir, dolutegravir, arunavir, atazanavir, emtricitabine, tenofovir, elvitegravir, rilpivirine and lopinavir.

17 . A method for the treatment of infection by HIV or for the treatment, prophylaxis, 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 and one or more additional therapeutic agents selected from raltegravir, 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, prevent or delay the onset or progression of AIDS.