Inhibitors of human immunodeficiency virus replication

1. A compound of the formula (I)

wherein

represents either a single or double bond;

X is S or CR 5 ;

Y is S or CR 7 ;

wherein one of X or Y is S;

R 2 , R 5 , R 6 and R 7 are each independently selected from:

a) halo;

b) R 8 , —C(═O)—R 8 , —C(═O)—O—R 8 , —O—R 8 , —S—R 8 , SO—R 8 , —SO 2 —R 8 , —(C 1-6 )alkylene-R 8 , —(C 1-6 )alkylene-C(═O)—R 8 , —(C 1-6 )alkylene-C(═O)—O—R 8 , —(C 1-6 )alkylene-SO—R 8 or —(C 1-6 )alkylene-SO 2 —R 8 , —(C 1-6 )alkylene-O—R 8 or —(C 1-6 )alkylene-S—R 8 ;

wherein R 8 is in each instance independently selected from H, (C 1-6 )alkyl, (C 2-6 )alkenyl, (C 2-6 )alkynyl, (C 1-6 )haloalkyl, (C 3-7 )cycloalkyl, aryl and Het;

and

wherein each of the aryl and Het is optionally substituted with 1 to 3 substituents each independently selected from:

i) halo, oxo, thioxo, (C 2-6 )alkenyl, (C 1-6 )haloalkyl, (C 3-7 )cycloalkyl, (C 3-7 )cycloalkyl-(C 1-6 )alkyl-, —OH, —O(C 1-6 )alkyl, —O(C 1-6 )haloalkyl, —SH, —S(C 1-6 )alkyl, —SO(C 1-6 )alkyl, —SO 2 (C 1-6 )alkyl, —NH 2 , —NH(C 1-6 )alkyl and —N((C 1-6 )alkyl) 2 ;

ii) (C 1-6 )alkyl optionally substituted with —OH, —O—(C 1-6 )haloalkyl, or —O—(C 1-6 )alkyl; and

iii) aryl or Het, wherein each of the aryl and Het is optionally substituted with halo or (C 1-6 )alkyl; and

c) —N(R 9 )R 10 , —C(═O)—N(R 9 )R 10 , —O—C(═O)—N(R 9 )R 10 , —SO 2 —N(R 9 )R 10 , —(C 1-6 )alkylene-N(R 9 )R 10 , —(C 1-6 )alkylene-C(═O)—N(R 9 )R 10 , —(C 1-6 )alkylene-O—C(═O)—N(R 9 )R 10 , or —(C 1-6 )alkylene-SO 2 —N(R 9 )R 10 wherein

R 9 is in each instance independently selected from H, (C 1-6 )alkyl and (C 3-7 )cycloalkyl; and

R 10 is in each instance independently selected from R 8 , —(C 1-6 )alkylene-R 8 , —SO 2 —R 8 , —C(═O)—R 8 , —C(═O)OR 8 and —C(═O)N(R 9 )R 8 ; wherein R 8 and R 9 are as defined above;

R 3 is (C 1-6 )alkyl, (C 1-6 )haloalkyl, (C 2-6 )alkenyl, (C 2-6 )alkynyl, (C 3-7 )cycloalkyl-(C 1-6 )alkyl-, aryl-(C 1-6 )alkyl-, Het-(C 1-6 )alkyl- or —W—R 31 , and bond c is a single bond; or

R 3 is (C 1-6 )alkylidene and bond c is a double bond;

wherein W is O or S and R 31 is (C 1-6 )alkyl, (C 1-6 )haloalkyl, (C 2-6 )alkenyl, (C 2-6 )alkynyl, (C 3-7 )cycloalkyl, aryl, (C 3-7 )cycloalkyl-(C 1-6 )alkyl-, aryl-(C 1-6 )alkyl- or Het-(C 1-6 )alkyl-;

wherein each of the (C 1-6 )alkylidene, (C 1-6 )alkyl, (C 1-6 )haloalkyl, (C 2-6 )alkenyl, (C 2-6 )alkynyl, (C 3-7 )cycloalkyl-(C 1-6 )alkyl-, aryl-(C 1-6 )alkyl-, Het-(C 1-6 )alkyl- and —W—R 31 is optionally substituted with 1 to 3 substituents each independently selected from (C 1-6 )alkyl, halo, cyano, oxo and —O(C 1-6 )alkyl;

R 4 is aryl or Het, wherein each of the aryl and Het is optionally substituted with 1 to 5 substituents each independently selected from halo, (C 1-6 )alkyl, (C 2-6 )alkenyl, (C 1-6 )haloalkyl, (C 3-7 )cycloalkyl, (C 3-7 )cycloalkyl-(C 1-6 )alkyl-, —OH, —O(C 1-6 )alkyl, —SH, —S(C 1-6 )alkyl, —NH 2 , —NH(C 1-6 )alkyl and —N((C 1-6 )alkyl) 2 ; wherein the (C 1-6 )alkyl is optionally substituted with hydroxy, —O(C 1-6 )alkyl, cyano or oxo;

and

wherein Het is a 4- to 7-membered saturated, unsaturated or aromatic heterocycle having 1 to 4 heteroatoms each independently selected from O, N and S, or a 7- to 14-membered saturated, unsaturated or aromatic heteropolycycle having wherever possible 1 to 5 heteroatoms, each independently selected from O, N and S; wherein each N heteroatom may, independently and where possible, exist in an oxidized state such that it is further bonded to an oxygen atom to form an N-oxide group and wherein each S heteroatom may, independently and where possible, exist in an oxidized state such that it is further bonded to one or two oxygen atoms to form the groups SO or SO 2 ;

or a salt thereof.

2. A compound according to claim 1 of the formula (Ie), or a pharmaceutically acceptable salt thereof:

wherein R 2 , R 3 , R 4 , R 5 and R 6 are as defined in claim 1 .

3. A compound according to claim 1 of the formula (Ih), or a pharmaceutically acceptable salt thereof:

wherein R 2 , R 3 , R 4 , R 6 and R 7 are as defined in claim 1 .

4. A compound according to any one of claims 1 to 3 , or a pharmaceutically acceptable salt thereof, wherein R 2 is (C 1-6 )alkyl or —O(C 1-6 )alkyl.

5. A compound according to any one of claims 1 to 3 , or a pharmaceutically acceptable salt thereof, wherein R 3 is —O(C 1-4 )alkyl; wherein the —O(C 1-4 )alkyl is optionally substituted with 1 to 2 substituents each independently selected from cyano, oxo and —O(C 1-6 )alkyl; and

bond c is a single bond.

6. A compound according to any one of claims 1 to 3 , or a pharmaceutically acceptable salt thereof, wherein R 4 is phenyl optionally substituted with 1 to 3 substituents each independently selected from F, Cl, Br, NH 2 , —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , CH 2 F, CF 3 and —CH 2 CH 2 F.

7. A compound according to any one of claims 1 to 3 , or a pharmaceutically acceptable salt thereof, wherein R 4 is Het optionally substituted with 1 or 2 substituents each independently selected from halo, (C 1-6 )alkyl and —O(C 1-6 )alkyl;

wherein the Het is a 5- or 6-membered heterocycle having 1 to 3 heteroatoms each independently selected from N, O and S; or the Het is a 9- or 10-membered heteropolycycle having 1 to 3 heteroatoms each independently selected from N, O and S.

8. A compound according to any one of claims 1 to 3 , or a pharmaceutically acceptable salt thereof, wherein R 4 is aryl or Het optionally substituted with 1 to 3 substituents each independently selected from halo, (C 1-6 )alkyl, (C 1-6 )haloalkyl, NH 2 and —O(C 1-6 )alkyl;

wherein the aryl is selected from:

and

wherein the Het is selected from:

9. A compound according to claim 1 or 2 , or a pharmaceutically acceptable salt thereof, wherein R 5 is H or (C 1-4 )alkyl.

10. A compound according to any one of claims 1 to 3 , or a pharmaceutically acceptable salt thereof, wherein R 6 is H or (C 1-4 )alkyl.

11. A compound according to claim 1 or 3 , or a pharmaceutically acceptable salt thereof, wherein R 7 is H or (C 1-4 )alkyl.

12. A pharmaceutical composition comprising a compound according to any one of claims 1 to 3 , or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

13. A method for treating HIV infection in a host infected by HIV which method comprises administering to said host a therapeutically effective amount of a compound according to any one of claims 1 to 3 , or a pharmaceutically acceptable salt thereof.