Inhibitors of human immunodeficiency virus replication

1. A compound of Formula I

wherein

R 1 is (C 1-6 )alkyl, (C 2-6 )alkenyl or (C 3-6 )cycloalkyl, wherein the (C 1-6 )alkyl is optionally substituted with —O(C 1-6 )alkyl or —S(C 1-6 )alkyl;

R 2 is (C 1-8 )alkyl or (C 3-8 )cycloalkyl, wherein the (C 3-8 )cycloalkyl is optionally substituted with (C 1-6 )alkyl;

R 3 is aryl, wherein the aryl is optionally fused to one or more cycles, at least one of which is a heterocycle, to form a heteropolycycle, and wherein the aryl or heteropolycycle is optionally substituted with 1 to 4 substituents each independently selected from (C 1-6 )alkyl, halo and —O(C 1-6 )alkyl;

R 4 is (C 1-6 )alkyl, —CN, halo, (C 1-6 )haloalkyl, (C 3-5 )cycloalkyl, or —O(C 1-6 )alkyl; and

a is a double bond, R 6 is absent and R 5 is R 51 or —(C 1-3 )alkyl-R 51 ; or

a is a single bond and R 5 and R 6 are joined, together with the atoms to which they are bonded, to form a 5-membered ring optionally having 1 to 3 further heteroatoms each independently selected from O, N and S, wherein the 5-membered ring is optionally substituted with 1 to 3 R 51 substituents;

wherein R 51 is in each case independently selected from R 52 , —OR 53 , —N(R 54 )R 53 , —C(═O)R 52 , —C(═O)OR 53 , —C(═O)N(R 54 )R 53 , —OC(═O)N(R 54 )R 53 , —N(R 54 )C(═O)R 52 , —N(R 54 )C(═O)N(R 54 )R 53 and —N(R 54 )C(═O)OR 53 ; wherein

R 52 is in each case independently selected from R 53 , (C 2-8 )alkenyl and (C 2-8 )alkynyl,

R 53 is in each case independently selected from (C 1-8 )alkyl, (C 3-8 )cycloalkyl, (C 3-8 )cycloalkyl-(C 1-6 )alkyl-, aryl, aryl-(C 1-6 )alkyl-, Het, and Het-(C 1-6 )alkyl-, and

R 54 is in each case independently selected from H and (C 1-3 )alkyl;

wherein each of R 52 and R 53 is optionally substituted with 1 to 3 substituents each independently selected from R 55 , halo, —CN, —OR 56 , —SR 56 , —SOR 56 , —SO 2 R 56 , —N(R 54 )R 56 , —N(R 54 )C(═O)R 55 , —N(R 54 )C(═O)N(R 54 )R 56 , —N(R 54 )C(═O)OR 56 , —OC(═O)N(R 54 )R 56 , —C(═O)R 55 , —C(═O)OR 56 , and —CON(R 54 )R 56 , wherein

R 55 is in each case independently selected from R 56 , (C 2-8 )alkenyl and (C 2-8 )alkynyl, and

R 56 is in each case independently selected from H, (C 1-8 )alkyl, (C 3-8 )cycloalkyl, (C 3-8 )cycloalkyl-(C 1-6 )alkyl-, aryl, aryl-(C 1-6 )alkyl-, Het, and Het-(C 1-6 )alkyl-,

wherein each of R 55 and R 56 is, where possible, in each case independently optionally substituted with 1 to 3 substituents each independently selected from (C 1-6 )alkyl, (C 1-6 )haloalkyl, halo, —OH, —O(C 1-6 )alkyl, —NH 2 , —NH(C 1-6 )alkyl, —N((C 1-6 )alkyl) 2 and —NH(C═O)(C 1-6 )alkyl;

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;

or a salt thereof.

2. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, having the formula:

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

3. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is

—CH 3 , —CH 2 OMe, —CH 2 OEt, —CH 2 SMe, —CH═CH 2 or

4. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is.

5. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is phenyl or a heteropolycycle selected from:

 wherein the phenyl or heteropolycycle is optionally substituted with 1 to 4 substituents each independently selected from (C 1-6 )alkyl, halo and —O(C 1-6 )alkyl.

6. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is (C 1-6 )alkyl, —CN, halo or (C 1-6 )haloalkyl.

7. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is —CH 3 .

8. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein a is a double bond, R 6 is absent and R 5 is R 51 or —(C 1-3 )alkyl-R 51 ;

wherein R 51 is selected from R 52 , —OR 53 , —C(═O)R 52 , —C(═O)OR 53 , —C(═O)N(R 54 )R 53 , —N(R 54 ) C (═O)R 52 , —N(R 54 )C(═O)N(R 54 )R 53 and —N(R 54 )C(═O)OR 53 ; wherein

R 52 is selected from R 53 and (C 2-8 )alkenyl, and

R 53 is selected from (C 1-8 )alkyl, (C 3-8 )cycloalkyl, (C 3-8 )cycloalkyl-(C 1-6 )alkyl-, aryl, aryl-(C 1-6 )alkyl-, Het, and Het-(C 1-6 )alkyl-,

wherein Het and the Het portion of Het-(C 1-6 )alkyl- are in each case independently selected from:

R 54 is in each case independently selected from H and (C 1-3 )alkyl;

wherein each of R 52 and R 53 is optionally substituted with 1 to 3 substituents each independently selected from R 56 , halo, —CN, —OR 56 , —SR 56 , —SO 2 R 56 , —N(R 54 )R 56 and —CON(R 54 )R 56 , wherein

R 56 is in each case independently selected from H, (C 1-8 )alkyl, (C 3-8 )cycloalkyl, (C 3-8 )cycloalkyl-(C 1-6 )alkyl-, aryl, aryl-(C 1-6 )alkyl-, Het, and Het-(C 1-6 )alkyl-,

wherein Het and the Het portion of Het-(C 1-6 )alkyl- are in each case independently selected from:

wherein R 56 is, where possible, in each case independently optionally substituted with 1 to 3 substituents each independently selected from (C 1-6 )alkyl, (C 1-6 )haloalkyl, halo, —O(C 1-6 )alkyl, —N((C 1-6 )alkyl) 2 and —NH(C═O)(C 1-6 )alkyl.

9. A compound of the formula:

wherein

R 1 is (C 1-6 )alkyl, (C 2-6 )alkenyl or (C 3-6 )cycloalkyl, wherein the (C 1-6 )alkyl is optionally substituted with —O(C 1-6 )alkyl or —S(C 1-6 )alkyl;

R 2 is (C 1-8 )alkyl or (C 3-8 )cycloalkyl, wherein the (C 3-8 )cycloalkyl is optionally substituted with (C 1-6 )alkyl;

R 3 is aryl, wherein the aryl is optionally fused to one or more cycles, at least one of which is a heterocycle, to form a heteropolycycle, and wherein the aryl or heteropolycycle is optionally substituted with 1 to 4 substituents each independently selected from (C 1-6 )alkyl, halo and —O(C 1-6 )alkyl;

R 4 is (C 1-6 )alkyl, —CN, halo, (C 1-6 )haloalkyl, (C 3-5 )cycloalkyl, or —O(C 1-6 )alkyl; and

a is a double bond, R 6 is absent and R 5 is R 51 or —(C 1-3 )alkyl-R 51 ; or

a is a single bond and R 5 and R 6 are joined, together with the atoms to which they are bonded, to form a 5-membered ring optionally having 1 to 3 further heteroatoms each independently selected from O, N and S, wherein the 5-membered ring is optionally substituted with 1 to 3 R 51 substituents;

wherein R 51 is in each case independently selected from R 52 , —OR 53 , —N(R 54 )R 53 , —C(═O)R 52 , —C(═O)OR 53 , —C(═O)N(R 54 )R 53 , —OC(═O)N(R 54 )R 53 , —N(R 54 )C(═O)R 52 , —N(R 54 )C(═O)N(R 54 )R 53 and —N(R 54 )C(═O)OR 53 ; wherein

R 52 is in each case independently selected from R 53 , (C 2-8 )alkenyl and (C 2-8 )alkynyl,

R 53 is in each case independently selected from (C 1-8 )alkyl, (C 3-8 )cycloalkyl, (C 5-14 )spirocycloalkyl, (C 3-8 )cycloalkyl-(C 1-6 )alkyl-, aryl, aryl-(C 1-6 )alkyl-, Het, and Het-(C 1-6 )alkyl-, and

R 54 is in each case independently selected from H and (C 1-3 )alkyl;

wherein each of R 52 and R 53 is optionally substituted with 1 to 3 substituents each independently selected from R 55 , halo, —CN, —OR 56 , —SR 56 , —SOR 56 , —SO 2 R 56 , —N(R 54 )R 56 , —N(R 54 )C(═O)R 55 , —N(R 54 )C(═O)N(R 54 )R 56 , —N(R 54 )C(═O)OR 56 , —OC(═O)N(R 54 )R 56 , —C(═O)R 55 , —C(═O)OR 56 , and —CON(R 54 )R 56 , wherein

R 55 is in each case independently selected from R 56 , (C 2-8 )alkenyl and (C 2-8 )alkynyl, and

R 56 is in each case independently selected from H, (C 1-8 )alkyl, (C 3-8 )cycloalkyl, (C 3-8 )cycloalkyl-(C 1-6 )alkyl-, aryl, aryl-(C 1-6 )alkyl-, Het, and Het-(C 1-6 )alkyl-,

wherein each of R 55 and R 56 is, where possible, in each case independently optionally substituted with 1 to 3 substituents each independently selected from (C 1-6 )alkyl, (C 1-6 )haloalkyl, halo, —OH, —O(C 1-6 )alkyl, —NH 2 , —NH(C 1-6 )alkyl, —N((C 1-6 )alkyl) 2 and —NH(C═O)(C 1-6 )alkyl;

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;

or a salt thereof.

10. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, having the formula:

wherein R 3 and R 5 are defined as:

R 3

R 5

11. A pharmaceutical composition comprising a compound of formula (I) according to any one of claims 1 to 10 , or a pharmaceutically acceptable salt thereof; and one or more pharmaceutically acceptable carriers.

12. A method of treating HIV infection which comprises administering to a host infected by HIV a therapeutically effective amount of a compound of formula (I) according to any one of claims 1 to 10 , or a pharmaceutically acceptable salt thereof.