Beta-lactamase inhibitor compounds

1. A compound according to Formula (I):

or a pharmaceutically acceptable salt thereof; wherein:

R 1 is —C(O)NR 7 R 8 , —CN, phenyl, a 5-6 membered heteroaryl (containing at least one heteroatom selected from nitrogen, sulfur, and oxygen), —C(O)NR′NR′C(O)R 9 , —C(O)NR′OR 10 , or a C 1 -C 6 alkyl group, wherein the alkyl group is substituted with one to three groups selected from halo, C 1 -C 3 alkoxy, —OH, —CN, —NR 7 R 8 , —NR 7 COR 9 , a 5-6 membered heteroaryl (containing at least one heteroatom selected from nitrogen, sulfur, and oxygen), and a 5-7 membered monocyclic saturated or partially saturated non-aromatic heterocyclyl (containing at least one heteroatom selected from nitrogen, sulfur, and oxygen), and wherein the phenyl and heteroaryl represented by R 1 are optionally and independently substituted with 1-3 groups selected from halo, —OH, C 1 -C 3 alkoxy, —CN, —NR 7 R 8 , and —CONR 7 R 8 ;

R 2 and R 3 are independently selected from hydrogen, halo, C 1 -C 3 alkyl, and C 3 -C 6 cycloalkyl;

R 4 and R 5 are independently selected from hydrogen, halo, —CN, —CO 2 R 9 , C 1 -C 3 alkyl, and C 1 -C 3 haloalkyl;

R 6 is hydrogen, C 1 -C 12 alkyl, C 1 -C 4 alkyl-C 1 -C 3 alkoxy-(NR′C 1 -C 6 alkyl)-C 1 -C 3 alkoxy, C 1 -C 4 alkyl-C 1 -C 3 alkoxy-C 1 -C 3 alkoxy, C 2 -C 12 alkenyl, C 3 -C 10 cycloalkyl, a 5-6 membered heteroaryl (containing at least one heteroatom selected from nitrogen, sulfur, and oxygen), and a 5-7 membered monocyclic saturated or partially saturated non-aromatic heterocyclyl (containing at least one heteroatom selected from nitrogen, sulfur, and oxygen), wherein the alkyl, alkenyl, cycloalkyl, heteroaryl and heterocyclyl are optionally and independently substituted with 1-6 groups selected from a carboxyl, halo, C 1 -C 6 alkoxy, C 1 -C 6 alkyl and phenyl;

each R 7 and R 8 are independently hydrogen, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, phenyl, C 3 -C 6 cycloalkyl, 4-7 membered monocyclic saturated or partially saturated non-aromatic heterocyclyl (containing at least one heteroatom selected from nitrogen, sulfur, and oxygen), or 5-6 membered heteroaryl (containing at least one heteroatom selected from nitrogen, sulfur, and oxygen), wherein the alkyl, alkoxy, phenyl, cycloalkyl, heterocyclyl or heteroaryl represented by R 7 or R 8 is optionally and independently substituted with 1-6 groups selected from a 5-6 membered monocyclic saturated or partially saturated non-aromatic heterocyclyl (containing at least one heteroatom selected from nitrogen, sulfur, and oxygen) optionally substituted with one or two —F atoms, carboxyl or —CO(OC 1-6 alkyl), 5-6 membered heteroaryl (containing at least one heteroatom selected from nitrogen, sulfur, and oxygen), —CN, —OH, C 1 -C 3 alkyl optionally substituted with —NH 2 or —OH, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, C 1 -C 3 alkoxy —NHCO(C 1 -C 3 alkyl), —NHCO(C 1 -C 3 alkoxy), —S(O) 2 NR′R″, —NHS(O) 2 NR′R″, —NHS(O) 2 (C 1 -C 3 alkyl), —NR′R″, and —C(O)NR′R″;

each R 9 is C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy or C 1 -C 6 alkoxy;

each R 10 is a C 1 -C 3 alkyl optionally substituted with 1-6 groups selected from a 5-6 membered monocyclic saturated or partially saturated non-aromatic heterocyclyl (containing at least one heteroatom selected from nitrogen, sulfur, and oxygen) optionally substituted with one or two —F atoms, carboxyl or —CO(OC 1-6 alkyl), a C 3 -C 6 cycloalkyl, a 5-6 membered heteroaryl (containing at least one heteroatom selected from nitrogen, sulfur, and oxygen), —CN, —OH, —NHCO(C 1 -C 3 alkyl), —NHCO(C 1 -C 3 alkoxy), —S(O) 2 NR′R″, —NHS(O) 2 NR′R″, —NHS(O) 2 (C 1 -C 3 alkyl), —NR′R″, or —C(O)NR′R″; and

each R′ and R″ is independently hydrogen, methyl, ethyl or propyl; or R′ and R″ are taken together with the nitrogen to which they are attached to form a 5-6 membered monocyclic saturated or partially saturated non-aromatic heterocyclyl (containing at least one heteroatom selected from nitrogen, sulfur, and oxygen);

provided that at least one of R 2 and R 3 is other than hydrogen.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 6 is C 1 -C 12 alkyl, C 1 -C 4 alkyl-C 1 -C 3 alkoxy-(NR′C 1 -C 6 alkyl)-C 1 -C 3 alkoxy, C 1 -C 4 alkyl-C 1 -C 3 alkoxy-C 1 -C 3 alkoxy, C 2 -C 12 alkenyl, C 3 -C 10 cycloalkyl, a 5-6 membered heteroaryl (containing at least one heteroatom selected from nitrogen, sulfur, and oxygen), and a 5-7 membered monocyclic saturated or partially saturated non-aromatic heterocyclyl (containing at least one heteroatom selected from nitrogen, sulfur, and oxygen), wherein the alkyl, alkenyl, cycloalkyl, heteroaryl and heterocyclyl are optionally and independently substituted with 1-6 groups selected from a carboxyl, halo, C 1 -C 6 alkoxy, C 1 -C 6 alkyl and phenyl.

3. The compound of claim 2 , according to formula (III):

or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 2 or a pharmaceutically acceptable salt thereof, wherein R 3 is C 1 -C 3 alkyl.

5. The compound according to claim 4 or a pharmaceutically acceptable salt thereof, wherein R 3 is methyl.

6. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 is —C(O)NR 7 R 8 .

7. The compound of claim 6 or a pharmaceutically acceptable salt thereof, wherein R 7 and R 8 are both hydrogen.

8. The compound of claim 3 , according to formula (V):

or a pharmaceutically acceptable salt thereof.

9. The compound of claim 8 or a pharmaceutically acceptable salt thereof, wherein R 6 is C 1 -C 12 alkyl.

10. The compound of claim 9 or a pharmaceutically acceptable salt thereof, wherein R 6 is ethyl, isopropyl, 2-butyl or isopentyl.

11. The compound of claim 10 or a pharmaceutically acceptable salt thereof, wherein R 6 is isopropyl.

12. The compound according to claim 9 or a pharmaceutically acceptable salt thereof, wherein R 4 and R 5 are independently H, methyl or fluoro.

13. The compound according to claim 12 or a pharmaceutically acceptable salt thereof, wherein one of R 4 and R 5 is hydrogen, and the other is fluoro.

14. The compound according to claim 12 or a pharmaceutically acceptable salt thereof, wherein R 4 is fluoro and R 5 is hydrogen.

15. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof, as claimed in claim 1 , and at least one pharmaceutically acceptable carrier, diluent or excipient.

16. The pharmaceutical composition according to claim 15 , further comprising a beta-lactam antibiotic.

17. The pharmaceutical composition according to claim 16 , wherein the beta-lactam antibiotic is cefpodoxime proxetil.

18. A method for treating a bacterial infection in a subject in need thereof, comprising administering to the subject an effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a beta-lactam antibiotic.

19. The method of claim 18 , wherein said beta-lactam antibiotic is cefpodoxime proxetil.

20. The method of claim 18 , wherein the bacterial infection is selected from the group consisting of complicated urinary tract infection, uncomplicated urinary tract infection, kidney infection, lower respiratory tract infection, hospital-acquired bacterial pneumonia (HAP), pneumonia, acute bacterial prostatitis, acute bacterial skin and soft tissue infection, sepsis, intra-abdominal infection, and diabetic foot infection.

21. A compound of the formula:

or a pharmaceutically acceptable salt thereof.

22. A method for treating a bacterial infection in a subject in need thereof, comprising administering to the subject an effective amount of a compound of the formula:

or a pharmaceutically acceptable salt thereof, and a beta-lactam antibiotic.

23. The method of claim 22 , wherein said beta-lactam antibiotic is cefpodoxime proxetil.

24. The compound of claim 1 , wherein the compound is of the formula:

or a pharmaceutically acceptable salt thereof.

25. A pharmaceutical composition comprising the compound of claim 21 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier, diluent or excipient.