Inhibitors of metallo-beta-lactamases

1. A compound of Formula I, or a pharmaceutically acceptable salt or solvate thereof, as shown below:

wherein

R 1 is selected from hydrogen or; (1-4C)alkyl, wherein each (1-4C)alkyl is optionally substituted by one or more substituent groups selected from oxo, halo, cyano, nitro, hydroxy, carboxy, NR 1A R 1B or (1-4C)alkoxy, wherein R 1A and R 1B are each independently selected from hydrogen or (1-2C)alkyl;

R 2 is selected from:

i) —C(O)OH;

ii) —C(O)OR 2A , wherein R 2A is selected from (1-6C)alkyl, (3-8C)cycloalkyl, (3-8C)cycloalkyl(1-2C)alkyl, aryl, aryl-(1-2C)alkyl, heteroaryl, heteroaryl-(1-2C)alkyl, heterocyclyl or heterocyclyl-(1-2C)alkyl, each of which is optionally substituted by one or more substituent groups R A ;

iii) —C(O)NR 2B R 2C ; wherein R 2B and R 2C are each independently selected from hydrogen, (1-6C)alkyl, (3-8C)cycloalkyl, (3-8C)cycloalkyl(1-2C)alkyl, aryl, aryl-(1-2C)alkyl, heteroaryl, heteroaryl-(1-2C)alkyl, heterocyclyl or heterocyclyl-(1-2C)alkyl, each of which is optionally substituted by one or more substituent groups R A ;

iv) —C(O)NR 2D NR 2B R 2E ; wherein R 2D is selected from hydrogen or (1-6C)alkyl and R 2B and R 2C are as defined above;

v) tetrazolyl;

vi) triazolyl;

vii) —B(OR 2F )(OR 2G ), wherein R 2F and R 2G are each independently selected from hydrogen, (1-6C)alkyl or R 2F and R 2G are linked such that, together with the B and O atoms, they form a 5 or 6-membered heterocyclic ring, which is optionally substituted by (1-2C)alkyl;

viii) trifluoromethylketone; or

ix) cyano;

x) —[C(O)] v S(NR 2X )(O)NR 2B R 2C (where v is 0 or 1), wherein R 2X is selected from hydrogen, (1-6C)alkyl, C(O)R X , C(O)OR X , aryl, aryl-(1-2C)alkyl, heteroaryl, heteroaryl-(1-2C)alkyl, heterocyclyl or heterocyclyl-(1-2C)alkyl, wherein R X is selected from (1-6C)alkyl, aryl or heteroaryl, each of which is optionally substituted with one or more R A , and wherein R 2B and R 2C are as defined above;

xi) —[C(O)] w N(R 2B )S(NR 2X )(O)R X (where w is 0 or 1), wherein R 2B , R 2X and R X are each as defined above; or

xii) —S(O) y NR 2B R 2C (wherein y is 1 or 2), and wherein R 2B and R 2C are as defined above,

and wherein R A is selected from oxo, halo, cyano, nitro or a group of the formula:

—Y 2 —X 2 —Z 2

wherein

Y 2 is absent or a linker group of the formula —[CR A1 R A2 ] m — in which m is an integer selected from 1, 2, 3 or 4, and R A1 and R A2 are each independently selected from hydrogen or (1-2C)alkyl;

X 2 is absent or —O—, —C(O)—, —C(O)O—, —OC(O)—, —CH(OR A3 )—, —N(R A3 )—, —N(R A3 )—C(O)—, —N(R A3 )—C(O)O—, —C(O)—N(R A3 )—, —N(R A3 )C(O)N(R A3 )—, —S—, —SO—, —SO 2 —, —S(O) 2 N(R A3 )—, or —N(R A3 )SO 2 — wherein R A3 is selected from hydrogen or methyl; and

Z 2 is hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, aryl, (3-6C)cycloalkyl, (3-6C)cycloalkenyl, heteroaryl or heterocyclyl;

and wherein Z 2 is optionally further substituted by one or more substituent groups independently selected from oxo, halo, cyano, nitro, hydroxy, carboxy, NR A4 R A5 , (1-4C)alkoxy, (1-4C)alkyl, (3-8C)cycloalkyl, (3-8C)cycloalkyl-(1-3C)alkyl, (1-4C)alkanoyl, (1-4C)alkylsulphonyl, aryl, aryloxy, heterocyclyl, heterocyclyloxy, heterocyclyl-(1-2C)alkyl, heteroaryl, heteroaryloxy, heteroaryl-(1-2C)alkyl, C(O)NR A4 R A5 , NR A4 C(O)R A5 , NR A4 S(O) 2 R A5 and S(O) 2 NR A4 R A5 ; wherein R A4 and R A5 are each independently selected from hydrogen, (1-4C)alkyl or (3-6C)cycloalkyl or (3-6C)cycloalkyl(1-2C)alkyl; or R A4 and R A5 can be linked such that, together with the nitrogen atom to which they are attached, they form a 4-6 membered heterocyclic ring;

and wherein any alkyl, aryl, heterocyclyl or heteroaryl group present in a substituent group on Z 2 is optionally further substituted by halo, cyano, nitro, hydroxy, caboxy, NR A6 R A7 , (1-2C)alkoxy, or (1-2C)alkyl; wherein R A6 and R A7 are selected from hydrogen or (1-2C)alkyl;

R 3 is selected from halo, cyano, hydroxyl, aryl, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (3-8C)cycloalkyl, (3-8C)cycloalkenyl, heteroaryl or heterocyclyl, wherein said aryl, (3-8C)cycloalkyl, (3-8C)cycloalkenyl, heteroaryl or heterocyclyl is optionally substituted by one or more R B ;

R B is halo, cyano, nitro, hydroxy or a group:

—Y 3 —X 3 —Z 3

wherein

Y 3 is absent or a linker group of the formula —[CR B1 R B2 ] n — in which n is an integer selected from 1, 2, 3 or 4, and R B1 and R B2 are each independently selected from hydrogen or (1-2C)alkyl;

X 3 is absent or —O—, —C(O)—, —C(O)O—, —OC(O)—, —CH(OR B3 )—, —N(R B3 )—, —N(R B4 )—C(O)—, —N(R B4 )—C(O)O—, —C(O)—N(R B3 )—, —N(R B4 )C(O)N(R B3 )—, —S—, —SO—, —SO 2 —, or —N(R B4 )SO 2 — wherein R B3 and R B4 are each independently selected from hydrogen or methyl; and

Z 3 is hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, aryl, (3-6C)cycloalkyl, (3-6C)cycloalkenyl, heteroaryl or heterocyclyl;

and wherein Z 3 is optionally further substituted by one or more substituent groups independently selected from oxo, halo, cyano, nitro, hydroxy, carboxy, NR B5 R B6 , (1-4C)alkoxy, (1-4C)alkyl, (3-8C)cycloalkyl, (3-8C)cycloalkyl-(1-3C)alkyl, (1-4C)alkanoyl, (1-4C)alkylsulphonyl, aryl, aryloxy, aryl-(1-2C)alkyl, heterocyclyl, heterocyclyloxy, heterocyclyl-(1-2C)alkyl, heteroaryl, heteroaryloxy, heteroaryl-(1-2C)alkyl, C(O)NR B5 R B6 , NR B5 C(O)R B6 , NR B5 S(O) 2 R B6 and S(O) 2 NR B5 R B6 ; wherein R B5 and R B6 are each independently selected from hydrogen, (1-4C)alkyl or (3-6C)cycloalkyl or (3-6C)cycloalkyl(1-2C)alkyl; or R B5 and R B6 can be linked such that, together with the nitrogen atom to which they are attached, they form a 4-7 membered heterocyclic ring;

and wherein any alkyl, aryl, heterocyclyl or heteroaryl group present in a substituent group on Z 3 is optionally further substituted by halo, cyano, nitro, hydroxy, caboxy, NR B7 R B8 , (1-2C)alkoxy, or (1-2C)alkyl; wherein R B7 and R B8 are selected from hydrogen or (1-2C)alkyl;

or R B3 and Z 3 can be linked such that, together with the nitrogen atom to which they are attached, they form a 4-7 membered heterocyclic ring, which is optionally substituted by oxo, halo, cyano, nitro, hydroxy, carboxy, NR B5 R B6 , (1-4C)alkoxy, (1-4C)alkyl, (3-8C)cycloalkyl, (3-8C)cycloalkyl-(1-3C)alkyl, (1-4C)alkanoyl, (1-4C)alkylsulphonyl, C(O)NR B5 R B6 , NR B5 C(O)R B6 , NR B5 S(O) 2 R B6 and S(O) 2 NR B5 R B6 ;

X 1 is selected from N or C—R 4 ;

R 4 is selected from halo, cyano, nitro, hydroxy or a group

—Y 4 —X 4 —Z 4

wherein:

Y 4 is absent or a linker group of the formula —[CR 4A R 4B ] n — in which q is an integer selected from 1 or 2 and R 4A and R 4B are each independently selected from hydrogen or methyl;

X 4 is absent or —O—, —C(O)—, —C(O)O—, —OC(O)—, —CH(OR 4C )—, —N(R 4C )—, —N(R 4D )—C(O)—, —N(R 4D )—C(O)O—, —C(O)—N(R 4C )—, —S—, —SO—, —SO 2 —, —S(O) 2 N(R 4C )—, or —N(R 4D )SO 2 — wherein R 4C and R 4D are each independently selected from hydrogen or (1-4C)alkyl; and

Z 4 is hydrogen or (1-4C)alkyl which is optionally further substituted by one or more substituent groups independently selected from oxo, halo, cyano, nitro, hydroxy, carboxy, NR 4E R 4F or (1-2C)alkoxy; wherein R 4E and R 4F are each independently selected from hydrogen or (1-2C)alkyl;

R 5 is selected from hydrogen, halo, cyano, nitro, hydroxy or a group of the formula:

—Y 5 —X 5 -Q 5 -Z 5

wherein Y 5 is absent or a linker group of the formula —[CR 5A R 5B ] p — in which p is an integer selected from 1 or 2, and R 5A and R 5B are each independently selected from hydrogen or (1-2C)alkyl;

X 5 is absent or —O—, —C(O)—, —C(O)O—, —OC(O)—, —CH(OR 5C )—, —N(R 5C )—, N(R 5D )—C(O)—, —N(R 5D )—C(O)O—, —C(O)—N(R 5C )—, —N(R 5D )C(O)N(R 5C )—, —S—, —SO—, —SO 2 —, —S(O) 2 N(R 5C )—, or —N(R 5D )SO 2 — wherein R 5C and R 5D are each independently selected from hydrogen or (1-6C)alkyl;

Q 5 is absent or a (1-4C)alkylene optionally interrupted with one or more 0 or S atoms; and

Z 5 is hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, aryl, (3-6C)cycloalkyl, (3-6C)cycloalkenyl, heteroaryl or heterocyclyl;

and wherein Z 5 is optionally further substituted by one or more substituent groups independently selected from oxo, halo, cyano, nitro, hydroxy, carboxy, NR 5E R 5F (1-4C)alkoxy, (1-4C)alkyl, (1-4C)haloalkyl, (1-4C)haloalkoxy, (3-8C)cycloalkyl, (3-8C)cycloalkyl-(1-3C)alkyl, (1-4C)alkanoyl, (1-4C)alkyl sulphonyl, aryl, aryloxy, aryl-(1-2C)alkyl, heterocyclyl, heterocyclyloxy, heterocyclyl-(1-2C)alkyl, heteroaryl, heteroaryloxy, heteroaryl-(1-2C)alkyl, Si[(1-4C)alkyl] 3 , C(O)R 5E , C(O)OR 5E , OC(O)R 5E , C(O)NR 5E R 5F , NR 5E C(O)R 5F , NR 5E S(O) 2 R 5F and S(O) 2 NR 5E R 5F ; wherein R 5E and R 5F are each independently selected from hydrogen, (1-4C)alkyl, (1-4C)haloalkyl, (3-6C)cycloalkyl or (3-6C)cycloalkyl(1-2C)alkyl; or R 5E and R 5F can be linked such that, together with the nitrogen atom to which they are attached, they form a 4-7 membered heterocyclic ring;

and wherein any alkyl, aryl, heterocyclyl or heteroaryl group present in a substituent group on Z 5 is optionally further substituted by one or more substituent groups selected from halo, (1-2C)haloalkyl, cyano, nitro, hydroxy, carboxy, NR 5G R 5H , (1-2C)alkoxy, or (1-2C)alkyl; wherein R 5G and R 5H are selected from hydrogen or (1-2C)alkyl;

or R 5C and Z 5 can be linked such that, together with the nitrogen atom to which they are attached, they form a 4-7 membered heterocyclic ring, which is optionally substituted by oxo, halo, cyano, nitro, hydroxy, carboxy, NR 5E R 5F , (1-4C)alkoxy, (1-4C)alkyl, (1-4C)haloalkyl, (3-8C)cycloalkyl, (3-8C)cycloalkyl-(1-3C)alkyl, (1-4C)alkanoyl, (1-4C)alkylsulphonyl, C(O)R 5E , C(O)OR 5E , OC(O)R 5E , C(O)NR 5E R 5F , NR 5E C(O)R 5F , NR 5E S(O) 2 R 5F and S(O) 2 NR 5E R 5F .

2. A compound of Formula I according to claim 1 , or a pharmaceutically acceptable salt or solvate thereof, for use in the treatment of a bacterial infection in combination with a beta-lactam antibiotic.

3. A compound according to claim 1 , wherein R 1 is selected from hydrogen or (1-4C)alkyl which is optionally substituted by one or more substituent groups selected from oxo, halo, or (1-2C)alkoxy.

4. A compound according to claim 1 , wherein R 1 is hydrogen.

5. A compound according to claim 1 , wherein R 2 is selected from:

(i) —C(O)OH;

(ii) —C(O)NR 2B R 2C ; wherein R 2B and R 2C are each independently selected from hydrogen, (1-6C)alkyl, (3-8C)cycloalkyl, aryl or heteroaryl, each of which is optionally substituted by one or more substituent groups R A ;

(iii) —C(O)NR 2D NR 2B R 2C ; wherein R 2D is selected from hydrogen or (1-2C)alkyl and R 2B and R 2C are as defined above;

(iv) tetrazolyl;

(v) —B(OR 2F )(OR 2G ), wherein R 2F and R 2G are each independently selected from hydrogen, (1-4C)alkyl or R 2F and R 2G are linked such that, together with the B and O atoms, they form a 5 or 6-membered heterocyclic ring, which is optionally substituted by (1-2C)alkyl; or

(vi) cyano:

and wherein R A is selected from halo, cyano, or a group of the formula:

—X 2 —Z 2

wherein

X 2 is absent or —C(O)—, —SO 2 —; and

Z 2 is hydrogen, (1-6C)alkyl, aryl, or heteroaryl;

and wherein Z 2 is optionally further substituted by one or more substituent groups independently selected from halo, hydroxy, NR A4 R A5 , (1-4C)alkoxy or (1-4C)alkyl, wherein R A4 and R A5 are each independently selected from hydrogen, or (1-2C)alkyl.

6. A compound according to claim 1 , wherein R 2 is —C(O)OH, —C(O)NH 2 , tetrazolyl or cyano.

7. A compound according to claim 1 , wherein R 3 is selected from halo, cyano, hydroxy, aryl, (1-6C)alkyl, (2-6C)alkenyl, heteroaryl or heterocyclyl, wherein said aryl, heteroaryl or heterocyclyl is optionally substituted by one or more R B ;

R B is halo, cyano, nitro, hydroxy or a group:

—Y 3 —X 3 —Z 3

wherein

Y 3 is absent or a linker group of the formula —[CR B1 R B2 ] n — in which n is an integer selected from 1, 2, 3 or 4, and R B1 and R B2 are each independently selected from hydrogen or (1-2C)alkyl;

X 3 is absent or —O—, —C(O)—, —C(O)O—, —OC(O)—, —CH(OR B3 )—, —N(R B3 )—, N(R B4 )—C(O)—, —N(R B4 )—C(O)O—, —C(O)—N(R B3 )—, —N(R B4 )C(O)N(R B3 )—, —S—, —SO—, —SO 2 —, or —N(R B4 )SO 2 — wherein R B3 and R B4 are each independently selected from hydrogen or methyl; and

Z 3 is hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, aryl, (3-6C)cycloalkyl, (3-6C)cycloalkenyl, heteroaryl or heterocyclyl;

and wherein Z 3 is optionally further substituted by one or more substituent groups independently selected from oxo, halo, cyano, nitro, hydroxy, carboxy, NR B5 R B6 , (1-4C)alkoxy, (1-4C)alkyl, (1-4C)alkanoyl, (1-4C)alkylsulphonyl, C(O)NR B5 R B6 , NR B5 C(O)R B6 , NR B5 S(O) 2 R B6 and S(O) 2 NR B5 R B6 ; wherein R B5 and R B6 are each independently selected from hydrogen, (1-4C)alkyl or (3-6C)cycloalkyl or (3-6C)cycloalkyl(1-2C)alkyl.

8. A compound according to claim 1 , wherein R 3 is selected from halo, aryl or 5- or 6-membered heteroaryl, wherein said aryl or heteroaryl is optionally substituted by one or more R B ;

R B is halo, cyano, nitro, hydroxy or a group:

—Y 3 —X 3 —Z 3

wherein

Y 3 is absent or a linker group of the formula —[CR B1 R B2 ] n — in which n is an integer selected from 1 or 2, and R B1 and R B2 are each independently selected from hydrogen or methyl;

X 3 is absent or —O—, —C(O)—, —C(O)O—, —N(R B3 )—, —C(O)—N(R B3 )—, —S—, —SO—, or —SO 2 —, wherein R B3 and R B4 are each independently selected from hydrogen or methyl; and

Z 3 is hydrogen, (1-6C)alkyl, aryl or 5- or 6-membered heteroaryl;

and wherein Z 3 is optionally further substituted by one or more substituent groups independently selected from oxo, halo, cyano, nitro, hydroxy, carboxy, amino, (1-2C)alkoxy or (1-2C)alkyl.

9. A compound according to claim 1 , wherein X 1 is C—R 4 .

10. A compound according to claim 1 , wherein R 4 is selected from halo, cyano, nitro, hydroxy or a group

—Y 4 —X 4 —Z 4

wherein:

Y 4 is absent or a linker group of the formula —[CR 4A R 4B ] q — in which q is an integer selected from 1 or 2 and R 4A and R 4B are each independently selected from hydrogen or methyl;

X 4 is absent or —O—, —C(O)—, —C(O)O—, —OC(O)—, —N(R 4C )—, —N(R 4D )—C(O)—, —C(O)—N(R 4C )—, —S—, —SO— or —SO 2 —, wherein R 4C and R 4D are each independently selected from hydrogen or (1-4C)alkyl; and

Z 4 is hydrogen or (1-4C)alkyl which is optionally further substituted by one or more substituent groups independently selected from oxo, halo, cyano, nitro, hydroxy, carboxy, amino or (1-2C)alkoxy.

11. A compound according to claim 1 , wherein R 4 is selected from halo or (1-4C)alkyl.

12. A compound according to claim 1 , wherein R 5 is selected from hydrogen, halo, cyano, nitro, hydroxy or a group of the formula:

—Y 5 —X 5 -Q 5 -Z 5

wherein

Y 5 is absent or a linker group of the formula —[CR 5A R 5B ] p — in which p is an integer selected from 1 or 2, and R 5A and R 5B are each independently selected from hydrogen or (1-2C)alkyl;

X 5 is absent or —O—, —C(O)—, —C(O)O—, —OC(O)—, —N(R 5C )—, —N(R 5D )—C(O)—, —C(O)—N(R 5C )—, —S—, —SO—, —SO 2 —, —S(O) 2 N(R 5C )—, or —N(R 5D )SO 2 — wherein R 5C and R 5D are each independently selected from hydrogen or (1-6C)alkyl;

Q 5 is absent or a (1-3C)alkylene optionally interrupted with one or more 0 atoms; and

Z 5 is hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, aryl, (3-6C)cycloalkyl, (3-6C)cycloalkenyl, heteroaryl or heterocyclyl;

and wherein Z 5 is optionally further substituted by one or more substituent groups independently selected from oxo, halo, cyano, nitro, hydroxy, carboxy, NR 5E R 5F , (1-4C)alkoxy, (1-4C)alkyl, (1-4C)haloalkyl, (1-4C)haloalkoxy, (3-8C)cycloalkyl, (3-8C)cycloalkyl-(1-3C)alkyl, (1-4C)alkanoyl, (1-4C)alkyl sulphonyl, aryl, aryloxy, aryl-(1-2C)alkyl, heterocyclyl, heterocyclyloxy, heterocyclyl-(1-2C)alkyl, heteroaryl, heteroaryloxy, heteroaryl-(1-2C)alkyl, Si[(1-4C)alkyl] 3 , C(O)R 5E , C(O)OR 5E , OC(O)R 5E , C(O)NR 5E R 5F , NR 5E C(O)R 5F , NR 5E S(O) 2 R 5F and S(O) 2 NR 5E R 5F ; wherein R 5E and R 5F are each independently selected from hydrogen, (1-4C)alkyl, (1-4C)haloalkyl or (3-6C)cycloalkyl; or R 5E and R 5F can be linked such that, together with the nitrogen atom to which they are attached, they form a 4-7 membered heterocyclic ring;

and wherein any alkyl, aryl, heterocyclyl or heteroaryl group present in a substituent group on Z 5 is optionally further substituted by halo, cyano, nitro, hydroxy, caboxy, NR 5G R 5H , (1-2C)alkoxy, or (1-2C)alkyl; wherein R 5G and R 5H are selected from hydrogen or (1-2C)alkyl;

or R 5C and Z 5 can be linked such that, together with the nitrogen atom to which they are attached, they form a 4-7 membered heterocyclic ring, which is optionally substituted by one or more substituent groups selected from oxo, halo, (1-2C)haloalkyl, cyano, nitro, hydroxy, carboxy, NR 5E R 5F , (1-4C)alkoxy, (1-4C)alkyl, (1-4C)haloalkyl, (3-8C)cycloalkyl, (1-4C)alkanoyl, (1-4C)alkyl sulphonyl, C(O)R 5E , C(O)OR 5E , C(O)NR 5E R 5F or NR 5E C(O)R 5F ; or

R 4 and R 5 may be linked such that, together with the carbon atoms to which they are attached, they form a fused 5, 6, 7 or 8-membered non-aromatic carbocyclic or heterocyclic ring, which is optionally substituted by one or more substituents selected from oxo, halo, cyano, nitro, hydroxy, carboxy, NR 5I R 5J , (1-4C)alkoxy, (1-4C)alkyl, (1-4C)haloalkyl, (3-8C)cycloalkyl, (1-4C)alkanoyl, (1-4C)alkylsulphonyl, C(O)R 5J , C(O)OR 5J , OC(O)R 5J , C(O)NR 5I R 5J , NR 5I C(O)R 5J , NR 5I S(O) 2 R 5J and S(O) 2 NR 5I R 5J , wherein R 5i and R 5j are each independently selected from hydrogen, (1-4C)alkyl or (3-6C)cycloalkyl.

13. A compound according to claim 1 , wherein R 5 is selected from hydrogen, halo, cyano, nitro, hydroxy or a group

—X 5 —Z 5

wherein

X 5 is absent or —N(R 5C )—, —S(O) 2 N(R 5C )— or —N(R 5D )SO 2 — wherein R 5C is selected from hydrogen or (1-2C)alkyl; and

Z 5 is hydrogen, (1-6C)alkyl, aryl, 5- or 6-membered heteroaryl or 5- or 6-membered heterocyclyl;

and wherein Z 5 is optionally further substituted by one or more substituent groups independently selected from halo, cyano, nitro, hydroxy, carboxy, NR 5E R 5F , (1-4C)alkoxy, (1-4C)alkyl, (1-4C)haloalkyl, (1-4C)haloalkoxy, ((1-4C)alkylsulphonyl, aryl, 5- or 6-membered heterocyclyl, 5- or 6-membered heteroaryl, C(O)R 5E , C(O)OR 5E , C(O)NR 5E R 5F or NR 5E C(O)R 5F ; wherein R 5E and R 5F are each independently selected from hydrogen, (1-4C)alkyl or (1-4C)haloalkyl;

and wherein any alkyl, aryl, heterocyclyl or heteroaryl group present in a substituent group on Z 5 is optionally further substituted by halo, cyano, nitro, hydroxy, amino, (1-2C)alkoxy or (1-2C)alkyl; or

R 4 and R 5 may be linked such that, together with the carbon atoms to which they are attached, they form a fused 5, 6, 7 or 8-membered non-aromatic carbocyclic or heterocyclic ring, which is optionally substituted by one or more substituents selected from oxo, halo, cyano, nitro, hydroxy, carboxy, NR 5I R 5J , (1-4C)alkoxy, (1-4C)alkyl or (1-4C)haloalkyl, wherein R 5i and R 5j are each independently selected from hydrogen or (1-4C)alkyl.

14. A compound according to claim 1 , wherein R 5 is selected from hydrogen, halo, cyano, nitro, hydroxy or a group

—X 5 —Z 5

wherein

X 5 is absent or —N(R 5C )—, —S(O) 2 N(R 5C )— or —N(R 5D )SO 2 — wherein R 5C is selected from hydrogen or (1-2C)alkyl; and

Z 5 is hydrogen, (1-6C)alkyl, aryl, 5- or 6-membered heteroaryl or 5- or 6-membered heterocyclyl;

and wherein Z 5 is optionally further substituted by one or more substituent groups independently selected from halo, cyano, hydroxy, carboxy, amino, (1-2C)alkoxy, (1-2C)alkyl, (1-2C)haloalkyl, (1-2C)haloalkoxy, (1-2C)alkylsulphonyl, phenyl, C(O)R 5E , C(O)OR 5E , C(O)NR 5E R 5F or NR 5E C(O)R 5F ; wherein R 5E and R 5F are each independently selected from hydrogen, (1-2C)alkyl or (1-2C)haloalkyl;

and wherein any alkyl or phenyl group present in a substituent group on Z 5 is optionally further substituted by halo, cyano, hydroxy, amino, (1-2C)alkoxy or (1-2C)alkyl.

15. A compound selected from any one of the following:

3-Phenyl-4,5,6,7-tetrahydro-1H-indole-2-carboxylic acid;

7-Methyl-3-phenyl-4,5,6,7-tetrahydro-1H-indole-2-carboxylic acid;

7,7-Dimethyl-3-phenyl-4,5,6,7-tetrahydro-1H-indole-2-carboxylic acid;

3,5,5-Trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-2-carboxylic acid;

3-(3,5-Dichlorophenyl)-5,5-dimethyl-4,5,6,7-tetrahydro-1H-4,6-methanoindole-2-carboxylic acid;

3-(3,5-Dichlorophenyl)-4-methyl-5-phenyl-1H-pyrrole-2-carboxylic acid;

5-(5-(3,5-Dichlorophenyl)furan-2-yl)-4-methyl-1H-pyrrole-2-carboxylic acid;

3-(3-Chloro-4-((methylsulfonyl)methyl)phenyl)-4-ethyl-5-(2-(trifluoromethyl)phenyl)-1H-pyrrole-2-carboxylic acid;

3-(3,5-Dichlorophenyl)-4-methyl-5-phenyl-1H-pyrrole-2-carboxamide;

3-(3,5-Dichlorophenyl)-4-methyl-5-phenyl-1H-pyrrole-2-carbonitrile;

5-(3-(3,5-Dichlorophenyl)-4-methyl-5-phenyl-1H-pyrrol-2-yl)-1H-tetrazole;

3-(3,5-Dichlorophenyl)-4-ethyl-5-phenyl-1H-pyrrole-2-carboxylic acid;

4-Ethyl-3-(4-fluorophenyl)-5-phenyl-1H-pyrrole-2-carboxylic acid;

3-(3-Chloro-4-((methylsulfonyl)methyl)phenyl)-4-ethyl-5-phenyl-1H-pyrrole-2-carboxylic acid;

4-Methyl-3-phenyl-5-(3-(2,2,2-trifluoroacetyl)phenyl)-1H-pyrrole-2-carboxylic acid;

3-(3,5-Dichlorophenyl)-4-methyl-5-(2-(2,2,2-trifluoroacetyl)phenyl)-1H-pyrrole-2-carboxylic acid;

3-(3,5-Dichlorophenyl)-4-methyl-5-(3-(2,2,2-trifluoroacetyl)phenyl)-1H-pyrrole-2-carboxylic acid;

3-(3,5-Dichlorophenyl)-4-methyl-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrole-2-carboxylic acid;

3-(3,5-Dichlorophenyl)-4-fluoro-5-phenyl-1H-pyrrole-2-carboxylic acid;

3-(3,5-Dichlorophenyl)-5-(thiophen-2-yl)-1H-pyrrole-2-carboxylic acid;

3-(4-Fluorophenyl)-5-(phenylsulfonamido)-1H-pyrrole-2-carboxylic acid;

5-(Diisopropylamino)-3-(4-fluorophenyl)-1H-pyrrole-2-carboxylic acid;

3-(4-Hydroxyphenyl)-4-methyl-5-phenyl-1H-pyrrole-2-carboxylic acid;

3-(4-Mercaptophenyl)-4-methyl-5-phenyl-1H-pyrrole-2-carboxylic acid;

3-(4-(Carboxymethyl)phenyl)-4-methyl-5-phenyl-1H-pyrrole-2-carboxylic acid;

3-(4-((N,N-Dimethylsulfamoyl)methyl)phenyl)-4-methyl-5-phenyl-1H-pyrrole-2-carboxylic acid;

5-Cyclopropyl-3-(3,5-dichlorophenyl)-4-methyl-1H-pyrrole-2-carboxylic acid;

4-Methyl-5-nitro-3-phenyl-1H-pyrrole-2-carboxylic acid;

5-Acetyl-4-methyl-3-phenyl-1H-pyrrole-2-carboxylic acid;

5-Acetyl-1,4-dimethyl-3-phenyl-1H-pyrrole-2-carboxylic acid;

4-Methyl-3-phenyl-5-(3-(2,2,2-trifluoro-1-hydroxyethyl)phenyl)-1H-pyrrole-2-carboxylic acid;

4-Methyl-3-phenyl-5-(2-(2,2,2-trifluoro-1-hydroxyethyl)phenyl)-1H-pyrrole-2-carboxylic acid;

3-Chloro-5-(2-phenoxyacetamido)-1H-pyrrole-2-carboxylic acid;

5-(2-Phenoxyacetamido)-3-phenyl-1H-pyrrole-2-carboxylic acid;

3-(4-Carboxyphenyl)-4-methyl-5-phenyl-1H-pyrrole-2-carboxylic acid; or

2,4-Bis(4-fluorophenyl)-1H-imidazole-5-carboxylic.

16. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt or solvate thereof, in admixture with a pharmaceutically acceptable diluent or carrier.

17. A pharmaceutical composition according to claim 16 , for use in the treatment of a bacterial infection in combination with a beta-lactam antibiotic.

18. A method of treating a bacterial infection in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition thereof in administration with a pharmaceutically acceptable diluent or carrier, in combination with a beta-lactam antibiotic.

19. A kit of parts comprising the following components:

(i) a compound of Formula I, according to claim 1 , or a pharmaceutically-acceptable salt thereof, in association with a pharmaceutically acceptable adjuvant, diluent or carrier; and

(ii) a β-lactam antibiotic, or a pharmaceutically-acceptable salt thereof, in association with a pharmaceutically acceptable adjuvant, diluent or carrier,

wherein the components are provided in a form which is suitable for sequential, separate and/or simultaneous administration.

20. A kit according to claim 19 , for use in the treatment of a bacterial infection.