Inhibitors of protein kinases

1. A compound of general Formula I:

or a pharmaceutically acceptable salt or polymorph thereof, including all tautomers and stereoisomers thereof wherein:

A is N and B is CH, C(C 1-4 alkyl) or C(NH 2 ),

R a is H or methyl;

R 1 is selected from the group consisting of:

C 1-8 alkyl; —NR 6 R 7 , C 1-6 alkyl-NR 6 R 7 , R 20 , —C 1-6 alkyl-R 20 , —C 1-6 alkyl-C(O)OR 4 , C 1-6 alkyl-C(O)R 4 , —NR 10 —(C 1-6 alkyl)-NR 6 R 7 , —NR 10 —(C 1-6 alkyl)-R 20 , —NR 10 —(C 1-6 alkyl)-C(O)OR 4 , —NR 10 R 20 , O—(C 1-6 alkyl)-NR 6 R 7 , —O—(C 1-6 alkyl)-R 20 , —O—(C 1-6 alkyl)-C(O)OR 4 , —OR 20 , C 1-6 alkyl-OR 20 , C 1-6 alkyl-SR 20 , C 1 -C 6 alklyl-NR 10 R 20 , (C 1-6 alkyl)-O—(C 1-6 alkyl)-R 20 , (C 1-6 alkyl)-S—(C 1-6 alkyl)-R 20 , C(O)R 20 ;

where alkyl moieties may be straight or branched and may be substituted by one or more substituents chosen from halo, methoxy, ethoxy NR 6 R 7 or a nitrogen-containing heterocyclic ring;

R 4 represents H or C 1-4 -alkyl;

R 6 and R 7 are each independently selected from the group consisting of H, C 1-6 alkyl, hydroxy-C 2-6 alkyl-;

R 10 represents H or C 1-4 alkyl;

R 20 is selected from aryl, heteroaryl, carbocyclyl and heterocyclyl and may be substituted by one or more substituents selected from:

C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl any of which may be substituted by one or more halo or OH substituents;

R 21 , —C 1-4 alkyl-R 21 ; OR 21 , O(C 1-4 alkyl)R 12 , SR 21 , SOR 21 , SO 2 R 21 , C(O)R 21 , C 1-4 alkyl-OR 21 ,

—O(C 2-6 alkenyl), —O(C 2-6 alkynyl), any of which may be substituted by one or more halo or OH substituents;

OR 22 , SR 22 —SR 22 , —SO 2 R 2 , —C(O)R 22 , —C(O)OR 22 , —C 1-4 alkyl-O—R 22 , —C 1-4 alkyl-O—C 1-4 alkyl-O—R 2 , C 1-4 alkyl-C(O)R 22 , —C 1-4 alkyl-C(O)R 2 , NR 11 C(O)OR 22 , NR 11 C(O)R 22 , —SO 2 —NR 11 R 12 , —C(O)—NR 11 R 12 , —C 1-4 alkyl-C(O)—NR 11 R 12 , —NH—SO 2 R 15 , —N(C 1-4 alkyl)-SO 2 R 15 , —(C 1-4 alkyl)NR 11 R 12 , NR 11 R 12 , —(C 1-6 alkyl)NR 11 R 12 , nitro, halogen, cyano and hydroxyl; and when R 20 is carbocyclyl or heterocyclyl or an aromatic group in which an aromatic ring is fused to a non-aromatic ring, R 20 may additionally be substituted by oxo;

R 21 is selected from aryl, heteroaryl, carbocyclyl and heterocyclyl and may be substituted by one or more substituents as defined below;

when R 21 is an aryl or heteroaryl group, it may be substituted by one or more substituents selected from: wherein phenyl is optionally substituted by methyl, methoxy, halogen, halomethyl fluoromethoxy or trifluoromethoxy;

when R 21 is a carbocyclic or heterocyclic group it may be substituted by one or more substituents selected from methyl, oxo or halogen;

R 22 is hydrogen or C 1-6 alkyl optionally substituted by halo or hydroxyl;

R 11 and R 12 each independently represent a substituent selected from H or C 1-4 alkyl or R 11 and R 12 are joined such that together they form a 3-8 membered non-aromatic ring;

R 15 represents H or C 1-4 alkyl;

R 2 represents H or NH 2 ;

each R 3 independently represents a substituent selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-8 cycloalkyl (optionally substituted by methyl, oxo or halogen), phenyl (optionally substituted by methyl, methoxy, halogen, halomethyl fluoromethoxy or trifluoromethoxy), —C 1-6 alkyl-OH, —C 1-4 alkylphenyl (optionally substituted by methyl, methoxy, halogen, halomethyl fluoromethoxy or trifluoromethoxy), C 1-6 alkoxy-, C 1-6 alkenyloxy, C 3-4 alkynyloxy-, C 1-6 haloalkoxy-, —O—C 3-8 cycloalkyl, —O—C 1-4 alkyl-C 3-8 cycloalkyl, —O-phenyl (optionally substituted by methyl, methoxy, halogen, halomethyl fluoromethoxy or trifluoromethoxy), —O—C 1-4 alkylphenyl (optionally substituted by methyl, methoxy, halogen, halomethyl fluoromethoxy or trifluoromethoxy), —S(C 1-6 alkyl), —SO(C 1-6 alkyl), —SO 2 C 1-6 alkyl, —SO 2 C 3-8 cycloalkyl, —SO 2 —NR 31 R 32 , —C(O)C 1-6 alkyl, —C(O)C 3-8 cycloalkyl, —C(O)OH, —C(O)OC 1-6 alkyl, —C(O)—NR 31 R 32 , —C 1-4 alkyl-O—C 1-4 alkyl, —C 1-4 alkyl-O—C 1-4 alkyl-OH, —C 1-4 alkyl-O—C 1-4 alkyl-O—C 1-4 alkyl, —C 1-4 alkyl-O—C 3-7 cycloalkyl, —C 1-4 alkyl-C(O)C 1-6 alkyl, —C 1-4 alkyl-C(O)OH, —C 1-4 alkyl-C(O)OC 1-4 alkyl, —C 1-4 alkyl-C(O)—NR 31 R 32 , —NH—SO 2 R 33 , —N(C 1-4 alkyl)-SO 2 R 3 , —(C 1-4 alkyl)NR 31 R 32 , —NR 31 R 32 , —(C 1-6 alkyl)NR 31 R 32 , nitro, halogen, cyano, hydroxyl;

R 31 and R 32 each independently represent a substituent selected from H, C 1-4 alkyl or C 1-4 haloalkyl or R 31 and R 32 are joined such that together they form a 3-8 membered non-aromatic ring;

R 33 represents H or C 1-4 alkyl;

x represents the number of independently selected R 3 substituents on the phenyl ring, in the range 1-2.

2. The compound of claim 1 wherein:

A is N and B is CH, C(C 1-4 alkyl) or C(NH 2 ),

R 1 is selected from the group consisting of:

C 1-8 alkyl;

C 1-8 haloalkyl;

aryl;

heteroaryl;

C 3-12 carbocyclyl;

heterocyclyl;

—C 1-6 alkyl-aryl;

—C 1-6 alkyl-heteroaryl;

—C 1-6 alkyl-carbocyclyl;

—C 1-6 alkyl-heterocyclyl;

—C 1-6 alkyl-C(O)OH;

—C 1-6 alkyl-C(O)OC 1-4 alkyl;

—NR 10 C 1-6 alkyl-aryl;

—NR 10 C 1-6 alkyl-heteroaryl;

—NR 10 C 1-6 alkyl-carbocyclyl;

—NR 10 C 1-6 alkyl-heterocyclyl;

—NR 10 C 1-6 alkyl-C(O)OH;

—NR 10 C 1-6 alkyl-C(O)OC 1-4 alkyl;

—NR 10 aryl;

—NR 10 heteroaryl;

—NR 10 carbocyclyl;

—NR 10 heterocyclyl;

—OC 1-6 alkyl-aryl;

—OC 1-6 alkyl-heteroaryl;

—OC 1-6 alkyl-carbocyclyl;

—OC 1-6 alkyl-heterocyclyl;

—OC 1-6 alkyl-C(O)OH;

—OC 1-6 alkyl-C(O)OC 1-4 alkyl;

—Oaryl;

—Oheteroaryl;

—Ocarbocyclyl; and

—Oheterocyclyl;

wherein any of the aforesaid aryl and heteroaryl may optionally be substituted by one or more groups independently selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 4-6 haloalkyl, C 3-8 cycloalkyl (optionally substituted by methyl, oxo or halogen), phenyl (optionally substituted by methyl, methoxy, halogen, halomethyl fluoromethoxy or trifluoromethoxy)-C 1-6 alkyl-OH, —C 1-4 alkylphenyl (wherein phenyl is optionally substituted by methyl, methoxy, halogen, halomethyl fluoromethoxy or trifluoromethoxy), C 1-6 alkoxy-, C 1-6 alkenyloxy, C 3-6 alkynyloxy-, C 1-6 haloalkoxy-, —O—C 3-8 cycloalkyl, —O—C 1-4 alkyl-C 3-8 cycloalkyl, —O-phenyl (optionally substituted by methyl, methoxy, halogen, halomethyl fluoromethoxy or trifluoromethoxy), —O—C 1-4 alkylphenyl (optionally substituted by methyl, methoxy, halogen, halomethyl fluoromethoxy or trifluoromethoxy), —S(C 1-6 alkyl), —SO(C 1-6 alkyl), —SO 2 C 1-6 alkyl, —SO 2 C 3-8 cycloalkyl, —SO 2 —NR 11 R 12 , —C(O)C 1-6 alkyl, —C(O)C 3-8 cycloalkyl, —C(O)OH, —C(O)OC 11 alkyl, —C(O)—NR 11 R 12 , —C 1-4 alkyl-O—C 1-4 alkyl, —C 1-4 alkyl-O—C 1-4 alkyl-OH, —C 1-4 alkyl-O—C 1-4 alkyl-O—C 1-4 alkyl, —C 1-4 alkyl-O—C 3-7 cycloalkyl, —C 1-4 alkyl-C(O)C 1-6 alkyl, —C 1-4 alkyl-C(O)OH, —C 1-4 alkyl-C(O)OC 1-4 alkyl, —C 1-4 alkyl-C(O)—NR 11 R 12 , —NH—SO 2 R 15 , —N(C 1-4 alkyl)-SO 2 R 15 , —(C 1-4 alkyl)NR 11 R 12 , NR 11 R 12 , —(C 1-6 alkyl)NR 11 R 12 , nitro, halogen, cyano and hydroxyl; and

wherein any of the aforesaid carbocyclyl and heterocyclyl may optionally be substituted by one or more groups independently selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-8 cycloalkyl (optionally substituted by methyl, oxo or halogen), phenyl (optionally substituted by methyl, methoxy, halogen, halomethyl fluoromethoxy or trifluoromethoxy), —C 1-6 alkyl-OH, —C 1-4 alkylphenyl (wherein phenyl is optionally substituted by methyl, methoxy, halogen, halomethyl fluoromethoxy or trifluoromethoxy), C 1-6 alkoxy-, C 1-6 alkenyloxy, C 3-6 alkynyloxy-, C 1-6 haloalkoxy-, —O—C 3-8 cycloalkyl, —O—C 1-4 alkyl-C 3-8 cycloalkyl, —O-phenyl (optionally substituted by methyl, methoxy, halogen, halomethyl fluoromethoxy or trifluoromethoxy), —O—C 1-4 alkylphenyl (optionally substituted by methyl, methoxy, halogen, halomethyl fluoromethoxy or trifluoromethoxy), —S(C 1-6 alkyl), —SO(C 1-6 alkyl), —SO 2 C 1-6 alkyl, —SO 2 C 3-8 cycloalkyl, —SO 2 —NR 11 R 12 , —C(O)C 1-6 alkyl, —C(O)C 3-8 cycloalkyl, —C(O)OH, —C(O)OC 1-6 alkyl, —C(O)—NR 11 R 12 , —C 1-4 alkyl-O—C 1-4 alkyl, —C 1-4 alkyl-O—C 1-4 alkyl-OH, —C 1-4 alkyl-O—C 1-4 alkyl-O—C 1-4 ally-O—C 1-4 alkyl, —C 1-4 alkyl-O—C 3-7 cycloalkyl, —C 1-4 alkyl-C(O)C 1-6 alkyl, —C 1-4 alkyl-C(O)OH, —C 1-4 alkyl-C(O)OC 1-4 alkyl, —C 1-4 alkyl-C(O)—NR 11 R 12 , —NH—SO 2 R 15 , —N(C 1-4 alkyl)-SO 2 R 15 , —(C 1-4 alkyl)NR 11 R 12 , —NR 11 R 12 , —(C 1-6 alkyl)NR 11 R 12 , nitro, halogen, cyano, hydroxyl and oxo;

R 2 represents H or NH 2 ;

R 3 represents a substituent, selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-8 cycloalkyl (optionally substituted by methyl, oxo or halogen), phenyl (optionally substituted by methyl, methoxy, halogen, halomethyl fluoromethoxy or trifluoromethoxy), —C 1-6 alkyl-OH, —C 1-4 alkylphenyl (optionally substituted by methyl, methoxy, halogen, halomethyl fluoromethoxy or trifluoromethoxy), C 1-6 alkoxy-, C 1-16 alkenyloxy, C 1-6 alkynyloxy-, C 1-6 haloalkoxy-, —O—C 3-8 cycloalkyl, —O—C 1-4 alkyl-C 3-8 cycloalkyl, —O-phenyl (optionally substituted by methyl, methoxy, halogen, halomethyl fluoromethoxy or trifluoromethoxy), —O—C 1-4 alkylphenyl (optionally substituted by methyl, methoxy, halogen, halomethyl fluoromethoxy or trifluoromethoxy), —S(C 1-6 alkyl), —SO(C 1-6 alkyl), —SO 2 C 1-6 alkyl, —SO 2 C 3-8 cycloalkyl, —SO 2 —NR 31 R 32 , —C(O)C 1-6 alkyl, —C(O)C 3-8 cycloalkyl, —C(O)OH, —C(O)OC 1-6 alkyl, —C(O)—NR 31 R 32 , —C 1-4 alkyl-O—C 1-4 alkyl, —C 1-4 alkyl-O—C 1-6 alkyl-OH, —C 1-4 alkyl-O—C 1-4 alkyl-O—C 1-4 alkyl, —C 1-4 alkyl-O—C 3-7 cycloalkyl, —C 1-4 alkyl-C(O)C 1-6 alkyl, —C 1-4 alkyl-C(O)OH, —C 1-4 alkyl-C(O)OC 1-4 alkyl, —C 1-4 alkyl-C(O)—NR 31 R 32 , —NH—SO 2 R 33 , —N(C 1-4 alkyl)-SO 2 R 33 , —(C 1-4 alkyl)NR 31 R 32 , —NR 31 R 32 , —(C 1-6 alkyl)NR 31 R 32 , nitro, halogen, cyano, hydroxyl;

R 4 and R 5 independently represent H or C 1-4 -alkyl;

R 6 and R 7 are each independently selected from the group consisting of H, C 1-6 alkyl, hydroxy-C 2-6 alkyl-;

R 10 represents H or C 1-4 alkyl;

R 11 and R 12 each independently represent a substituent selected from H or C 1-4 alkyl or R 11 and R 12 are joined such that together they form a 3-8 membered non-aromatic ring;

R 15 represents H or C 1-4 alkyl;

R 31 and R 32 each independently represent a substituent selected from H, C 1-4 alkyl or C 1-4 haloalkyl or R 31 and R 32 are joined such that together they form a 3-8 membered non-aromatic ring;

R 33 represents H or C 1-14 alkyl;

x represents the number of independently selected R 3 substituents on the phenyl ring, in the range 1-2;

m represents an integer 1-4; and

n represents an integer 2-4.

3. The compound of claim 1 wherein, independently or in any combination:

R a is hydrogen;

B is CH or C 1-4 alkyl;

R 2 is hydrogen,

R 3 is halogen, C 1-6 alkoxy, —O—C 1-4 alkylphenyl (e.g. —O-benzyl) or —O—C 1-4 alkyl-C 3-8 cycloalkyl;

and

x is 1 or 2.

4. The compound of claim 3 wherein, independently or in any combination:

B is CH;

R 2 is hydrogen; and

R 3 is halogen, methoxy, ethoxy, isopropyloxy, benzyloxy or —OCH 2 cyclopropyl.

5. The compound of claim 3 wherein x is 1 and R 3 represents C 1-6 alkoxy, —O—C 1-4 alkylphenyl or —O—C 1-4 alkyl-C 3-8 cycloalkyl.

6. A compound of general Formula I:

or a pharmaceutically acceptable salt or polymorph thereof, including all tautomers and stereoisomers thereof wherein:

A is N and B is CH or C 1-4 alkyl,

R a is H;

R 1 is selected from the group consisting of:

C 1-8 alkyl; —NR 6 R 7 , C 1-6 alkyl-NR 6 R 7 , R 20 , —C 1-6 alkyl-R 20 , —C 1-6 alkyl-C(O)OR 4 , C 1-6 alkyl-C(O)R 4 , —NR 10 —(C 1-6 alkyl)-NR 6 R 7 , —NR 10 —(C 1-6 alkyl)-R 20 , —NR 10 —(C 1-6 alkyl)-C(O)OR 4 , —NR 10 R 20 , O—(C 1-6 alkyl)-NR 6 R 7 , —O—(C 1-6 alkyl)-R 20 , —O—(C 1-6 alkyl)-C(O)OR 4 , —OR 20 , C 1-6 alkyl-OR 20 , C 1-6 alkyl-SR 20 , C 1 -C 6 alkyl-NR 10 R 20 , (C 1-6 alkyl)-O—(C 1-6 alkyl)-R 20 , C 1-6 alkyl)-S—(C 1-6 alkyl)-R 20 , C(O)R 20 ;

where alkyl moieties may be straight or branched and may be substituted by one or more substituents chosen from halo, methoxy, ethoxy NR 6 R 7 or a nitrogen-containing heterocyclic ring;

R 4 represents H or C 1-4 -alkyl;

R 6 and R 7 are each independently selected from the group consisting of H, C 1-6 alkyl, hydroxy-C 2-6 alkyl-;

R 10 represents H or C-alkyl;

R 20 is selected from aryl, heteroaryl, carbocyclyl and heterocyclyl and may be substituted by one or more substituents selected from:

C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl any of which may be substituted by one or more halo or OH substituents;

R 21 , —C 1-4 alkyl-R 21 ; OR 21 , O(C 1-4 alkyl)R 21 , SR 21 , SOR 21 , SO 2 R 21 , C(O)R 21 , C 1-4 alkyl-OR 21 ,

—O(C 2-6 alkenyl), —O(C 2-6 alkynyl), any of which may be substituted by one or more halo or OH substituents;

OR 22 —SR 22 —SOR 22 —SO 2 R 22 , —C(O)R 2 , —C(O)OR 22 , —C 1-4 alkyl-O—R 2 , —C 1-4 alkyl-O—C 1-4 alkyl-O—R 22 , C 1-4 alkyl-C(O)R 22 , —C 1-4 alkyl-C(O)R 22 , NR 11 C(O)OR 22 , NR 11 C(O)R 22 , —SO 2 —NR 11 R 12 —C(O)—NR 11 R 12 , —C 1-4 alkyl-C(O)—NR 11 R 12 —NH—SO 2 R 15 , —N(C 1-4 alkyl)-SO 2 R 15 , —(C 1-4 alkyl)NR 11 R 12 , NR 11 NR 12 , —(C 1-6 alkyl)NR 11 R 12 , nitro, halogen, cyano and hydroxyl; and when R 20 is carbocyclyl or heterocyclyl or an aromatic group in which an aromatic ring is fused to a non-aromatic ring, R 20 may additionally be substituted by oxo;

R 21 is selected from aryl, heteroaryl, carbocyclyl and heterocyclyl and may be substituted by one or more substituents as defined below;

when R 21 is an aryl or heteroaryl group, it may be substituted by one or more substituents selected from: wherein phenyl is optionally substituted by methyl, methoxy, halogen, halomethyl fluoromethoxy or trifluoromethoxy;

when R 21 is a carbocyclic or heterocyclic group it may be substituted by one or more substituents selected from methyl, oxo or halogen;

R 22 is hydrogen or C 1-6 alkyl optionally substituted by halo or hydroxyl;

R 11 and R 12 each independently represent a substituent selected from H or C 1-4 alkyl or R 11 and R 12 are joined such that together they form a 3-8 membered non-aromatic ring;

R 15 represents H or C-alkyl:

R 2 represents H or C 1-4 alkyl;

x is 2 and one of the R 3 groups is methoxy, ethoxy, -isopropyloxy, benzyloxy or (1-cyclopropyl)methoxy, and the other R 3 group is halo.

7. The compound of claim 6 wherein R 1 is:

—C 1 -C 6 alkyl;

—R 20 ;

—C(O)R 20 ;

—C 1 -C 6 alkyl-R 20 ,

wherein the alkyl group is optionally substituted with halo, methoxy, ethoxy, —NR 6 R 7 or a nitrogen-containing heterocyclyl ring;

—C 1 -C 6 alkyl-OR 20 ;

—(C 1 -C 6 alkyl)-O—(C 1 -C 6 alkyl)-R 20 ;

—C 1 -C 6 alkyl-NR 10 R 20 ;

—C 1 -C 6 alkyl-SR 20 ;

—NR 10 R 20 ;

—NR 6 R 7 ;

—NR 10 —(C 1 -C 6 alkyl)-NR 6 R 7 or

—NR 10 —(C 1-6 alkyl)-C(O)OH.

8. The compound of claim 7 , wherein R 1 represents R 20 or NR 10 R 20 and R 20 is a substituted or unsubstituted carbocyclyl, heterocyclyl, aryl or heteroaryl group.

9. The compound of claim 7 , wherein R 1 is a substituted carbocyclyl group wherein the substitutent is on the same atom which links the carbocyclyl group to the remainder of the molecule.

10. The compound of claim 7 wherein R 1 represents C(O)R 20 and R 20 is an aryl or heteroaryl group, which may be unsubstituted or substituted, or a heterocyclyl group.

11. The compound of claim 10 , wherein R 20 is phenyl or a 6-membered heterocyclyl group.

12. The compound of claim 7 , wherein R 1 represents C 1 -C 6 alkyl-R 20 and R 20 is an aryl, heteroaryl or heterocyclyl group, any of which may optionally be substituted.

13. The compound of claim 7 wherein R 1 represents C 1 -C 6 alkyl-OR 20 , —(C 1 -C 6 alkyl)-O—(C 1 -C 6 alkyl)-R 20 , C 1 -C 6 alkyl-NR 10 R 20 or C 1 -C 6 alkyl-SR 20 and R 20 is an aryl or heteroaryl group optionally substituted.

14. The compound of claim 1 wherein R 20 is a 5- or 6-membered heterocyclyl ring containing one or two heteroatoms independently selected from oxygen, sulfur or nitrogen.

15. The compound of claim 14 , wherein R 20 is a piperidinyl, pyrrolidinyl, tetrahydropyranyl or tetrahydrothiopyranyl ring.

16. The compound of claim wherein the heterocyclyl ring R 20 is unsubstituted or substituted by one or more substituents independently selected from oxo, —C 1-4 alkyl, —C 1-4 alkyl-O—C 1-4 alkyl, —C(O)C 1-4 alkyl, —C(O)OC 1-4 alkyl, halogen and —C 1-4 alkylR 21 .

17. The compound of claim 1 wherein R 20 represents a cycloalkyl group which is unsubstituted or substituted by one or more —C 1-8 alkyl, oxo, —NH 2 , —NHC(O)C 1-4 alkyl, —NHC(O)OC 1-4 alkyl, —C(O)NH 2 , optionally substituted aryl or heteroaryl groups.

18. The compound of claim 1 wherein R 20 represents naphthyl or phenyl, optionally substituted with one or more substituents selected from —NH—SO 2 C 1-4 alkyl, C 1-4 alkyl, —O(C 1-4 alkyl), —NHR 12 , where R 12 is as defined above, aryl, heteroaryl, nitro and halo.

19. The compound of claim 1 wherein R 20 represents a monocyclic 5- or 6-membered heteroaryl ring system.

20. The compound of claim 1 wherein R 20 represents a bicyclic heteroaryl group comprising phenyl fused to unsaturated heterocyclyl ring or a heteroaryl moiety fused to an unsaturated ring optionally containing one or more further heteroatoms.

21. The compound of claim 19 wherein R 20 is unsubstituted or substituted with one or more substituents selected from C 1-4 alkyl, halo, —(C 1 -C 4 alkyl)-O—R 21 or R 21 , where R 21 is unsubstituted phenyl or heteroaryl.

22. The compound of claim 1 wherein R 1 is —NR 6 R 7 ; or —NR 10 —(C 1 -C 6 alkyl)-NR 6 R 7 and R 6 and R 7 are each independently hydrogen or C 1 -C 4 alkyl.

23. The compound of claim 1 wherein R 1 is —C 1 -C 6 alkyl-NR 10 R 20 ; —NR 10 R 20 ; —NR 10 —(C 1 -C 6 alkyl)-NR 6 R 7 or —NR 10 —(C 1-6 alkyl)-C(O)OH; and R 10 is hydrogen or methyl.

24. A pharmaceutical composition comprising the compound of claim 1 as active ingredient together with a pharmaceutically acceptable excipient or diluent.

25. A process for the preparation of the compound of formula (I) of claim 1 , or a protected derivative thereof, the process comprising

(a) converting one compound of formula (I) to another compound of formula (I); or

(b) reacting a compound of formula A

wherein A, B, R 1 , R a and R 2 are as defined in general formula (I) and X is a suitable substituent for a cross coupling reaction, or a protected derivative thereof with a compound of formula B

wherein R 3 and x are as defined in general formula (I) and Y is a suitable substituent for a cross coupling reaction, or a protected derivative thereof;

wherein X and Y represent suitable substituents for a cross-coupling reaction and are chosen to react with one another; or

(c) reacting a compound of formula E

or a protected derivative thereof

wherein R 1 is as defined for general formula (I) and L 4 represents a suitable leaving group;

with a compound of formula F

wherein R a , R 2 , R 3 , x, A and B are as defined in general formula (I), or a protected derivative thereof; or

(d) preparing a compound of formula (I), in which R 1 is a moiety which connects to the main carbonyl of formula (I) via a nitrogen atom

by a process comprising reaction of the corresponding amine or a protected derivative thereof

with a compound of formula G

wherein R a , R 2 , R 3 , x, A and B are as defined for general formula (I) and L 2 represents a suitable leaving group;

or a protected derivative thereof;

(e) reacting a compound of formula F as defined above or a protected derivative thereof with a compound of formula J

wherein R 1 is as defined for general formula (I);

in the presence of a suitable coupling agent; or

(f) reacting a compound of formula K

wherein R 2 , R 3 , x, A and B are as defined for general formula (I) and Z represents a suitable substituent for a cross-coupling reaction

with a compound of formula L

wherein R 1 and R a are as defined for general formula (I);

under suitable conditions for coupling reaction; or

(g) preparing a compound of formula (I), in which R 1 is —NHR 20 or —NH—(C 1-6 alkyl)-R 20 by reacting a compound of formula F as defined above with a compound of formula:

R 20 N═C═O or R 20 —(C 1-6 alkyl)-N═C═O

wherein R 2 is as defined for general formula (I), for example R 20 represents a heteroaryl group such as pyridine.

26. The compound of claim 1 which is piperidine-4-carboxylic acid [6-(2-methoxy-phenyl)-pyrimidin-4-yl]-amide.

27. The composition of claim 24 wherein the active ingredient is piperidine-4-carboxylic acid [6-(2-methoxy-phenyl)-pyrimidin-4-yl]-amide.

28. The compound as defined in claim 1 and selected from the group consisting of Example compounds 1 to 156:

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156

29. The compound as defined in claim 1 and selected from the group consisting of Example compounds 1A to 21A and 23A to 34A:

 1A

Piperidine-4-carboxylic acid [6-(2-

ethoxy-phenyl)-pyrimidin-4-yl]-amide

 2A

1-Methyl-piperidine-4-carboxylic acid

[6-(2-ethoxy-phenyl)-pyrimidin-4-yl]-amide

 3A

1-Ethyl-piperidine-4-carboxylic acid [6-

(2-ethoxy-phenyl)-pyrimidin-4-yl]-amide

 4A

1-Isopropyl-piperidine-4-carboxylic acid

[6-(2-ethoxy-phenyl)-pyrimidin-4-yl]-amide

 5A

1-Benzyl-piperidine-4-carboxylic acid

[6-(2-ethoxy-phenyl)-pyrimidin-4-yl]-amide

 6A

Piperidine-4-carboxylic acid [6-(2-

methoxy-phenyl)-pyrimidin-4-yl]-amide

 7A

Piperidine-4-carboxylic acid [6-(2-

isopropoxy-phenyl)-pyrimidin-4-yl]-amide

 8A

Piperidine-4-carboxylic acid [6-(2-

cyclopropylmethoxy-phenyl)-pyrimidin-4-yl]-amide

 9A

Piperidine-4-carboxylic acid [6-(2-

benzyloxy-phenyl)-pyrimidin-4-yl]-amide

10A

Piperidine-4-carboxylic acid [6-(4-

fluoro-2-rnethoxy-phenyl)-pyrimidin-4-yl]-amide

11A

Piperidine-4-carboxylic acid [6-(5-

fluoro-2-methoxy-phenyl)-pyrimidin-4-yl]-amide

12A

Piperidine-4-carboxylic acid [6-(2-

fluoro-6-methoxy-phenyl)-pyrimidin-4-yl]-amide

13A

1-Acetyl-piperidine-4-carboxylic acid

[6-(2-ethoxy-phenyl)-pyrimidin-4-yl]-amide

14A

Piperidine-4-carboxylic acid [6-(2-

methoxy-phenyl)-pyrimidin-4-yl]-amide

hydrochloride

15A

Piperidine-4-carboxylic acid [6-(2-

methoxy-phenyl)-pyrimidin-4-yl]-amide

mesylate

16A

Piperidine-3-carboxylic acid [6-(2-

methoxy-phenyl)-pyrimidin-4-yl]-amide

17A

(S)-Piperidine-3-carboxylic acid [6-(2-

methoxy-phenyl)-pyrimidin-4-yl]-amide

18A

(R)-Piperidine-3-carboxylic acid [6-(2-

methoxy-phenyl)-pyrimidin-4-yl]-amide

19A

1-[6-(2-Methoxy-phenyl)-pyrimidin-4-

ylcarbamoyl]-pyrrolidine-2-carboxylic

acid

20A

1-Acetyl-piperidine-3-carboxylic acid

[6-(2-methoxy-phenyl)-pyrimidin-4-yl]-amide

21A

1-Methanesulfonyl-piperidine-3-

carboxylic acid [6-(2-methoxy-phenyl)-

pyrimidin-4-yl]-amide

23A

1-[6-(2-Methoxy-phenyl)-pyrimidin-4-

yl]-3-piperidin-3-yl-urea hydrochloride

24A

1-[6-(2-Methoxy-phenyl)-pyrimidin-4-

yl]-3-piperidin-4-yl-urea hydrochloride

25A

N-[6-(2-Methoxy-phenyl)-pyrimidin-4-

yl]-2,2-dimethyl-propionamide

26A

N-[6-(2-Methoxy-phenyl)-pyrimidin-4-

yl]-2-phenyl-acetamide

27A

N-[6-(2-Methoxy-phenyl)-pyrimidin-4-

yl]-benzamide

28A

6-Oxo-piperidine-3-carboxylic acid [6-

(2-methoxy-phenyl)-pyrimidin-4-yl]-amide

29A

1-(2-Dimethylamino-ethyl)-3-[6-(2-

methoxy-phenyl)-pyrimidin-4-yl]-urea

30A

(3-{3-[6-(2-methoxy-phenyl)-pyrimidin-

4-yl]-ureido}-phenyl)-acetic acid

31A

{3-[6-(2-methoxy-phenyl)-pyrimidin-4-

yl]-ureido}-acetic acid

32A

2-{3-[6-(2-methoxy-phenyl)-pyrimidin-

4-yl]-ureido}-propionic acid

33A

2-{3-[6-(2-methoxy-phenyl)-pyrimidin-

4-yl]-ureido}-2-methyl-propionic acid

34A

{3-[6-(2-methoxy-phenyl)-pyrimidin-4-

yl]-1-methyl-ureido}-acetic acid.