Pyrimidine derivatives and their use in the treatment of cancer and further diseases

1. A compound of Formula (I), or a pharmaceutically acceptable salt thereof:

wherein:

X represents —CH 2 —, —NR 8 —, —O— or —S(O) n —;

R 1 represents C 1-6 alkyl, C 2-6 alkoxy, C 1-6 alkoxyC 1-6 alkyl, hydroxyC 1-6 alkyl, hydroxyC 1-6 alkoxy or hydroxyC 1-6 alkoxyC 1-6 alkyl;

R 2 represents hydrogen, C 1-6 alkyl or phenyl wherein said phenyl is optionally substituted with 1, 2 or 3 substituents selected from R 6 ;

R 3 represents C 1-6 alkyl, C 1-6 alkoxy or —S—C 1-6 alkyl;

R 4 represents hydrogen, halogen, C 1-6 alkyl or C 1-6 alkoxy;

L 1 represents a direct bond, —(CR 9 R 10 ) m —, —CH═CH—(CR 9 R 10 ) q —, —C≡C—(CR 9 R 10 ) q —, —O—(CR 9 R 10 ) q —, —C(O)—O—(CR 9 R 10 ) q — or —O—(CH 2 ) q —NR—(CH 2 ) q —;

R 5 represents —NR 11 R 12 , C 3-6 cycloalkyl, phenyl or a monocyclic 4, 5, 6 or 7 membered heterocyclic ring which comprises 1, 2 or 3 heteroatoms independently selected from O, N or S wherein said phenyl and heterocyclic rings are optionally substituted with 1, 2 or 3 substituents selected from R 7 ;

R 6 represents C 1-6 alkyl, fluoroC 1-6 alkyl, C 1-6 alkoxy, hydroxy, halogen, cyano, —S(O) n —C 1-6 alkyl or —CH 2 —C(O)—O—C 1-6 alkyl;

R 7 represents C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxyC 1-6 alkyl, hydroxy, hydroxyC 1-6 alkyl or —(CH 2 ) q —NR 11 R 12 ;

R 8 represents hydrogen or C 1-6 alkyl;

R 9 and R 10 independently represent hydrogen or methyl;

R 11 and R 12 independently represent hydrogen, C 1-4 alkyl or C 1-4 alkoxyC 2-4 alkyl;

m represents 1, 2, 3, 4, 5 or 6;

n represents 0, 1 or 2; and

q represents 0, 1, 2, 3, 4, 5 or 6.

2. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein X represents —CH 2 —.

3. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 represents C 1-6 alkyl.

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

5. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 represents phenyl wherein said phenyl is optionally substituted with 1, 2 or 3 substituents selected from R 6 .

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

7. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 represents C 1-6 alkoxy.

8. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 represents hydrogen.

9. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is bonded at the ortho position of the phenyl ring relative to linkage —X—.

10. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein q represents 1, 2 or 3.

11. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein q represents 2 or 3.

12. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein L 1 represents —(CR 9 R 10 ) m —, —CH═CH—(CR 9 R 10 ) q — or —C≡C—(CR 9 R 10 ) q —.

13. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein L 1 represents —O—(CR 9 R 10 ) q —.

14. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein L 1 is bonded at the para position of the phenyl ring relative to linkage —X—.

15. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein L 1 is bonded at the meta position of the phenyl ring relative to linkage —X—.

16. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein L 1 is bonded at the ortho position of the phenyl ring relative to linkage —X—.

17. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 represents NR 11 R 12 or a monocyclic 4, 5, 6 or 7 membered heterocyclic ring which comprises 1, 2 or 3 heteroatoms independently selected from O, N or S wherein said heterocyclic ring is optionally substituted with 1, 2 or 3 substituents selected from R 7 .

18. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 represents NR 11 R 12 and R 11 and R 12 both represent methyl.

19. A pharmaceutical composition which comprises a compound according to any one of claims 1 to 18 , or a pharmaceutically acceptable salt thereof, in association with a pharmaceutically acceptable diluent or carrier.

20. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 represents —NR 11 R 12 , C 3-6 cycloalkyl, phenyl or a monocyclic 4, 5, 6 or 7 membered heterocyclic ring which comprises 1, 2 or 3 heteroatoms independently selected from O, N or S wherein said phenyl and heterocyclic rings are optionally substituted with 1, 2 or 3 substituents selected from R 7 .

21. A compound according to claim 12 , or a pharmaceutically acceptable salt thereof, wherein R 5 represents NR 11 R 12 or a monocyclic 4, 5, 6 or 7 membered heterocyclic ring which comprises 1, 2 or 3 heteroatoms independently selected from O, N or S wherein said heterocyclic ring is optionally substituted with 1, 2 or 3 substituents selected from R 7 .

22. A compound according to claim 13 , or a pharmaceutically acceptable salt thereof, wherein R 5 represents NR 11 R 12 or a monocyclic 4, 5, 6 or 7 membered heterocyclic ring which comprises 1, 2 or 3 heteroatoms independently selected from O, N or S wherein said heterocyclic ring is optionally substituted with 1, 2 or 3 substituents selected from R 7 .

23. A compound according to claim 1 , or a pharmaceutically acceptable salt, wherein the compound is:

5-(4-(2-(Dimethylamino)ethoxy)benzyl)-6-methyl-N 4 -pentylpyrimidine-2,4-diamine;

5-(4-(3-(Dimethylamino)propoxy)benzyl)-6-methyl-N 4 -pentylpyrimidine-2,4-diamine;

6-Methyl-N 4 -pentyl-5-(4-(2-(piperidin-1-yl)ethoxy)benzyl)pyrimidine-2,4-diamine;

6-Methyl-N 4 -pentyl-5-(4-(2-(pyrrolidin-1-yl)ethoxy)benzyl)pyrimidine-2,4-diamine;

5-(4-(2-(Benzyl(methyl)amino)ethoxy)benzyl)-6-methyl-N 4 -pentyl-pyrimidine-2,4-diamine;

6-Methyl-N 4 -pentyl-5-(4-(3-(pyrrolidin-1-yl)propoxy)benzyl)pyrimidine-2,4-diamine;

6-Methyl-5-(4-(3-(4-methylpiperazin-1-yl)propoxy)benzyl)-N 4 -pentylpyrimidine-2,4-diamine;

5-(4-(3-(Dimethylamino)propoxy)-2-methoxybenzyl)-6-methyl-N 4 -pentylpyrimidine-2,4-diamine;

(S)-4-(Dimethylamino)butyl 4-((2-amino-4-(1-hydroxypentan-2-yl-amino)-6-methylpyrimidin-5-yl)methyl)-3-methoxybenzoate;

5-(2-(3-(Dimethylamino)propoxy)benzyl)-6-methyl-N 4 -pentyl-pyrimidine-2,4-diamine;

5-(3-(3-(Dimethylamino)propoxy)benzyl)-6-methyl-N 4 -pentyl-pyrimidine-2,4-diamine;

6-Methyl-N 4 -pentyl-5-(3-(2-(piperidin-1-yl)ethoxy)benzyl)pyrimidine-2,4-diamine;

5-(3-(2-(Dimethylamino)ethoxy)benzyl)-6-methyl-N 4 -pentylpyrimidine-2,4-diamine;

6-Methyl-N 4 -pentyl-5-(3-(2-(pyrrolidin-1-yl)ethoxy)benzyl)pyrimidine-2,4-diamine;

5-(3-((Dimethylamino)methyl)benzyl)-6-methyl-N 4 -pentylpyrimidine-2,4-diamine;

5-(4-(3-(Dimethylamino)prop-1-ynyl)benzyl)-6-methyl-N 4 -pentyl-pyrimidine-2,4-diamine;

5-(4-(3-(Dimethylamino)propyl)benzyl)-6-methyl- N 4 -pentylpyrimidine-2,4-diamine;

5-(3-(3-(Dimethylamino)propyl)benzyl)-6-methyl- N 4 -pentylpyrimidine-2,4-diamine;

5-(4-(3-(Dimethylamino)propoxy)-2-methylbenzyl)-6-methyl- N 4 -pentylpyrimidine-2,4-diamine;

(R)-Methyl2-(3-(1-(2-amino-5-(4-(3-(dimethylamino)propoxy)-2-methoxybenzyl)-6-methylpyrimidin-4-ylamino)-3-hydroxypropyl)phenyl)acetate;

5-(2-Methoxy-4-(3-morpholinopropoxy)benzyl)-6-methyl- N 4 -pentylpyrimidine-2,4-diamine;

5-(2-Methoxy-4-(3-(4-methylpiperazin-1-yl)propoxy)benzyl)-6-methyl- N 4 -pentylpyrimidine-2,4-diamine; or

5-(4-(4-(Dimethylamino)butyl)-2-methoxybenzyl)-6-methyl-N 4 -pentylpyrimidine-2,4-diamine.

24. A pharmaceutical composition comprising a compound according to claim 23 , or a pharmaceutically acceptable salt thereof, in association with a pharmaceutically acceptable diluent or carrier.