N-Aryl-sulfoximine-substituted pyrimidines as CDK-and/or VEGF inhibitors, their production and use as pharmaceutical agents

1. A compound of formula (I)

in which

Q stands for phenyl,

R 1 stands for halogen, —CF 3 , C 1 -C 4 -Alkyl or Nitro,

R 2 stands for C 1 -C 10 -alkyl, C 2 -C 10 -alkenyl, C 2 -C 10 -alkinyl, C 3 -C 10 -cycloalkyl, heterocyclyl with 3 to 7 ring atoms, C n -aryl or heteroaryl with 5 to 10 ring atoms, each of which is optionally substituted in one or more places, in the same way or differently, with

(i) hydroxy, halogen, —NR 7 R 8 or with the group —COR 6 , and/or

(ii) C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 1 -C 4 -alkoxy, C 2 -C 4 -alkinyl, which is optionally substituted in one or more places, in the same way or differently, with hydroxy, halogen, —NR 7 R 8 or with the group —COR 6 ,

X stands for —O—, —S— or for the group —NH— or —NR 11 —, wherein R 11 is a C 1 -C 3 -Alkyl,

or in case X stands for the group —NR 11 —

R 2 , R 11 and X form together a heterocyclyl ring with 3 to 7 ring atoms, which optionally contains one or more additional heteroatoms and optionally is substituted in one or more places in the same way or differently, with hydroxy, C 1 -C 3 -alkyl, C 1 -C 3 -alkoxy, —NR 7 R 8 or halogen,

R 3 stands for hydroxy, halogen, —CF 3 , —OCF 3 or for the group —NR 7 R 8 , or for C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl or C 1 -C 6 -alkoxy, each of which is optionally substituted in one or more places, in the same way or differently, with halogen, hydroxy or the group —NR 7 R 8 ,

m stands for 0-4,

R 4 and R 5 in each case independently of one another, stand for C 1 -C 6 -alkyl, C 1 -C 6 -alkenyl or C 3 -C 6 -cycloalkyl, each of which is optionally substituted in one or more places, in the same way or differently, with hydroxy, halogen, C 1 -C 3 -alkoxy, C 1 -C 3 -alkylthio, cyano, C 3 -C 6 -cycloalkyl, C 1 -C 6 -hydroxyalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkinyl or with the group —CF 3 , —OCF 3 or —NR 7 R 8 ,

or

R 4 and R 5 together form a ring of the group

 V, W and Y stand for —CH 2 —, which are optionally and independently substituted in one or more places, in the same way or differently, with halogen, hydroxy, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy or —NR 7 R 8 ,

n stands for 0-4,

R 6 stands for hydrogen or C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy or C 3 -C 6 -cycloalkyl, each of which is optionally substituted in one or more places, in the same way or differently, with C 1 -C 6 -alkyl,

R 7 and R 8 in each case independently of one another, stand for hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, hydroxy-C 1 -C 6 -alkyl, dihydroxy-C 1 -C 6 -alkyl, phenyl, heteroaryl or for the group —(CH 2 ) p NR 9 R 10 ,

or

R 7 and R 8 form together with the nitrogen atom a heterocycyl ring with 3 to 7 ring atoms, which optionally contain one or more nitrogen, oxygen and/or sulfur atoms and/or can be interrupted by one or more —C(O)— groups in the ring,

R 9 and R 10 in each case independently of one another, stand for hydrogen, C 1 -C 6 -alkyl, hydroxy-C 1 -C 6 -alkyl, dihydroxy-C 1 -C 6 -alkyl and

p stands for 0-4,

or a diastereomer, enantiomer or salt thereof.

2. A compound according to claim 1 , wherein R 1 stands for halogen, —CF 3 , C 1 -C 2 -Alkyl or Nitro.

3. A compound according to claim 1 , wherein R 1 stands for bromine.

4. A compound according to claim 1 , wherein R 2 stands for C 1 -C 10 -alkyl, C 2 -C 10 -alkinyl, C 3 -C 10 -cycloalkyl, heterocyclyl with 3 to 7 ring atoms, C n -aryl or a monocyclic heteroaryl, each of which is optionally substituted in one or more places, in the same way or differently, with hydroxy and/or C 1 -C 4 -alkyl, which is optionally substituted in one or more places, in the same way or differently wth hydroxyl.

5. A Compound according to claim 1 , wherein R 2 stands for C 2 -C 6 -alkyl, C 2 -C 8 -alkinyl, C 4 -C 7 -cycloalkyl, heterocyclyl with 5 to 7 ring atoms, phenyl or a monocyclic heteroaryl with 6 ring atoms, each of which is optionally substituted in one or more places, in the same way or differently, with hydroxy and/or C 1 -C 4 -alkyl, which is optionally substituted in one or more places, in the same way or differently with hydroxyl.

6. A compound according to claim 1 , wherein R 2 stands for C 3 -C 5 -alkyl, C 3 -C 5 -alkinyl, C 5 -C 6 -cycloalkyl, heterocyclyl with 6 ring atoms, phenyl or monocyclic heteroaryl with 6 ring atoms and only one heteroatom, each of which is optionally substituted in one or more places, in the same way or differently, with hydroxy and/or C 1 -C 4 -alkyl, which is optionally substituted in one or more places, in the same way or differently with hydroxyl.

7. A compound according to claim 1 , wherein X stands for —O—, —S— or for the group —NH—.

8. A compound according to claim 1 , wherein X stands for —NH—.

9. A compound according to claim 1 , wherein m stands for 0 or 1.

10. A compound according to claim 1 , wherein

R 4 and R 5 independently stand for C 1 -C 6 -alkyl which is optionally substituted in one or more places, in the same way or differently, with hydroxy, halogen, C 1 -C 3 -alkoxy, C 1 -C 6 -hydroxyalkyl or —NR 7 R 8 or

R 4 and R 5 together form a ring of the group

 V, W and Y stand for —CH 2 —, which are optionally and independently substituted in one or more places, in the same way or differently, with halogen, hydroxy, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy or —NR 7 R 8 , and

n stands for 1-3.

11. A compound according to claim 1 , wherein

R 4 and R 5 independently stand for C 1 -C 6 -alkyl which is optionally substituted in one or more places, in the same way or differently, with hydroxyl or —NR 7 R 8 ,

or

R 4 and R 5 together form a ring of the group

 V, W and Y stand for —CH 2 —, which are optionally and independently substituted in one or more places in the same way or differently with hydroxyl or —NR 7 R 8 , and

n stands for 1-3.

12. A compound according to claim 1 , wherein in case of a NR 7 R 8 -substituent

R 7 and R 8 stand in each case independently of one another for hydrogen, C 1 -C 6 -alkyl, hydroxy-C 1 -C 6 -alkyl, dihydroxy-C 1 -C 6 -alkyl or for the group —(CH 2 ) p NR 9 R 10

or

R 7 and R 8 form together with the nitrogen atom a heterocycyl ring with 5 or 6 ring atoms which is optionally interrupted by one —C(O)— group in the ring and/or can be substituted by hydroxy, C 1 -C 6 -alkyl, hydroxy-C 1 -C 6 -alkyl or dihydroxy-C 1 -C 6 -alkyl.

13. A compound according to claim 1 , wherein

R 1 stands for halogen, —CF 3 , C 1 -C 2 -Alkyl or Nitro,

R 2 stands for C 1 -C 10 -alkyl, C 2 -C 10 -alkinyl, C 3 -C 10 -cycloalkyl, heterocyclyl with 3 to 7 ring atoms, C n -aryl or a monocyclic heteroaryl each of which is optionally substituted in one or more places, in the same way or differently, with hydroxy and/or C 1 -C 4 -alkyl, which is optionally substituted in one or more places, in the same way or differently with hydroxyl,

X stands for —O—, —S— or for the group —NH—,

m stands for 0,

R 4 and R 5 independently stand for C 1 -C 6 -alkyl which is optionally substituted in one or more places, in the same way or differently, with hydroxyl or —NR 7 R 8 ,

or

R 4 and R 5 together form a ring of the group

 V, W and Y stand for —CH 2 —, which are optionally and independently substituted in one or more places in the same way or differently with hydroxyl or —NR 7 R 8 ,

n stands for 1-3.

14. A compound according to claim 13 , wherein R 1 stands for bromine.

15. A compound according to claim 14 , wherein R 2 stands for C 2 -C 6 -alkyl, C 2 -C 8 -alkinyl, C 4 -C 7 -cycloalkyl, heterocyclyl with 5 to 7 ring atoms, phenyl or a monocyclic heteroaryl with 6 ring atoms each of which is optionally substituted in one or more places, in the same way or differently, with hydroxy and/or C 1 -C 4 -alkyl, which is optionally substituted in one or more places, in the same way or differently with hydroxyl.

16. A compound according to claim 14 , wherein R 2 stands for C 3 -C 5 -alkyl, C 3 -C 5 -alkinyl, C 5 -C 6 -cycloalkyl, heterocyclyl with 6 ring atoms, phenyl or monocyclic heteroaryl with 6 ring atoms and only one heteroatom each of which is optionally substituted in one or more places, in the same way or differently, with hydroxy and/or C 1 -C 4 -alkyl, which is optionally substituted in one or more places, in the same way or differently with hydroxyl.

17. A compound according to claim 13 , wherein X stands for —NH—.

18. A compound according to claim 13 , wherein

R 4 and R 5 independently stand for C 1 -C 6 -alkyl

or

R 4 and R 5 together form a ring of the group

 V, W and Y stand for —CH 2 —, and

n stands for 2.

19. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound according to claim 1 .

20. A process for preparing a compound of Formula (I) according to claim 1 , comprising

coupling a compound of formula (II)

 with a compound of formula (III)

 under acidic conditions,

wherein Q, X, R1, R2, R3, R4, and R5 have the meanings indicated for formula I.

21. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound according to claim 2 .

22. A pharmaceutical composition according to claim 19 , which is suitable for enteral, parenteral or oral administration.

23. A pharmaceutical composition according to claim 21 , which is suitable for enteral, parenteral and oral administration.

24. A method for treating hormone-independent human breast cancer comprising administering to a patient in need thereof an effective amount of a pharmaceutical composition according to claim 19 .

25. A method for treating human non-small-cell lung cancer comprising administering to a patient in need thereof an effective amount of a pharmaceutical composition according to claim 19 .

26. A method for treating hormone-independent human prostate cancer comprising administering to a patient in need thereof an effective amount of a pharmaceutical composition according to claim 19 .

27. A method for treating hormone-independent, multiple pharmaceutical agent-resistant human breast cancer comprising administering to a patient in need thereof an effective amount of a pharmaceutical composition according to claim 19 .