CCR2 antagonists and uses thereof

1. A compound according to formula (I),

wherein

R 1 is -L 1 -R 6 ,

wherein L 1 is a linker selected from a bond or a group selected from among —C 1 -C 2 -alkylene,

wherein R 6 is a ring selected from among —C 3 -C 8 -cycloalkyl, —C 3 -C 8 -heterocyclyl, -C 5 -C 10 -aryl, and -C 5 -C 10 -heteroaryl,

wherein the ring R 6 is optionally substituted with one or more groups selected from among —CF 3 , —O—CF 3 , —CN, —C 1 -C 6 -alkyl, and -halogen,

or wherein the ring R 6 is optionally substituted with one or more groups selected from among —C 1 -C 6 -alkyl, —O—C 1 -C 6 -alkyl, -C 5 -C 10 -aryl, -C 5 -C 10 -heteroaryl, —C 3 -C 8 -cycloalkyl, —C 3 -C 8 -heterocyclyl, —C 2 -C 6 -alkenyl, and —C 2 -C 6 -alkynyl, optionally being substituted by one or more groups selected from among —OH, —NH 2 , —C 1 -C 6 -alkyl, —O—C 1 -C 6 -alkyl, —CN, —CF 3 , —OCF 3 , halogen, and ═O;

wherein R 2 is selected from among —H, —OCH 3 , —C 1 -C 3 -alkyl, and -cyclopropyl;

wherein R 3 is selected from among —H, -methyl, -ethyl, -propyl, -i-propyl, -cyclopropyl, —OCH 3 , —CF 3 , and —CN;

wherein R 4 is selected from among —H, and —C 1 -C 3 -alkyl;

wherein R 5 is selected from among —H, —C 1 -C 4 -alkyl, —OH, —O—C 1 -C 4 -alkyl, -halogen, —CN, —CF 3 , and —OCF 3 ;

wherein G and E are independently selected from among C or N;

wherein n is 1, 2 or 3;

as well as in form of their acid addition salts with pharmacologically acceptable acids.

2. The compound of formula (I) according to claim 1 ,

wherein R 1 is -L 1 -R 6 ,

and wherein L 1 is a bond or wherein L 1 denotes methylene,

and wherein R 6 is a ring selected from among -cyclopropyl, -cyclobutyl, -cyclopentyl, -cyclohexyl, -cycloheptyl, -pyrrolidinyl, -piperidinyl, -azepanyl, -tetrahydrofuranyl, -tetrahydropyranyl, -oxepanyl, -phenyl, -pyridyl, and -furanyl,

wherein the ring R 6 is optionally substituted with one or more groups selected from among —F, —Cl, -methyl, -ethyl, -propyl, -i-propyl, -cyclopropyl, -t-butyl, —CF 3 , —O—CF 3 , —CN, —O-methyl, -furanyl and -phenyl, wherein said -phenyl is optionally independently substituted by one or more groups selected from among —C 1 -C 3 -alkyl, halogen, —OCH 3 , —CF 3 , and —OCF 3 .

3. The compound of formula (I) according to claim 1 ,

wherein R 1 is -L 1 -R 6 ,

and wherein L 1 is a bond or wherein L 1 denotes methylene,

and wherein R 6 is a ring selected from among —C 3 -C 8 -heterocyclyl, and -C 5 -C 10 -aryl,

wherein the ring R 6 is optionally substituted with one or more groups selected from among —CF 3 , —O—CF 3 , —CN, —C 1 -C 6 -alkyl, and -halogen,

or wherein the ring R 6 is optionally substituted with one or more groups selected from among —C 1 -C 6 -alkyl, -C 5 -C 10 -aryl, -C 5 -C 10 -heteroaryl optionally being substituted by one or more groups selected from —CF 3 , and —OCF 3 .

4. The compound of formula (I) according to claim 1 , wherein R 1 denotes a group selected from among formula (II)

wherein R 7 is a ring selected from among-C 5 -C 10 -aryl, and -C 5 -C 10 -heteroaryl,

wherein the ring R 7 is optionally substituted with one or more groups selected from among —CF 3 , —O—CF 3 , —CN, —C 1 -C 6 -alkyl, and -halogen.

5. The compound of formula (I) according to claim 1 , wherein R 1 denotes a group selected from among formula (III) and (IV)

wherein R 8 is selected from among

—CF 3 , —O—CF 3 , —CN, —C 1 -C 6 -alkyl, and -halogen.

6. The compound of formula (I) according to claim 1 , wherein R 2 denotes —CH 3 .

7. The compound of formula (I) according to claim 1 , wherein R 3 is selected from among H, and methyl.

8. The compound of formula (I) according to claim 1 , wherein R 4 denotes —H.

9. The compound of formula (I) according to claim 1 , wherein R 5 denotes —H.

10. The compound of formula (I) according to claim 1 , wherein G and E are N.

11. The compound of formula (I) according to claim 1 , wherein n is 2.

12. A method for the treatment of inflammatory diseases comprising administering to a patient in need thereof a therapeutic amount of compound according to claim 1 .

13. The method according to claim 12 , wherein the inflammatory diseases are selected from inflammatory diseases of the respiratory tract.

14. The method according to claim 13 , wherein the diseases are selected from chronic obstructive pulmonary disease, asthma, and cystic fibrosis.

15. A method for the treatment of neurologic diseases comprising administering to a patient in need thereof a therapeutic amount of compound according to claim 1 .

16. A method for the treatment of diabetes mellitus comprising administering to a patient in need thereof a therapeutic amount of compound according to claim 1 .

17. A method for the treatment of peripheral atherosclerotic disease comprising administering to a patient in need thereof a therapeutic amount of compound according to claim 1 .

18. A method for the treatment of diabetic nephropathy comprising administering to a patient in need thereof a therapeutic amount of compound according to claim 1 .

19. The method of claim 15 , wherein the neurologic disease is selected from pain diseases.

20. The method of claim 19 , wherein the pain diseases are selected from inflammatory and neuropathic pain disease.

21. The compound according to claim 1 selected from the group consisting of

and the acid addition salts with pharmacologically acceptable acids thereof.