CCR2 antagonists

1. A compound according to formula (Ia),

wherein A′ is —NH-L 1 -R 7 ,

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

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

or wherein the ring R 7 is optionally substituted with one or more groups selected from among -C 5 -C 10 -aryl, -C 5 -C 10 -heteroaryl, —C 3 -C 8 -cycloalkyl, —C 3 -C 8 -heterocyclyl, optionally being substituted by one or more groups selected from among —OH, —NH 2 , —C 1 -C 4 -alkyl, —O—C 1 -C 6 -alkyl, —CN, —CF 3 , —OCF 3 , halogen, and ═O,

or wherein the ring R 7 is optionally further bi-valently substituted on two neighbouring ring atoms, such that an annellated ring is formed by one or more groups selected from among —C 1 -C 6 -alkylene, —C 2 -C 6 -alkenylene and —C 4 -C 6 -alkynylene, in which one or two carbon centers may optionally be replaced by 1 or 2 hetero atoms selected from N, O and S, the bivalent group being optionally substituted by one or more groups selected from —OH, —NH 2 , —C 1 -C 4 -alkyl, —O—C 1 -C 6 -alkyl, —CN, —CF 3 , —OCF 3 , halogen, and ═O,

wherein R 1 is —H;

wherein R 2 is selected from among —H, -halogen, —CN, —O—C 1 -C 4 -alkyl, —C 1 -C 4 -alkyl, —CH═CH 2 , —C≡CH, -cyclopropyl, —CF 3 , —OCF 3 , —OCF 2 H, and —OCFH 2 ;

wherein R 3 is —H;

wherein R 6 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 Z is C;

wherein n is 2;

wherein R 4 and R 5 are independently selected from among an electron pair, —H, and a group selected from among —C 1 -C 6 -alkyl, —NH 2 , —C 3 -C 8 -cycloalkyl, —C 3 -C 8 -heterocyclyl, —C 5 -C 10 -aryl, -C 5 -C 10 -heteroaryl, and —C(O)—N(R 8 ,R 8′ ), with R 8 and R 8′ independently being selected from among —H, and —C 1 -C 6 -alkyl, and wherein R 4 and R 5 if different from an electron pair or —H are optionally independently substituted with one or more groups selected from among -halogen, —OH, —CF 3 , —CN, —C 1 -C 6 -alkyl, —O—C 1 -C 6 -alkyl, —O—C 3 -C 8 -cycloalkyl, —O—C 3 -C 8 -heterocyclyl, —O—C 5 -C 10 -aryl, —O—C 5 -C 10 -heteroaryl, —C 0 -C 6 -alkylene-CN, —C 0 -C 4 -alkylene-O—C 1 -C 4 -alkyl, —C 0 -C 4 -alkylene-O—C 3 -C 8 -cycloalkyl, —C 0 -C 4 -alkylene-O—C 3 -C 8 -heterocyclyl, —C 0 -C 4 -alkylene-O-C 5 -C 10 -aryl, —C 0 -C 4 -alkylene-O-C 5 -C 10 -heteroaryl, —C 0 -C 4 -alkylene-Q-C 0 -C 4 -alkyl-N(R 9 ,R 9′ ), —C 0 -C 4 -alkylene-N(R 10 )-Q-C 1 -C 4 -alkyl, —C 0 -C 4 -alkylene-N(R 10 )-Q-C 3 -C 8 -cycloalkyl, —C 0 -C 4 -alkylene-N(R 10 )-Q-C 3 -C 8 -heterocyclyl, —C 0 -C 4 -alkylene-N(R 10 )-Q-C 5 -C 10 -aryl, —C 0 -C 4 -alkylene-N(R 10 )-Q-C 5 -C 10 -heteroaryl, —C 0 -C 4 -alkylene-Q-N(R 11 ,R 11′ ), —C 0 -C 4 -alkylene-N(R 12 )-Q-N(R 13 ,R 13′ ), —C 0 -C 4 -alkylene-R 14 , —C 0 -C 4 -alkylene-Q-C 1 -C 6 -alkyl, —C 0 -C 4 -alkylene-Q-C 3 -C 8 -cycloalkyl, —C 0 -C 4 -alkylene-Q-C 3 -C 8 -heterocyclyl, —C 0 -C 4 -alkylene-Q-C 5 -C 10 -aryl, —C 0 -C 4 -alkylene-Q-C 5 -C 10 -heteroaryl, —C 0 -C 4 -alkylene-O-Q-N(R 15 ,R 15′ ), and —C 0 -C 4 -alkylene-N(R 16 )-Q-O—(R 17 ),

wherein Q is selected from among —C(O)—, and —SO 2 —,

wherein R 12 , R 16 , are independently selected from among —H, —C 1 -C 6 -alkyl, and —C 3 -C 6 -cycloalkyl,

wherein R 9 , R 9′ , R 10 , R 11 , R 11′ , R 13 , R 13′ , R 15 , R 15′ , are independently selected from among —H, —C 1 -C 6 -alkyl, and —C 3 -C 6 -cycloalkyl,

or wherein R 9 and R 9′ , R 11 and R 11′ , R 13 and R 13′ , R 15 and R 15′ together form a —C 2 -C 6 -alkylene group,

wherein R 14 and R 17 are independently selected from among —H, —C 1 -C 6 -alkyl, —C 5 -C 10 -aryl, —C 5 -C 10 -heteroaryl, —C 3 -C 8 -cycloalkyl, and —C 3 -C 8 -heterocyclyl, wherein said —C 3 -C 8 -heterocyclyl optionally comprises nitrogen and/or —SO 2 — in the ring,

and wherein R 14 and R 17 are optionally substituted with one or more groups selected from among —OH, —OCH 3 , —CF 3 , —OCF 3 , —CN, -halogen, —C 1 -C 4 -alkyl, ═O, and —SO 2 —C 1 -C 4 -alkyl,

or wherein R 4 and/or R 5 are independently selected from among an electron pair, —H, and a group of the structure -L 2 -R 18 ,

wherein L 2 is selected from among —NH— and —N(C 1 -C 4 -alkyl)-,

wherein R 18 is selected from among —C 5 -C 10 -aryl, —C 5 -C 10 -heteroaryl, —C 3 -C 8 -cycloalkyl, and —C 3 -C 8 -heterocyclyl,

wherein R 18 is optionally substituted by one or more groups selected from among halogen, —CF 3 , —OCF 3 , —CN, —OH, —O—C 1 -C 4 -alkyl, —C 1 -C 6 -alkyl, —NH—C(O)—C 1 -C 6 -alkyl, —N(C 1 -C 4 -alkyl)-C(O)—C 1 -C 6 -alkyl, —C(O)—C 1 -C 6 -alkyl, —S(O) 2 —C 1 -C 6 -alkyl, —NH—S(O) 2 —C 1 -C 6 -alkyl, —N(C 1 -C 4 -alkyl)-S(O) 2 —C 1 -C 6 -alkyl, and —C(O)—O—C 1 -C 6 -alkyl,

and wherein R 4 , R 5 and R 18 are optionally further substituted by spiro-C 3 -C 8 -cycloalkyl or spiro-C 3 -C 8 -heterocyclyl such that together with R 4 , R 5 and/or R 18 a spirocycle is formed, wherein said spiro-C 3 -C 8 -heterocyclyl optionally comprises one or more groups selected from among nitrogen, —C(O)—, —SO 2 —, and —N(SO 2 —C 1 -C 4 -alkyl)- in the ring,

or wherein R 4 , R 5 and R 18 are optionally further bi-valently substituted by one or more spirocyclic or annellated ring forming groups selected from among —C 1 -C 6 -alkylene, —C 2 -C 6 -alkenylene, and —C 4 -C 6 -alkynylene, in which one or two carbon centers may optionally be replaced by one or two hetero atoms selected from among N, O and S and which may optionally be substituted by one or more groups on one ring atom or on two neighbouring ring atoms selected from among —OH, —NH 2 , —C 1 -C 3 -alkyl, O—C 1 -C 6 -alkyl, —CN, —CF 3 , —OCF 3 , and halogen;

or a pharmacologically acceptable salt thereof.

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

R 7 is a ring selected from among-C 3 -C 8 -cycloalkyl, and —C 3 -C 8 -heterocyclyl, —C 5 -C 10 -aryl,

wherein the ring R 7 is optionally substituted with one or more groups selected from —C 1 -C 6 -alkyl,

or wherein the ring R 7 is optionally substituted with one or more groups selected from −C 5 -C 10 -aryl, optionally being substituted by one or more groups selected from among —C 1 -C 4 -alkyl, —CF 3 , —OCF 3 , and halogen.

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

wherein R 7 denotes a group selected from among formula (II)

wherein R 19 denotes the ring —C 5 -C 10 -aryl,

wherein the ring R 19 is optionally substituted with one or more groups selected from —C 1 -C 4 -alkyl.

4. The compound of formula (Ia) according to claim 1 ,

wherein R 7 is a ring selected from among —C 3 -C 8 -cycloalkyl, and -C 5 -C 10 -aryl,

wherein the ring R 7 is optionally substituted with one or more groups selected from —C 1 -C 6 -alkyl,

or wherein the ring R 7 is optionally substituted with one or more groups selected from -phenyl, optionally being substituted by one or more groups selected from among —C 1 -C 4 -alkyl.

5. The compound of formula (Ia) according to claim 1 ,

wherein R 2 is selected from among —H, —O—C 1 -C 4 -alkyl, and —C 1 -C 4 -alkyl.

6. The compound of formula (Ia) according to claim 1 ,

wherein R 6 denotes —H.

7. The compound of formula (Ia) according to claim 1 ,

wherein R 4 denotes —H, and wherein R 5 denotes a group of the structure -L 2 -R 18 ,

wherein L 2 is a group selected from among —NH—, and —N(CH 3 )—,

wherein R 18 is —C 6 -heterocyclyl comprising 1 hetero atom selected from 0,

wherein R 18 is optionally substituted by —O—CH 3 ;

or wherein R 4 denotes —H and R 5 is a heterocyclyl selected from pyrrolidine and piperidine wherein said heterocyclyl is optionally substituted with one or more groups selected from —N(C 0 -C 1 -alkyl)-SO 2 —CH 3 .

8. 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 .

9. The method according to claim 8 , wherein the inflammatory diseases are selected from inflammatory diseases of the respiratory tract.

10. The method according to claim 9 , wherein the diseases are selected from chronic obstructive pulmonary disease, asthma, and cystic fibrosis.

11. 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 .

12. 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 .

13. 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 .

14. A method for the treatment of inflammatory and neuropathic pain disease comprising administering to a patient in need thereof a therapeutic amount of compound according to claim 1 .

15. The compound of formula (Ia) according to claim 1 , wherein the compound is selected from the group consisting of

or a pharmacologically acceptable salt thereof.