Quinoline and isoquinoline derivatives, a process for their production and their use as inflammation inhibitors

1. A compound of formula I

wherein

A stands for an aryl group, a benzyl group or a phenethyl group, optionally substituted by;

one or more radicals of C 1 -C 5 -alkyl, C 1 -C 5 -alkoxy, C 1 -C 5 -alkylthio, C 1 -C 5 -perfluoroalkyl, halogen, hydroxy, cyano, or nitro; or

—O—(CH 2 ) n —O—, —O—(CH 2 ) n —CH 2 —, —O—CH═CH—, or —(CH 2 ) n+2 —, wherein n=1 or 2, and wherein the two terminal atoms in these groups are linked with directly adjacent ring-carbon atoms of the aryl, benzyl or phenethyl group to form a fused ring;

or

NR 4 R 5 , wherein R 4 and R 5 , independently of one another, are hydrogen, C 1 -C 5 -alkyl or (CO)—C 1 -C 5 -alkyl,

R 1 and R 2 , independently of one another, are a hydrogen atom, a methyl or an ethyl group or together with the carbon atom of the chain from a C 3 -C 6 -cycloalkyl ring,

R 3 means a C 1 -C 3 -alkyl group or a C 1 -C 3 -alkyl group optionally partially or completely fluorinated,

B means a methylene group that is optionally substituted by a methyl, an ethyl, or a carbonyl group, and

Q means a quinolinyl group or an isoquinolinyl group that is linked via any position and that optionally can be substituted by one or more radicals from the group C 1 -C 5 -alkyl, wherein C 1 -C 5 -alkyl is optionally substituted by 1-3 hydroxy groups and/or 1-3 COOR 6 groups; C 1 -C 5 -alkoxy; C 1 -C 5 alkylthio; C 1 -C 5 -perfluoroalkyl; halogen; hydroxy; a carbonyl-oxygen atom; cyano; nitro; or NR 4 R 5 ,

wherein R 4 and R 5 , independently of one another, are hydrogen, C 1 -C 5 -alkyl or (CO)—C 1 -C 5 -alkyl;

COOR 6 , wherein R 6 means hydrogen or a C 1 -C 5 -alkyl group;

(CO)NR 7 R 8 , wherein R 7 and R 8 , independently of one another, mean hydrogen or a C 1 -C 5 -alkyl group;

or a (C 1 -C 5 -alkylen)-O—(CO)—(C 1 -C 5 )alkyl group; wherein, the C 1 -C 5 -alkyl groups in A, and R 4 -R 8 are optionally substituted by 1-3 hydroxy groups and/or 1-3 COOR 6 groups;

or a racemate, a separately present stereoisomer, or a physiologically compatible salt thereof.

2. Compounds according to claim 1 , wherein Q means a quinolinyl group or an isoquinolinyl group that is linked via any position and that optionally can be substituted by one or more radicals from the group C 1 -C 5 -alkyl, a carbonyl-oxygen atom, COOR 6 , wherein R 6 means hydrogen or a C 1 -C 5 -alkyl group, (CO)NR 7 R 8 , wherein R 7 and R 8 , independently of one another, mean hydrogen or a C 1 -C 5 -alkyl group, or a (C 1 -C 5 -alkylene)-O—(CO)—(C 1 -C 5 )alkyl group, wherein the C 1 -C 5 -alkyl optionally can be substituted by 1-3 hydroxy groups or 1-3 COOR 6 groups.

3. A compound of formula I

wherein

A stands for an aryl group, a benzyl group or a phenethyl group, optionally substituted by;

one or more radicals of C 1 -C 5 -alkyl, C 1 -C 5 -alkoxy, C 1 -C 5 -alkylthio, C 1 -C 5 -perfluoroalkyl, halogen, hydroxy, cyano, or nitro; or

—O—(CH 2 ) n —O—, —O—(CH 2 ) n —CH 2 —, —O—CH═CH—, or —(CH 2 ) n+2 —, wherein n=1 or 2, and wherein the two terminal atoms in these groups are linked with directly adjacent ring-carbon atoms of the aryl, benzyl or phenethyl group to form a fused ring;

or

NR 4 R 5 ,

wherein R 4 and R 5 , independently of one another, are hydrogen, C 1 -C 5 -alkyl or (CO)—C 1 -C 5 -alkyl,

R 1 and R 2 , independently of one another, mean a hydrogen atom, a methyl or an ethyl group or together with the carbon atom of the chain form a C 3 -C 6 -cycloalkyl ring,

R 3 means a C 1 -C 3 -alkyl group or a C 1 -C 3 -alkyl group optionally partially or completely fluorinated,

B means a methylene group that is optionally substituted by a methyl, an ethyl, or a carbonyl group, and

Q means a quinolinyl group or an isoquinolinyl group that is linked via any position and that optionally can be substituted by one or more radicals from the group C 1 -C 5 -alkyl, 1 -C 5 -alkoxy, C 1 -C 5 -perfluoroalkyl, halogen, hydroxy, cyano, nitro or NR 4 R 5 ,

wherein R 4 and R 5 , independently of one another, can be hydrogen, C 1 -C 5 -alkyl or (CO)—C 1 -C 5 -alkyl,

or a racemate, a separately present stereoisomer or a physiologically compatible salt.

4. A compounds according to claim 2 , wherein B means a methylene group.

5. A compounds according to claim 2 , wherein A is an aryl radical.

6. A compounds according to claim 5 , wherein A is an aryl radical optionally substituted by one or more radicals from the group C 1 -C 5 -alkyl, C 1 -C 5 -alkoxy, C 1 -C 5 -perfluoroalkyl, halogen, hydroxy, or nitro, or

—O—(CH 2 ) n —O—, —O—(CH 2 ) n —CH 2 —, —O—CH═CH—, or —(CH 2 ) n+2 —, wherein n=1 or 2, and their terminal atoms in these groups are linked with immediately adjacent ring-carbon atoms.

7. A compound according to claim 2 , wherein R 1 and R 2 together with the carbon atom of the chain mean a C 3 -C 6 -cycloalkyl ring.

8. A compounds according to claim 2 , wherein Q means an optionally substituted quinolinyl group that is linked via any position.

9. A compound according to claim 5 , wherein A is a phenyl radical that is substituted by a hydroxy group, or a methoxy group, or a halogen atom.

10. A compounds according to claim 1 , wherein the compound is (+)-enantiomer.

11. A compound according to claim 1 , wherein the compound is (−)-enantiomer.

12. A pharmaceutical composition comprising a compound according to claim 1 , and a pharmaceutically acceptable vehicle.

13. A method of treating an inflammatory disease, comprising administrating an effective amount of a compound according to claim 1 to a patient in need thereof.

14. A compound according to claim 5 , wherein A is phenyl or naphthyl.

15. A compound according to claim 1 , wherein the C 1 -C 5 alkyl groups in A, R 4 , R 5 , R 6 , R 7 , and R 8 are, independently, a methyl, an ethyl, an n-propyl, an iso-propyl, an n-butyl, an iso-butyl, a tert-butyl, an n-pentyl, a 2,2-dimethylpropyl, a 2-methylbutyl, or a 3-methylbutyl group, optionally substituted by hydroxy.

16. A compound according to claim 1 , wherein R 1 and R 2 are together a cyclopropyl ring.

17. A compound according to claim 1 , wherein B is a methylene group.

18. A compound according to claim 1 , wherein the C 1 -C 5 alkoxy group in A and Q is a methoxy or an ethoxy group.

19. A compound according to claim 1 , wherein the C 1 -C 5 -alkylthio group in A and Q is a methylthio or an ethylthio group.

20. A compound according to claim 1 , wherein Q is a quinoline ring linked at the 4-, 5- or 8-position or an isoquinoline ring linked at the 1-position.