Cycloalkyl-substituted amino acid derivatives, processes for their preparation and their use as pharmaceuticals

1. A compound having the formula I

in which:

Ring A is (C 3 -C 8 )-cycloalkanediyl or (C 3 -C 8 )-cycloalkenediyl;

R1, R2 independently of one another are H, F, Cl, Br, CF 3 , OCF 3 , (C 1 -C 6 )-alkyl, O—(C 1 -C 6 )-alkyl, SCF 3 , SF 5 , OCF 2 —CHF 2 , (C 6 -C 10 )-aryl, (C 6 -C 10 )-aryloxy, OH, NO 2 ; or

R1 and R2 together with the phenyl ring form fused, partially or unsaturated bicyclic (C 6 -C 10 )-aryl;

R3 is H, (C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkyl, (C 1 -C 3 )-alkyl-(C 3 -C 8 )-cycloalkyl, phenyl, (C 1 -C 3 )-alkyl-phenyl, or (C1-C3)-alkyl which is fully or partially substituted by F;

W is CH;

o is 1;

X is (C 1 -C 6 )-alkanediyl, where in the alkanediyl group one or more carbon atoms may be replaced by oxygen atoms;

n is 0-2;

R4 is H or (C 1 -C 6 )-alkyl;

R5 is H or (C 1 -C 6 )-alkyl;

R6 is H, (C 1 -C 6 )-alkyl or F;

R7 is H; F; (C 1 -C 6 )-alkoxy; (C 2 -C 6 )-alkenyl; (C 2 -C 6 )-alkynyl; (C 3 -C 8 )-cycloalkyl; phenyl which may be unsubstituted or substituted by one or more radicals from the group consisting of hydroxy, (C 1 -C 6 )-alkoxy, F and CF 3 ; (C 1 -C 6 )-alkyl which may be unsubstituted or substituted by one or more radicals selected from the group consisting of hydroxyl, phenyl, (C 1 -C 6 )-alkoxy and NR11R12;

with the proviso that R7 is not NR11 R12 or (C 1 -C 6 )-alkoxy if R6=F;

R7 and R9 together with the atoms that carry them are pyrrolidine if n=0;

R6 and R7 together with the carbon atom that carries them are (C 3 -C 8 )-cycloalkyl;

R8 is H, (C 1 -C 6 )-alkyl;

R9 is H, (C 1 -C 6 )-alkyl, (C 2 -C 6 )-alkenyl, (C 2 -C 6 )-alkynyl, (C 1 -C 4 )-alkyl-(C 6 -C 10 )-aryl, (C 1 -C 4 )-alkyl-O—(C 1 -C 4 )-alkyl, phenyl-(C 1 -C 4 )-alkyl;

R10 is H, (C 1 -C 6 )-alkyl-phenyl, (C 1 -C 6 )-alkyl;

R11 is H, (C 1 -C 6 )-alkyl-phenyl, (C 1 -C 6 )-alkyl;

R12 is H, (C 1 -C 6 )-alkyl-phenyl, (C 1 -C 6 )-alkyl;

a physiologically acceptable salt of the compound;

a solvate of the compound; or

a physiologically effective derivative of the compound.

2. The compound of claim 1 , in which

Ring A is (C 3 -C 8 )-cycloalkanediyl or (C 3 -C 8 )-cycloalkenediyl;

X is (C 1 -C 6 )-alkanediyl, wherein the C1 or C2 carbon atom (to Ring A) of the alkanediyl group may be replaced by an oxygen atom.

3. The compound of claim 1 , in which

Ring A is cis-cyclohexane-1,3-diyl

R1 is Br, CF 3 , OCF 3 , (C 1 -C 6 )-alkyl, O—(C 1 -C 6 )-alkyl;

R2 is H, (C1-C6)-alkyl, O—(C1-C6)-alkyl or

R1 and R2 together with the phenyl ring form naphthyl;

R3 is CF 3 , (C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkyl, phenyl;

W is CH;

o is 1;

X is CH 2 O or CH 2 —O—CH 2 ;

n is 0;

R6 is H or (C 1 -C 6 )-alkyl;

R7 is (C 1 -C 6 )-alkyl, where alkyl may be unsubstituted or substituted by phenyl;

R7 and R9 together with the atoms that carry them are pyrrolidine if n=0;

R6 and R7 together with the carbon atom that carries them are (C 3 -C 6 )-cycloalkyl;

R8 is H; and

R9 is H, (C 1 -C 6 )-alkyl or benzyl.

4. A pharmaceutical composition, comprising the compound of claim 1 and a pharmaceutically acceptable carrier.

5. The pharmaceutical composition of claim 4 , further comprising an active compound having a favorable effect on a metabolic disorder or disease.

6. The pharmaceutical composition of claim 4 , further comprising an antidiabetic.

7. The pharmaceutical composition of claim 4 , further comprising a lipid modulator.

8. A method for treating a disorder in which insulin resistance is involved in a patient, comprising administering a therapeutically effective amount of the compound of claim 1 to the patient.

9. A method for treating diabetes mellitus and its sequelae in a patient, comprising administering a therapeutically effective amount of the compound of claim 1 to the patient.

10. The method of claim 8 , further comprising administering a at least one further active compound for treating a disorder in which insulin is involved.

11. A process for preparing a pharmaceutical comprising the compound of claim 1 , comprising the steps of:

(a) mixing the compound with a pharmaceutically acceptable carrier, and;

(b) bringing the mixture into a form suitable for administration.

12. A pharmaceutical composition comprising the compound of claim 2 and a pharmaceutically acceptable carrier.

13. A method for treating a disorder in which insulin resistance is involved in a patient, comprising administering a therapeutically effective amount of the compound of claim 2 to the patient.

14. A method for treating diabetes mellitus and its sequelae in a patient, comprising administering a therapeutically effective amount of the compound of claim 2 to the patient.

15. A pharmaceutical composition comprising the compound of claim 3 and a pharmaceutically acceptable carrier.

16. A method for treating a disorder in which insulin resistance is involved in a patient, comprising administering a therapeutically effective amount of the compound of claim 3 to the patient.

17. A method for treating diabetes mellitus and its sequelae in a patient, comprising administering a therapeutically effective amount of the compound of claim 3 to the patient.