6-oxazol-4-ylmetholmethoxy-alko-alkoxymethyl substituted benzoic acid derivatives forming peroxisome proliferator—activated receptor (PPAR) ligands, process for their preparation and methods of use thereof

1. A compound of formula I

wherein:

R1 is selected from the group consisting of H, (C1-C6)-alkyl, O—(C1-C2)-alkyl, (C1-C6)-alkylmercapto, trifluoromethoxy, trifluoromethylmercapto, F, CF3, phenyl and phenoxy;

R2 is selected from the group consisting of H, O—(C1-C3)-alkyl, (C1-C3)-alkyl, CF 3 and trifluoromethoxy; or

R1 and R2 are fused together with the phenyl ring to form a naphthyl;

R3 is selected from the group consisting of (C1-C6)-alkyl, phenyl, and cyclohexyl;

R4 and R5 independently are H or CH 3 , provided that when one of R4 and R5 is CH3, m then must be 1;

R6 is selected from the group consisting of H and (C1-C6)-alkyl;

X is CH, if n=1, or S if n=0;

n is 0 or 1; and

m is 1 or 2;

or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein one of R1 and R2 is not H; or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 1 , wherein:

R1 is H;

R2 is selected from the group consisting of O—(C1-C3)-alkyl, (C1-C3)-alkyl, CF 3 and trifluoromethoxy;

R3 is (C1-C6)-alkyl;

R4, R5 and R6 are H;

X is CH;

n is 1; and

m is 1;

or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 1 , wherein:

R1 is selected from the group consisting of (C1-C6)-alkyl, O—(C1-C2)-alkyl, trifluoromethoxy, trifluoromethylmercapto, F, phenyl and phenoxy;

R2 is H;

R4, R5 and R6 are H;

X is CH;

n is 1; and

m is 1;

or a pharmaceutically acceptable salt thereof.

5. The compound according to claim 1 , wherein:

R1 and R2 independently are H, Me, O—CH 3 , or

R1 and R2 are fused together with the phenyl ring to form naphthyl;

R3 is (C1-C6)-alkyl;

R4, R5 and R6 are H;

X is CH;

n is 1; and

m is 1;

or a pharmaceutically acceptable salt thereof.

6. The compound according to claim 1 , wherein:

R1 is selected from the group consisting of H, F and CH 3 ;

R2 is selected from the group consisting of H, O—CH 3 and CF 3 ;

R3 is (C1-C6)-alkyl;

R4 and R5 are CH 3 ;

R6 is H;

X is CH;

n is 1; and

m is 1;

or a pharmaceutically acceptable salt thereof.

7. The compound according to claim 1 ,

wherein:

R1 is selected from the group consisting of H, F, CH 3 and phenyl

R2 is selected from the group consisting of H, O—CH, CH 3 and CF 3 ;

R3 is (C1-C6)-alkyl;

R4, R5 and R6 are H;

X is CH;

n is 1; and

m is 2;

or a pharmaceutically acceptable salt thereof.

8. A pharmaceutical composition comprising at least one compound according to claim 1 or a pharmaceutically acceptable salt thereof in combination with a pharmaceutically acceptable carrier.

9. The pharmaceutical composition according to claim 8 , further comprising at least one-secondary pharmaceutically active compound wherein the secondary pharmaceutically active compound is effective in the therapeutic treatment of metabolic disturbance or a disorders associated therewith.

10. The pharmaceutical composition according to claim 9 wherein the secondary pharmaceutically active compound is an anti diabetic compound.

11. The pharmaceutical composition according to claim 9 wherein the secondary pharmaceutically active compound is a lipid modulator.

12. A method for treating a disorder of fatty acid metabolism or glucose utilization disorder, in a patient in need thereof, comprising administering to the patient a pharmaceutically effective amount of the compound according to claim 1 or a pharmaceutically acceptable salt thereof.

13. A method for treating a disorder in which insulin resistance is involved, in a patient in need thereof; comprising administering to the patient a pharmaceutically effective amount of the compound according to claim 1 or a pharmaceutically acceptable salt thereof.

14. A method for treating a disorders of diabetes mellitus or a physiological manifestation associated therewith, in a patient in need thereof; comprising administering to the patient a pharmaceutically effective amount of the compound according to claim 1 or a pharmaceutically acceptable salt thereof.

15. A method for treating dyslipidemia or a physiological manifestation associated therewith, in a patient in need thereof, comprising administering to the patient a pharmaceutically effective amount of the compound according to claim 1 or a pharmaceutically acceptable salt thereof.

16. A method for treating a condition associated with the metabolic syndrome or a physiological manifestation associated therewith, in a patient in need thereof, comprising administering to the patient a pharmaceutically effective amount of the compound according to claim 1 or a pharmaceutically acceptable salt thereof.

17. A method for treating a disorder of fatty acid metabolism or glucose utilization disorder or a physiological manifestation associated therewith, in a patient in need thereof, comprising administering to the patient a pharmaceutically effective amount of the compound according to claim 1 or a pharmaceutically acceptable salt thereof.

18. A method for treating a disorder in which insulin resistance is involved or a the physiological manifestation associated therewith, in a patient in need thereof, comprising administering to the patient a pharmaceutically effective amount of the compound according to claim 1 or a pharmaceutically acceptable salt thereof.

19. A process for producing a pharmaceutical composition comprising at least one compound according to claim 1 or a pharmaceutically acceptable salt thereof which comprises mixing the compound according to claim 1 or the pharmaceutically acceptable salt thereof with a pharmaceutically suitable carrier, and bringing this mixture into a form suitable for administration.

20. A compound, which is 2-{3-[2-(4-Fluorophenyl)oxazol-4-ylmethoxy]-2,2-dimethylpropoxymethyl}-6-methylbenzoic acid, or a pharmaceutically acceptable salt thereof.

21. A pharmaceutical composition comprising the compound according to claim 20 or a pharmaceutically acceptable salt thereof in combination with a pharmaceutically acceptable carrier.