Competitive PPAR-gamma antagonists

1. A compound of the formula (I), or a stereoisomer, or salt thereof:

wherein

R 1 is selected from a non-substituted, monosubstituted or polysubstituted aryl or heteroaryl residue,

R 2 is a radical of the formula (III),

wherein

X and Z are independently selected from C or N,

R 9 to R 12 are independently selected from H, hydroxyl, a non-substituted, monosubstituted or polysubstituted C 1 -C 18 -alkyl, wherein the alkyl can be straight, branched or cyclic, alkenyl, trifluormethyl, a non-substituted, monosubstituted or polysubstituted aryl or heteroaryl residue, a non-substituted, monosubstituted or polysubstituted benzyl group, an acyl group, or a branched or heteroatom- or aryl-substituted acyl group, an alkoxy substituent, the alkyl group thereof is branched, non-branched or cyclic, an alkyl group bound through a sulfur atom, or a sulfonyl group, or a nitrogen substituent, or fluoro, chloro, bromo, iodo, —CN or a hetero substituent, if X is N then R 11 is absent, and if Z is N then R 12 is absent; and

R 1 and R 2 are different, and

R 3 is a non-substituted, monosubstituted or polysubstituted C 1 -C 10 -alkyl, wherein the alkyl can be straight, branched or cyclic.

2. The compound according to claim 1 , wherein R 3 is non-substituted C 1 -C 8 alkyl.

3. The compound according to claim 1 , wherein R 1 is a radical with the formula (II),

wherein R 4 to R 8 are independently selected from H, OH, SH, a non-substituted, monosubstituted or polysubstituted C 1 -C 18 -alkyl, wherein the alkyl can be straight, branched or cyclic, alkenyl, trifluormethyl, a non-substituted, monosubstituted or polysubstituted aryl or heteroaryl residue, a non-substituted, monosubstituted or polysubstituted benzyl group, an acyl group, or a branched or heteroatom- or aryl-substituted acyl group, an alkoxy substituent, the alkyl group thereof is branched, non-branched or cyclic, an alkyl group bound through a sulfur atom, or a sulfonyl group, or a nitrogen substituent, or fluoro, chloro, bromo, iodo, —CN or a hetero substituent.

4. The compound according to claim 3 , wherein R 4 , R 5 , R 7 and R 8 are H, and R 6 is trifluormethyl (—CF 3 ).

5. The compound according to claim 1 , wherein Z is N, and X is C.

6. The compound according to claim 5 , wherein R 10 is H, R 12 is absent, R 9 is —OMet (—OCH 3 ), and R 11 is trifluormethyl (—CF 3 ).

7. A method for treating an immune disease in a subject in need thereof, the method comprising the step of administering to the subject a therapeutically effective amount of a compound according to claim 1 .

8. A combination comprising (a) a compound according to claim 1 , and (b) a second compound that is effective in the treatment of sepsis or systemic inflammation.

9. The combination according to claim 8 , wherein the second compound (b) that is effective in the treatment of sepsis or systemic inflammation is selected from another PPARγ antagonist, an immune suppressive agent, an antibiotic, a vasopressor, a corticosteroids, or activated protein C.

10. A method for treating an immune disease in a subject in need thereof, the method comprising the step of administering to the subject a therapeutically effective amount of the combination according to claim 8 .

11. A pharmaceutical composition, comprising a compound according to claim 1 , or a combination according to claim 10 , together with a pharmaceutically acceptable carrier, adjuvant, diluent and/or excipient.

12. The method according to claim 7 , wherein the immune disease is systemic inflammation or sepsis.

13. The compound according to claim 1 , wherein R 3 is non-substituted C 2 -C 6 alkyl.

14. The compound according to claim 1 , wherein R 3 is non-substituted straight C 4 alkyl.

15. The compound according to claim 6 , wherein the compound is (E)-2-(5-((4-methoxy-2-(trifluoromethyl)quinolin-6-yl)methoxy)-2-((4-(trifluoromethyl) benzyl)oxy)-benzylidene) hexanoic acid (MTTB).