PPAR agonist compounds, preparation and uses

1. A compound of formula:

in which,

G represents:

a radical —OR a , —SR a , or

a radical —NR a R b ,

R a being selected from an alkyl radical with 1 to 6 carbon atoms or alkenyl radical with 2 to 6 carbon atoms, a ring with 3 to 14 atoms, a phenyl radical, a phenylalkyl radical with the alkyl moiety having 1 to 3 carbon atoms;

R b being selected from a hydrogen atom, an alkyl radical with 1 to 6 carbon atoms or alkenyl radical with 2 to 6 carbon atoms, a ring with 3 to 14 atoms, a phenyl radical, or a phenylalkyl radical with the alkyl moiety having 1 to 3 carbon atoms; or

R a and R b can form, together and with the nitrogen atom to which they are bound, a heterocycle with 3 to 8 atoms.

R 1 and R 2 , which may be identical or different, represent a hydrogen atom or an alkyl radical with 1 to 6 carbon atoms or alkenyl radical with 2 to 6 carbon atoms; or

R 1 and R 2 can form, together and with the carbon atom to which they are bound, a carbocycle with 3 to 6 carbon atoms;

Y 1 represents:

a oxygen atom or sulfur atom, or

a group —NR—, in which R has the same definition as R b ;

Y 2 represents:

a oxygen atom or sulfur atom, or

a radical —CR 5 R 6 —; with R 5 and R 6 , which may be identical or different, selected from a hydrogen atom or halogen atom, an alkyl radical with 1 to 6 carbon atoms or an alkenyl or alkynyl radical with 2 to 6 carbon atoms, a ring with 3 to 6 atoms, a phenyl radical, a phenylalkyl radical with the alkyl moiety having 1 to 3 carbon atoms;

X 1 , X 2 , X 3 represent independently a hydrogen atom or halogen atom, an alkyl radical with 1 to 6 carbon atoms or alkenyl radical with 2 to 6 carbon atoms, a group —OR′ a , —SR′ a , —NR′ a R′ b , a ring with 5 to 14 atoms, or a phenylalkyl radical with the alkyl moiety having 1 to 3 carbon atoms,

with at least one of the groups X 1 , X 2 and X 3 different from a hydrogen atom and from a halogen atom;

R′ a and R′ b , which may be identical or different, having the same definitions as R a and R b ;

X 4 and X 5 represent independently a hydrogen atom or halogen atom, an alkyl radical with 1 to 6 carbon atoms or alkenyl radical with 2 to 6 carbon atoms, a group —OR″ a , —SR″ a or —NR″ a R″ b , a ring with 3 to 14 atoms, a phenyl radical, or a phenylalkyl radical with the alkyl moiety having 1 to 3 carbon atoms;

R″ a and R″ b , which may be identical or different, having the same definitions as R a and R b ;

R 3 and R 4 , which may be identical or different, represent a hydrogen atom or halogen atom, an alkyl radical with 1 to 6 carbon atoms or alkenyl radical with 2 to 6 carbon atoms, a ring with 3 to 14 atoms, a phenyl radical, or a phenylalkyl radical with the alkyl moiety having 1 to 3 carbon atoms;

W represents:

a carboxyl radical —COOH; or

a function derived from the carboxylic acid function, selected from —COOR′″ a , —COSR′″ a , —CONR′″ a R′″ b , —CSNR′″ a R′″ b , —CONH 2 ; or

a bioisosteric group of the carboxyl radical, selected from:

an acylsulfonamide radical (—CONHSO 2 R′″ a );

a hydrazide radical (—CONHNR′″ a R′″ b );

a radical selected from the thiazolidinedione, oxazolidinedione, tetrazole, oxadiazolone, triazolone, triazole, 3-alkyltriazole, or imidazolidinedione rings;

R′″ a and R″′ b , which may be identical or different, having the same definitions as R a and R b .

2. The compound of claim 1 , wherein Y 2 is positioned para or meta of Y 1 .

3. The compound of claim 1 , wherein:

X 3 denotes a hydrogen atom, and/or

X 4 and X 5 denote independently a hydrogen atom, an alkyl radical having 1 to 6 carbon atoms, a group —OR″ a or —SR″ a ; R″ a being an alkyl radical having 1 to 6 carbon atoms, and optionally wherein

Y 2 is positioned para or meta of Y 1 .

4. The compound of claim 1 , wherein R 1 , R 2 , R 3 , R 4 denote independently a hydrogen atom or a methyl, ethyl, propyl, butyl, isopropyl or tert-butyl radical.

5. The compound of claim 1 , wherein X 3 , R 1 and R 2 denote hydrogen atoms.

6. The compound of claim 1 , wherein X 1 and/or X 2 denote a ring with 5 to 10 atoms, unsubstituted or substituted with a —CF 3 group.

7. The compound of claim 1 , wherein G denotes

a radical —OR a or —SR a , with R a selected from alkyl radical having 1 to 6 carbon atoms, a cyclohexyl or a phenyl radical; or

a radical —NR a R b , R a and R b forming together, and with the nitrogen atom to which they are bound, a heterocycle with 3 to 8 atoms.

8. The compound of claim 1 , wherein G denotes a radical —OR a with R a selected from a methyl, ethyl, propyl, butyl, isopropyl or tert-butyl radical.

9. The compound of claim 7 , wherein:

X 2 and X 3 denote simultaneously a hydrogen atom; or

X 3 and X 1 denote simultaneously a hydrogen atom.

10. The compound of claim 1 , characterized in that Y 1 denotes an oxygen or sulfur atom, and simultaneously Y 2 denotes an oxygen atom, a sulfur atom, or a group —CR 5 R 6 .

11. The compound of claim 1 , characterized in that Y 1 denotes a group —NR and simultaneously Y 2 denotes an oxygen atom, a sulfur atom or a group —CR 5 R 6 .

12. The compound of claim 10 , characterized in that X 1 denotes an unsubstituted phenyl radical or a phenyl radical substituted with a group —CF 3 , and/or G denotes a group —OCH 3 or —OC(CH 3 ) 3 .

13. The compound of claim 1 , wherein it is selected from:

Cpd 1: 2-(4-((2-methoxy-6-phenylpyridin-3-yl)methoxy)phenoxy)-2-methyl-propanoic acid

Cpd 2: 2-(4-((2-methoxy-6-phenylpyridin-3-yl)methoxy)phenoxy)ethanoic acid

Cpd 3: 2-(4-((2-methoxy-6-phenylpyridin-3-yl)methoxy)phenoxy)propanoic acid

Cpd 4: 2-(4-(((2-methoxy-6-phenylpyridin-3yl)methyl)amino)phenoxy)ethanoic acid

Cpd 5: 2-(4-(((2-methoxy-6-phenylpyridin-3yl)methyl)amino)phenoxy)propanoic acid

Cpd 6: 2-(4-((2-tert-butyloxy-6-phenylpyridin-3-yl)methoxy)phenoxy)-2-methyl-propanoic acid

Cpd 7: 2-(4-(((2-tert-butyloxy-6-phenylpyridin-3-yl)methoxy)phenoxy)ethanoic acid

Cpd 8: 2-(4-((2-tert-butyloxy-6-phenylpyridin-3-yl)methyl)amino) phenoxy)ethanoic acid

Cpd 9: 2-(4-(((2-tert-butyloxy-6-phenylpyridin-3-yl)methyl)amino)phenoxy)-2-methyl-propanoic acid

Cpd 10: 2-(4-(((2-tert-butyloxy-6-phenylpyridin-3-yl)methyl)amino)phenoxy)-propanoic acid

Cpd 11: 2-(4-(((2-methoxy-6-phenylpyridin-3-yl)methyl)amino)phenylthio)-2-methyl-propanoic acid

Cpd 12: 2-(4-(((2-methoxy-6-phenylpyridin-3-yl)methyl)amino)phenoxy)-2-methyl-propanoic acid

Cpd 13: 2-(3-(((2-methoxy-6-phenylpyridin-3-yl)methyl)amino)phenoxy)-2-methyl-propanoic acid

Cpd 14: 2-(3-(((2-methoxy-6-phenylpyridin-3-yl)methyl)amino)phenoxy)ethanoic acid

Cpd 15: 2-(4-((2-hexyloxy-6-phenylpyridin-3-yl)methoxy)phenoxy)ethanoic acid

Cpd 16: 2-(4-(((2-methoxy-6-phenylpyridin-3-yl)methyl)amino)phenylthio)-ethanoic acid

Cpd 17: 2-(4-((2-hexyloxy-6-phenylpyridin-3-yl)methoxy)phenoxy)-2-methyl-propanoic acid

Cpd 18: 2-(4-((2-cyclohexyloxy-6-phenylpyridin-3-yl)methoxy)phenoxy)ethanoic acid

Cpd 19: 3-(4-(((2-methoxy-6-phenylpyridin-3-yl)methyl)amino)phenyl)propanoic acid

Cpd 20: 2-(4-((6-phenyl-2-(piperidin-1-yl)pyridin-3-yl)methoxy)phenoxy)-ethanoic acid

Cpd 21: 2-(4-((2-methoxy-6-(4-(trifluoromethyl)phenyl)pyridin-3-yl)methoxy)-phenoxy)-2-methylpropanoic acid

Cpd 22: 2-(4-(((2-methoxy-6-(4-(trifluoromethyl)phenyl)pyridin-3-yl)methyl)amino)-phenylthio)-2-methylpropanoic acid

Cpd 23: 2-(4-(((2-methoxy-6-(4-(trifluoromethyl)phenyl)pyridin-3-yl)methyl)amino)-phenylthio)ethanoic acid

Cpd 24: 2-(4-((2-methoxy-6-(4-(trifluoromethyl)phenyl)pyridin-3-yl)methoxy)-phenoxy)ethanoic acid

Cpd 25: 2-(4-((2-phenylthio-6-(phenyl)pyridin-3-yl)methoxy)phenoxy)ethanoic acid

Cpd 26: 2-(4-(((2-methoxy-5-phenylpyridin-3-yl)methyl)amino)phenylthio)-ethanoic acid

Cpd 27: 2-(4-(((2-methoxy-6-phenylpyridin-3-yl)methyl)amino)phenylthio)-2,2-difluoroethanoic acid

Cpd 28: 2-(4-(((2-methoxy-5,6-diphenylpyridin-3-yl)methyl)amino)phenylthio)-ethanoic acid

Cpd 29: 2-(4-(((2-methoxy-5-bromo-6-phenylpyridin-3-yl)methyl)amino)-phenylthio)-ethanoic acid

Cpd 30: 2-(4-(((2-methoxy-6-furylpyridin-3-yl)methyl)amino)phenylthio)ethanoic acid

Cpd 31: 3-(4-(((2-methoxy-6-furylpyridin-3-yl)methyl)amino)phenyl)propanoic acid

Cpd 32: 2-(4-(((2-methoxy-6-phenylpyridin-3-yl)methyl)amino)phenylthio)-2-phenyl-ethanoic acid

Cpd 33: 3-(4-(((2-methoxy-6-phenylpyridin-3-yl)methyl)(methyl)amino)phenyl)-propanoic acid

Cpd 34: 3-(4-(1-((2-methoxy-6-phenylpyridin-3-yl)propyl)amino)phenyl)propanoic acid

Cpd 35: 2-(4-(((2-methoxy-6-phenylpyridin-3-yl)methyl)amino)-2,6-dimethyl-phenoxy)ethanoic acid

Cpd 36: 3-(4-(((2-methoxy-6-(4-(trifluoromethyl)phenyl)pyridin-3-yl)methyl)amino)-phenyl)-propanoic acid

Cpd 37: 3-(4-((2-methoxy-6-phenylpyridin-3-yl)methylthio)phenyl)propanoic acid

Cpd 38: 3-(4-(((2-(ethylthio)-6-phenylpyridin-3-yl)methyl)amino)phenyl)-propanoic acid

Cpd 39: 3-(4-(((2-methoxy-6-(parabiphenyl)pyridin-3-yl)methyl)amino)phenyl)-propanoic acid

Cpd 40: 3-(4-(((2-methoxy-6-(3-(trifluoromethyl)phenyl)pyridin-3-yl)methyl)-amino)-phenyl)propanoic acid

Cpd 41: 3-(4-(((2-methoxy-5-phenylpyridin-3-yl)methyl)amino)phenyl)propanoic acid

Cpd 42: 3-(4-((2(-methoxy-6-phenylpyridin-3-yl)methyl)amino)phenyl)-3-phenyl-propanoic acid

Cpd 43: 3-(2-methoxy-4-(((2-methoxy-6-phenylpyridin-3-yl)methyl)amino)-phenyl)-propanoic acid

Cpd 44: 3-(3-methoxy-4-(((2-methoxy-6-phenylpyridin-3-yl)methyl)amino)-phenyl)-propanoic acid

Cpd 45: 3-(4-(((2-methoxy-6-phenylpyridin-3-yl)methyl)amino)phenyl)butanoic acid

Cpd 46: 3-(4-(((2-methoxy-5-(4-(trifluoromethyl)phenyl)pyridin-3-yl)methyl)-amino)phenyl)propanoic acid

Cpd 47: 3-(4-(((2-methoxy-5-(3-(trifluoromethyl)phenyl)pyridin-3-yl)methyl)-amino)-phenyl)propanoic acid

Cpd 48: 3-(4-(((2,6-dimethoxy-5-phenylpyridin-3-yl)methyl)amino)phenyl)-propanoic acid

Cpd 49: 3-(4-(((5-(4-chlorophenyl)-2-methoxypyridin-3-yl)methyl)amino)phenyl)-propanoic acid

Cpd 50: 3-(4-(((2-methoxy-5-(naphthalen-2-yl)pyridin-3-yl)methyl)amino)phenyl)-propanoic acid

Cpd 51: 3-(4-(((2-ethoxy-6-phenylpyridin-3-yl)methyl)amino)phenyl)propanoic acid

Cpd 52: 3-(4-((2-methoxy-5-phenylpyridin-3-yl)methoxy)phenyl)hex-4-ynoic acid

Cpd 53: 3-(4-((2-methoxy-6-phenylpyridin-3-yl)methoxy)phenyl)hex-4-ynoic acid

Cpd 54: 3-(4-(((2-isopropyloxy-6-phenylpyridin-3-yl)methyl)amino)phenyl)-propanoic acid.

14. A pharmaceutical composition comprising, in a pharmaceutically acceptable carrier, at least one compound as defined in claim 1 , optionally in combination with one or more other therapeutic and/or cosmetic active substances.

15. The pharmaceutical composition of claim 14 for the therapeutic, curative and/or prophylactic treatment of diabetes, dyslipidemias, insulin resistance, pathologies associated with metabolic syndrome, atherosclerosis, cardiovascular diseases, obesity, hypertension and/or inflammatory diseases.

16. A method of therapeutic and/or prophylactic treatment of diabetes, dyslipidemias, insulin resistance, pathologies associated with metabolic syndrome, atherosclerosis, and cardiovascular diseases, obesity, hypertension and/or inflammatory diseases, comprising the administration, to a human subject, of an effective amount of a compound as defined in claim 1 .

17. The compound of claim 12 , characterized in that said group —CF 3 is in para of the pyridinyl radical.