Novel compounds, their preparation and use

Abstract

Novel compounds of the general formula (I), the use of these compounds as pharmaceutical compositions, pharmaceutical compositions comprising the compounds and methods of treatment employing these compounds and compositions. The present compounds may be useful in the treatment and/or prevention of conditions mediated by Peroxisome Proliferator-Activated Receptors (PPAR), in particular the PPARδ suptype.

1 . A compound of the general formula (I):  
       
         
           
           
               
               
           
         
         wherein X 1  is aryl or heteroaryl each of which is optionally substituted with one or more substituents selected from 
 halogen, hydroxy, cyano, amino or carboxy; or  
 C 1-6 -alkyl, C 3-6 -cycloalkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, aryl, aralkyl, heteroaryl, heteroaralkyl, C 1-6 -alkoxy, C 3-6 -cycloalkoxy, aryloxy, aralkoxy, heteroaralkoxy, C 1-6 -alkylthio, arylthio, C 3-6 -cycloalkylthio, C 1-6 -alkylcarbonyl, arylcarbonyl, C 1-6 -alkylsulfonyl, arylsulfonyl, C 1-6 -alkylsulfonyloxy, arylsulfonyloxy, C 1-6 -alkylamido, arylamido, C 1-6 -alkylaminocarbonyl, C 1-6 -alkylamino, C 1-6 -dialkylamino or C 3-6 -cycloalkylamino each of which is optionally substituted with one or more halogens; and  
 
         X 2  is arylene or heteroarylene each of which is optionally substituted with one or more substituents selected from 
 halogen, hydroxy, cyano, amino or carboxy; or  
 C 1-6 -alkyl, C 3-6 -cycloalkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 1-6 -alkoxy, C 3-6 -cycloalkoxy, C 1-6 -alkylthio, C 3-6 -cycloalkylthio, C 1-6 -alkylamino, C 1-6 -dialkylamino or C 3-6 -cycloalkylamino each of which is optionally substituted with one or more halogens; and  
 
         X 3  is aryl or heteroaryl each of which is optionally substituted with one or more substituents selected from 
 halogen, hydroxy, cyano, amino or carboxy; or  
 C 1-6 -alkyl, C 3-6 -cycloalkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, aralkyl, heteroaralkyl, C 1-6 -alkoxy, C 3-6 -cycloalkoxy, aryloxy, aralkoxy, heteroaralkoxy, C 1-6 -alkylthio, arylthio, C 3-6 -cycloalkylthio, C 1-6 -alkylcarbonyl, arylcarbonyl, C 1-6 -alkylsulfonyl, arylsulfonyl, C 1-6 -alkylsulfonyloxy, arylsulfonyloxy, C 1-6 -alkylamido, arylamido, C 1-6 -alkylaminocarbonyl, C 1-6 -alkylamino, C 1-6 -dialkylamino or C 3-6 -cycloalkylamino each of which is optionally substituted with one or more halogens; and  
 
         Ar is arylene which is optionally substituted with one or more substituents selected from 
 halogen, hydroxy or cyano; or  
 C 1-6 -alkyl, C 3-6 -cycloalkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, C 1-6 -alkoxy, C 3-6 -cycloalkoxy, aryloxy, aralkoxy, heteroaralkoxy, C 1-6 -alkylthio, arylthio or C 3-6 -cycloalkylthio each of which is optionally substituted with one or more halogens; and  
 
         Y 1  is O or S; and  
         Y 2  is O or S; and  
         Z is —(CH 2 ) n — wherein n is 1, 2 or 3; and  
         R 1  is hydrogen, halogen or a substituent selected from 
 C 1-6 -alkyl, C 3-6 -cycloalkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, aralkyl, heteroaralkyl, C 1-6 -alkoxy, C 3-6 -cycloalkoxy, aryloxy, aralkoxy, heteroaralkoxy, C 1-6 -alkylthio, arylthio or C 3-6 -cycloalkylthio each of which is optionally substituted with one or more halogens; and  
 
         R 2  is hydrogen, C 1-6 -alkyl, C 3-6 -cycloalkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 4-6 -alkenynyl or aryl; or  
         a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, tautomeric form, stereoisomer, mixture of stereoisomers, racemic mixture, or polymorphs thereof.  
       
     
     
         2 . A compound according to  claim 1 , wherein X 1  is aryl or heteroaryl optionally substituted with one or more substituents selected from 
 halogen; or    C 1-6 -alkyl, aryl, C 1-6 -alkoxy, C 1-6 -alkylsulfonyl or C 1-6 -alkylsulfonyloxy each of which is optionally substituted with one or more halogens.    
     
     
         3 . A compound according to  claim 2 , wherein X 1  is phenyl, furyl, thienyl, benzothienyl or benzofuranyl optionally substituted with one or more substituents selected from 
 halogen; or    C 1-6 -alkyl, aryl, C 1-6 -alkoxy, C 1-6 -alkylsulfonyl or C 1-6 -alkylsulfonyloxy each of which is optionally substituted with one or more halogens.    
     
     
         4 . A compound according to  claim 3 , wherein X 1  is phenyl optionally substituted with one or more substituents selected from halogen, C 1-6 -alkyl, aryl or perhalomethyl.  
     
     
         5 . A compound according to  claim 4 , wherein X 1  is phenyl optionally substituted with one or more substituents seleced from phenyl or trifluoromethyl.  
     
     
         6 . A compound according to  claim 5 , wherein X, is phenyl.  
     
     
         7 . A compound according to  claim 3 , wherein X, is furyl, thienyl, benzothienyl or benzofuranyl with one or more substituents seleced from halogen, C 1-6 -alkyl, aryl or perhalomethyl.  
     
     
         8 . A compound according to  claim 7 , wherein X 1  is furyl optionally substituted with one or more substituents seleced from halogen, C 1-6 -alkyl, phenyl or trifluoromethyl.  
     
     
         9 . A compound according to  claim 7 , wherein X 1  is thienyl optionally substituted with one or more substituents seleced from halogen, C 1-6 -alkyl, phenyl or trifluoromethyl.  
     
     
         10 . A compound according to  claim 7 , wherein X 1  is benzothienyl optionally substituted with one or more substituents seleced from halogen, C 1-6 -alkyl, phenyl or trifluoromethyl.  
     
     
         11 . A compound according to  claim 1 , wherein X 2  is arylene or heteroarylene optionally substituted with one or more substituents selected from 
 halogen; or    C 1-6 -alkyl or C 1-6 -alkoxy each of which is optionally substituted with one or more halogens.    
     
     
         12 . A compound according to  claim 11 , wherein X 2  is phenylene optionally substituted with one or more substituents selected from 
 halogen; or    C 1-6 -alkyl or C 1-6 -alkoxy each of which is optionally substituted with one or more halogens.    
     
     
         13 . A compound according to  claim 12 , wherein X 2  is phenylene optionally substituted with one or more halogens.  
     
     
         14 . A compound according to  claim 13 , wherein X 2  is phenylene.  
     
     
         15 . A compound according to  claim 11 , wherein X 2  is benzofuranylene optionally substituted with one or more substituents selected from 
 halogen; or    C 1-6 -alkyl or C 1-6 -alkoxy each of which is optionally substituted with one or more halogens.    
     
     
         16 . A compound according to  claim 15 , wherein X 2  is benzofuranylene optionally substituted with C 1-6 -alkyl.  
     
     
         17 . A compound according to  claim 1 , wherein X 3  is aryl or heteroaryl optionally substituted with one or more substituents selected from 
 halogen; or    C 1-6 -alkyl, C 1-6 -alkoxy, C 1-6 -alkylsulfonyl or C 1-6 -alkylsulfonyloxy each of which is optionally substituted with one or more halogens.    
     
     
         18 . A compound according to  claim 17 , wherein X 3  is phenyl, furyl, thienyl, benzothienyl or benzofuranyl optionally substituted with one or more substituents selected from 
 halogen; or    C 1-6 -alkyl, C 1-6 -alkoxy, C 1-6 -alkylsulfonyl or C 1-6 -alkylsulfonyloxy each of which is optionally substituted with one or more halogens.    
     
     
         19 . A compound according to  claim 18 , wherein X 3  is phenyl optionally substituted with one or more halogens.  
     
     
         20 . A compound according to  claim 18 , wherein X 3  is phenyl optionally substituted with one or more substituents selected from C 1-6 -alkyl or perhalomethyl.  
     
     
         21 . A compound according to  claim 18 , wherein X 3  is phenyl.  
     
     
         22 . A compound according to  claim 18 , wherein X 3  is furyl, thienyl, benzothienyl or benzofuranyl optionally substituted with one or more substituents selected from halogen, C 1-6 -alkyl or perhalomethyl.  
     
     
         23 . A compound according to  claim 22 , wherein X 3  is furyl optionally substituted with one or more substituents selected from halogen, C 1-6 -alkyl or trifluoromethyl.  
     
     
         24 . A compound according to  claim 22 , wherein X 3  is thienyl optionally substituted with one or more substituents selected from halogen, C 1-6 -alkyl or trifluoromethyl.  
     
     
         25 . A compound according to  claim 22 , wherein X 3  is benzothienyl optionally substituted with one or more substituents selected from halogen, C 1-6 -alkyl or trifluoromethyl.  
     
     
         26 . A compound according to  claim 22 , wherein X 3  is benzofuranyl optionally substituted with one or more substituents selected from halogen, C 1-6 -alkyl or trifluoromethyl.  
     
     
         27 . A compound according to  claim 1 , wherein Ar is phenylene which is optionally substituted with one or more substituents selected from 
 halogen, hydroxy or cyano; or    C 1-6 -alkyl, C 3-6 -cycloalkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, C 1-6 -alkoxy, C 3-6 -cycloalkoxy, aryloxy, aralkoxy, heteroaralkoxy, C 1-6 -alkylthio, arylthio or C 3-6 -cycloalkylthio each of which is optionally substituted with one or more halogens.    
     
     
         28 . A compound according to  claim 27 , wherein Ar is phenylene which is optionally substituted with one or more substituents selected from halogen; or 
 C 1-6 -alkyl, C 1-6 -alkoxy, aryloxy or aralkoxy each of which is optionally substituted with one or more halogens.    
     
     
         29 . A compound according to  claim 28 , wherein Ar is phenylene which is optionally substituted with methyl.  
     
     
         30 . A compound according to  claim 29 , wherein Ar is phenylene.  
     
     
         31 . A compound according to  claim 1 , wherein Y 1  is S.  
     
     
         32 . A compound according to  claim 1 , wherein Y 2  is O.  
     
     
         33 . A compound according to  claim 1 , wherein n is 1.  
     
     
         34 . A compound according to  claim 1 , wherein R 1  is hydrogen or a substituent selected from C 1-6 -alkyl, aralkyl, C 1-6 -alkoxy, aryloxy, aralkoxy each of which is optionally substituted with one or more halogens.  
     
     
         35 . A compound according to  claim 34 , wherein R 1  is hydrogen or a substituent selected from C 1-6 -alkyl or C 1-6 alkoxy each of which is optionally substituted with one or more halogens.  
     
     
         36 . A compound according to  claim 35 , wherein R 1  is hydrogen.  
     
     
         37 . A compound according to  claim 1 , wherein R 2  is hydrogen.  
     
     
         38 . A compound according to  claim 1 , wherein R 2  is methyl or ethyl.  
     
     
         39 . A compound according to  claim 1 , which is selected from the following: 
 (E/Z) {4-[3-Biphenyl-4-yl-3-(4-bromo-phenyl)-allylsulfanyl]-phenoxy}-acetic acid, and    (E/Z) {4-[3-(4-Bromo-phenyl)-3-(3′-trifluoromethyl-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid; or    a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, tautomeric form, stereoisomer, mixture of stereoisomers, racemic mixture, or polymorphs thereof.    
     
     
         40 . A compound according to  claim 1 , which is selected from the following: 
 {4-[3-(4-Bromo-phenyl)-3-[1,1′;4′,1″]terphenyl-4″-yl-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (E/Z)-[2-Methyl-4-[3-[5-(5-methylthiophen-2-yl)benzo[b]furan-2-yl]-3-(thiophen-2-yl)allylsulfanyl]phenoxy]acetic acid;    (E/Z)-[4-[3-(Biphenyl-4-yl)-3-(furan-2-yl)allylsultanyl]-2-methylphenoxy]acetic acid;    (E/Z)-[4-[3-(Benzo[b]thiophen-3-yl)-3-(biphenyl-4-yl)allylsulfanyl]-2-methylphenoxy]acetic acid;    [4-[(3-Benzo[b]thiophen-2-yl)-3-(biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy]-acetic acid; and    (E/Z)-[4-[3-(4-Biphenylyi)-3-(5-methylthiophen-2-yl)allylsulfanyl]-2-methylphenoxy]acetic acid;    or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, tautomeric form, stereoisomer, mixture of stereoisomers, racemic mixture, or polymorphs thereof.    
     
     
         41 . A compound according to  claim 1 , which is selected from the following: 
 (E) {4-[3-Biphenyl-4-yl-3-(2-fluoro-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (Z) {4-[3-Biphenyl-4-yl-3-(2-fluoro-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (E) {4-[3-Biphenyl-4-yl-3-(2-chloro-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (Z) {4-[3-Biphenyl-4-yl-3-(2-chloro-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (E) {4-[3-Biphenyl-4-yl-3-(2-bromo-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (Z) {4-[3-Biphenyl-4-yl-3-(2-bromo-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (E) {4-[3-Biphenyl-4-yl-3-(2-iodo-phenyl)-allylsulfanyl]-phenoxy)-acetic acid;    (Z) {4-[3-Biphenyl-4-yl-3-(2-iodo-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (E) {4-[3-Biphenyl-4-yl-3-(2-methoxy-phenyl)-allysulfanyl]-phenoxy}-acetic acid;    (Z) {4-[3-Biphenyl-4-yl-3-(2-methoxy-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (E) {4-[3-Biphenyl-4-yl-3-(2-trifluoromethoxy-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (Z) {4-[3-Biphenyl-4-yl-3-(2-trifluoromethoxy-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (E) {4-[3-Biphenyl-4-yl-3-(2-methyl-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (Z) {4-[3-Biphenyl-4-yl-3-(2-methyl-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (E) {4-[3-Biphenyl-4-yl-3-(2-trifluoromethyl-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (Z) {4-[3-Biphenyl-4-yl-3-(2-trifluoromethyl-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (E) {4-[3-Biphenyl-4-yl-3-(3-fluoro-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (Z) {4-[3-Biphenyl-4-yl-3-(3-fluoro-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (E) {4-[3-Biphenyl-4-yl-3-(3-chloro-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (Z) {4-[3-Biphenyl-4-yl-3-(3-chloro-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (E) {4-[3-Biphenyl-4-yl-3-(3-bromo-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (Z) {4-[3-Biphenyl-4-yl-3-(3-bromo-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (E) {4-[3-Biphenyl-4-yl-3-(3-iodo-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (Z) {4-[3-Biphenyl-4-yl-3-(3-iodo-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (E) {4[3-Biphenyl-4-yl-3-(3-methoxy-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (Z) {4-[3-Biphenyl-4-yl-3-(3-methoxy-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (E) {4-[3-Biphenyl-4-yl-3-(3-trifluoromethoxy-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (Z) {4-[3-Biphenyl-4-yl-3-(3-trifluoromethoxy-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (E) {4-[3-Biphenyl-4-yl-37(3-methyl-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (Z) {4-[3-Biphenyl-4-yl-3-(3-methyl-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (E) {4-[3-Biphenyl-4-yl-3-(3-trifluoromethyl-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (Z) {4-[3-Biphenyl-4-yl-3-(3-trifluoromethyl-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (E) {4-[3-Biphenyl-4-yl-3-(4-fluoro-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (Z) {4-[3-Biphenyl-4-yl-3-(4-fluoro-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (E) {4-[3-Biphenyl-4-yl-3-(4-chloro-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (Z) {4-[3-Biphenyl-4-yl-3-(4-chloro-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (E/Z) {4-[3-Biphenyl-4-yl-3-(4-bromo-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (E) {4-[3-Biphenyl-4-yl-3-(4-bromo-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (Z) {4-[3-Biphenyl-4-yl-3-(4-bromo-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (E) {4-[3-Biphenyl-4-yl-3-(4-iodo-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (Z) {4-[3-Biphenyl-4-yl-3-(4-iodo-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (E) {4-[3-Biphenyl-4-yl-3-(4-methoxy-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (Z) {4-[3-Biphenyl-4-yl-3-(4-methoxy-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (E) {4-[3-Biphenyl-4-yl-3-(4-trifluoromethoxy-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (Z) {4-[3-Biphenyl-4-yl-3-(4-trifluoromethoxy-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (E) {4-[3-Biphenyl-4-yl-3-(4-methyl-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (Z) {4-[3-Biphenyl-4-yl-3-(4-methyl-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (E) {4-[3-Biphenyl-4-ya-3-(4-trifluoromethyl-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (Z) {4-[3-Biphenyl-4-yl-3-(4-trifluoromethyl-phenyl)-allylsulfanyl]-phenoxy}-acetic acid;    (E) {4-[3-(4-Fluoro-phenyl)-3-(2′-trifluoromethyl-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (Z) {4-[3-(4-Fluoro-phenyl)-3-(2′-trifluoromethyl-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (E/Z) {4-[3-(4-Fluoro-phenyl)-3-(3′-trifluoromethyl-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (E) {4-[3-(4-Fluoro-phenyl)-3-(3′-trifluoromethyl-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (Z) {4-[3-(4-Fluoro-phenyl)-3-(3′-trifluoromethyl-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (E) {4-[3-(4-Fluoro-phenyl)-3-(4′-trifluoromethyl-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (Z) {4-[3-(4-Fluoro-phenyl)-3-(4′-trifluoromethyl-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (E) {4-[3-(4-Fluoro-phenyl)-3-(3′-chloro-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (Z) {4-[3-(4-Fluoro-phenyl)-3-(3′-chloro-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (E) {4-[3-(4-Fluoro-phenyl)-3-(4′-chloro-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (Z) {4-[3-(4-Fluoro-phenyl)-3-(4′-chloro-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (E) {4-[3-(4-Fluoro-phenyl)-3-(3′-methoxy-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (Z) {4-[3-(4-Fluoro-phenyl)-3-(3′-methoxy-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (E) {4-[3-(4-Fluoro-phenyl)-3-(4′-methoxy-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (Z) {4-[3-(4-Fluoro-phenyl)-3-(4′-methoxy-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (E) {4-[3-(4-Chloro-phenyl)-3-(2′-trifluoromethyl-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (Z) {4-[3-(4-Chloro-phenyl)-3-(2′-trifluoromethyl-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (E/Z) {4-[3-(4-Chloro-phenyl)-3-(3′-trifluoromethyl-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (E) {4-[3-(4-Chloro-phenyl)-3-(3′-trifluoromethyl-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (Z) {4-[3-(4-Chloro-phenyl)-3-(3′-trifluoromethyl-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (E) {4-[3-(4-Chloro-phenyl)-3-(4′-trifluoromethyl-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (Z) {4-[3-(4-Chloro-phenyl)-3-(4′-trifluoromethyl-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (E) {4-[3-(4-Chloro-phenyl)-3-(3′-chloro-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (Z) {4-[3-(4-Chloro-phenyl)-3-(3′-chloro-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (E) {4-[3-(4-Chloro-phenyl)-3-(4′-chloro-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (Z) {4-[3-(4-Chloro-phenyl)-3-(4′-chloro-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (E) {4-[3-(4-Chloro-phenyl)-3-(3′-methoxy-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (Z) {4-[3-(4-Chloro-phenyl)-3-(3′-methoxy-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (E) {4-[3-(4-Chloro-phenyl)-3-(4′-methoxy-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (Z) {4-[3-(4-Chloro-phenyl)-3-(4′-methoxy-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (E) {4-[3-(4-Bromo-phenyl)-3-(2′-trifluoromethyl-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (Z) {4-[3-(4-Bromo-phenyl)-3-(2′-trifluoromethyl-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (E/Z) {4-[3-(4-Bromo-phenyl)-3-(3′-trifluoromethyl-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (E) {4-[3-(4-Bromo-phenyl)-3-(3′-trifluoromethyl-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (Z) {4-[3-(4-Bromo-phenyl)-3-(3′-trifluoromethyl-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (E) {4-[3-(4-Bromo-phenyl)-3-(4′-trifluoromethyl-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (Z) {4-[3-(4-Bromo-phenyl)-3-(4′-trifluoromethyl-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (E) {4-[3-(4-Bromo-phenyl)-3-(3′-chloro-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (Z) {4-[3-(4-Bromo-phenyl)-3-(3′-chloro-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (E) {4-[3-(4-Bromo-phenyl)-3-(4′-chloro-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (Z) {4-[3-(4-Bromo-phenyl)-3-(4′-chloro-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (E) {4-[3-(4-Bromo-phenyl)-3-(3′-methoxy-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (Z) {4-[3-(4-Bromo-phenyl)-3-(3′-methoxy-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid;    (E) {4-[3-(4-Bromo-phenyl)-3-(4′-methoxy-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid; and    (Z) {4-[3-(4-Bromo-phenyl)-3-(4′-methoxy-biphenyl-4-yl)-allylsulfanyl]-2-methyl-phenoxy}-acetic acid; or    a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, tautomeric form, stereoisomer, mixture of stereoisomers, racemic mixture, or polymorphs thereof.    
     
     
         42 . A compound according to  claim 1 , which is a PPARδ agonist.  
     
     
         43 . A compound according to  claim 42 , which is a selective PPARδ agonist.  
     
     
         44 . A pharmaceutical composition comprising, as an active ingredient, at least one compound according to  claim 1 , together with one or more pharmaceutically acceptable carriers or excipients.  
     
     
         45 . A pharmaceutical composition according to  claim 44  in unit dosage form, comprising from about 0.05 mg to about 1000 mg, preferably from about 0.1 to about 500 mg of and especially preferred from about 0.5 mg to about 200 mg per day of compound according to  claim 1 .  
     
     
         46 . A pharmaceutical composition for the treatment and/or prevention of conditions mediated by nuclear receptors, in particular the Peroxisome Proliferator-Activated Receptors (PPAR), the composition comprising a compound according to  claim 1  together with one or more pharmaceutically acceptable carriers or excipients.  
     
     
         47 . A pharmaceutical composition for the treatment and/or prevention of type I diabetes, type II diabetes, impaired glucose tolerance, insulin resistance or obesity comprising a compound according to  claim 1  together with one or more pharmaceutically acceptable carriers or excipients.  
     
     
         48 . A pharmaceutical composition according to any one of the  claim 44  for oral, nasal, transdermal, pulmonal, or parenteral administration.  
     
     
         49 . A method for the treatment and/or prevention of conditions mediated by nuclear receptors, in particular the Peroxisome Proliferator-Activated Receptors (PPAR), the method comprising administering to a subject in need thereof an effective amount of a compound according to  claim 1  or a pharmaceutical composition comprising the same.  
     
     
         50 . A method for the treatment and/or prevention of type I diabetes, type II diabetes, impaired glucose tolerance, insulin resistance or obesity, the method comprising administering to a subject in need thereof an effective amount of a compound according to  claim 1  or of a pharmaceutical composition comprising the same.  
     
     
         51 . The method according to  claim 49  wherein the effective amount of the compound according to  claim 1  is in the range of from about 0.05 mg to about 1000 mg, preferably from about 0.1 to about 500 mg of and especially preferred from about 0.5 mg to about 200 mg per day.  
     
     
         52 . The method according to  claim 50  wherein the effective amount of the compound according to  claim 1  is in the range of from about 0.05 mg to about 1000 mg, preferably from about 0.1 to about 500 mg of and especially preferred from about 0.5 mg to about 200 mg per day.