Carboxylic derivates

Abstract

The present invention provides a compound of formula I processes for preparing such compounds, their the utility in treating clinical conditions including lipid disorders (dyslipidemias) whether or not associated with insulin resistance, methods for their therapeutic use and pharmaceutical compositions containing them.

1 . A compound of formula I  
       
         
           
           
               
               
           
         
       
       as well as optical isomers and racemates therof as well as pharmaceutically acceptable salts, prodrugs, solvates and crystalline forms thereof, 
 wherein  
 A is situated in the ortho, meta or para position and represents  
                     
 R is hydrogen; 
 —OR a , wherein R a  represents hydrogen, alkyl, aryl or alkylaryl;  
 —NR a R b , wherein R a  and R b  are the same or different and R a  is as defined above and R b  represents hydrogen, alkyl, aryl, alkylaryl, cyano, —OH, —Oalkyl, —Oaryl, —Oalkylaryl,  
 —COR or —SO 2 R d , wherein R c  represents hydrogen, alkyl, aryl or alkylaryl and R d  represents alkyl, aryl or alkylaryl;  
 
 R 1  is alkyl, aryl, alkenyl, alkynyl, or when A  
                     
  is R 1  can also be cyano; 
 —OR e , wherein R e  is alkyl, acyl, aryl or alkylaryl;  
 —O—[CH 2 ] m —OR f , wherein R f  represents hydrogen, alkyl, acyl, aryl or alkylaryl and m represents an integer 1-8;  
 —OCONR a R c , wherein R a  and R c  are as defined above;  
 —SR d , wherein R d  is as defined above;  
 —SO 2 NR a R f , wherein R f  and R a  are as defined above;  
 —SO 2 OR a , wherein R a  is as defined above;  
 —COOR d , wherein R d  is as defined above;  
 
 R 2  is hydrogen, halogen, alkyl, aryl, or alkylaryl,  
 R 3  and R 4  are the same or different and each represents hydrogen, alkyl, aryl, or alkylaryl;  
 T represents O, S or a single bond;  
 n represents 1, 2, 3 or 4;  
 R 5  and R 6  are independently selected substituents, comprising C, H, N, O, S, Se, P or halogen atoms, which give compounds of the General Formula I a molecular weight <650;  
 with a first proviso that  
 when A is CH 2 CH(OC 2 H 5 )COOC 2 H 5  or CH 2 CH(OC 2 H 5 )COOH; T is O; n is 1 and R 5  represents a C 2-4 alkyl group then R 6  does not represent a group of formula  
                     
 wherein R x  represents chloro, trifluoromethyl or trifluoromethoxy, R y  represents H or fluoro; and a second proviso that when A is CH 2 CH(OC 2 H 5 )COOC 2 H 5  or CH 2 CH(OC 2 H 5 )COOH; T is O; n is 1 and R 5  represents hexyl or heptyl then R 6  does not represent a group of formula  
                     
 wherein R z  represents phenyl, 2,4-difluorophenyl or cyclohexyl, and n is 1 or 2;  
 provided that the compound of formula I is not:  
 (2S)-4-[2-[[2-[[(2,6-dichlorophenyl)methyl]thio]ethyl]amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-[butyl(1-phenylethyl)amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-(α-methoxy-4-[2-oxo-2-[[2-(3-pyridinyl)ethyl]amino]ethoxy]-benzenepropanoic acid;  
 (2S)-α-methyl-4-[2-oxo-2-[[2-(4-phenoxyphenyl)ethyl]amino]ethoxy]-α-phenoxy-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-[(1-methyl-3-phenylpropyl)amino]-2-oxoethoxy]-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-oxo-2-[[2-(4-phenoxyphenyl)ethyl]amino]ethoxy]-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-oxo-2-[4-[4-(trifluoromethyl)phenyl]-1-piperazinyl]ethoxy]-benzenepropanoic acid;  
 (2S)-4-[2-[[2-(4-bromophenyl)ethyl]amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-[[2-[ethyl(3-methylphenyl)amino]ethyl]amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 α-methoxy-α-methyl-4-[2-oxo-2-[[2-(4-phenoxyphenyl)ethyl]amino]ethoxy]-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-[(3-methylbutyl)amino]-2-oxoethoxy]-benzenepropanoic acid;  
 (2S)-4-[2-[4-(diphenylmethyl)-1-piperazinyl]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-(heptylamino)-2-oxoethoxy]-α-methoxy-α-methyl-benzenepropanoic acid;  
 4-[2-[4-(2-fluorophenyl)-1-piperazinyl]-2-oxoethoxy]-α-methoxy-, benzenepropanoic acid;  
 (2S)-4-[2-[4-(4-chlorobenzoyl)-1-piperidinyl]-2-oxoethoxy]-α-methoxy-, benzenepropanoic acid;  
 (2S)-4-[2-[ethyl[(3-methylphenyl)methyl]amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-oxo-2-[(4-phenoxyphenyl)amino]ethoxy]-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-[(1-methylhexyl)amino]-2-oxoethoxy]-benzenepropanoic acid;  
 (2S)-4-[2-[([1,1′-biphenyl]-4-ylmethyl)amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 3-[2-[[cis-4-(1,1-dimethylethyl)cyclohexyl]amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-[4-(3-chlorophenyl)-1-piperazinyl]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-[methyl[(1S)-1-phenylethyl]amino]-2-oxoethoxy]-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-[4-(4-methylphenyl)-1-piperazinyl]-2-oxoethoxy]-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-[[3-(methylphenylamino)propyl]amino]-2-oxoethoxy]-benzenepropanoic acid;  
 (2S)-4-[2-(cyclobutylamino)-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-α-methyl-4-[2-oxo-2-[[2-(4-phenoxyphenyl)ethyl]amino]ethoxy]-α-[4-(trifluoromethoxy)phenoxy]-benzenepropanoic acid;  
 (2S)-4-[2-(heptylamino)-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-[4-(4-fluorophenyl)-1-piperazinyl]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-[[(1S)-1-(1-naphthalenyl)ethyl]amino]-2-oxoethoxy]-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-oxo-2-[[(1R)-1-phenylethyl](phenylmethyl)amino]ethoxy]-benzenepropanoic acid;  
 (2S)-4-[2-[(3,3-diphenylpropyl)amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-[[trans-4-(1,1-dimethylethyl)cyclohexyl]amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-α-methyl-4-[2-oxo-2-[[2-(4-phenoxyphenyl)ethyl]amino]ethoxy]-α-phenoxy-, ethyl ester-benzenepropanoic acid;  
 (2S)-4-[2-[(2,2,3,3,4,4,4-heptafluorobutyl)amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-(3,4-dihydro-2(1H)-isoquinolinyl)-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-3-[2-[[2-(4-ethylphenyl)ethyl]amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-[(1-naphthalenylmethyl)amino]-2-oxoethoxy]-benzenepropanoic acid;  
 (2S)-4-[2-[[(4-chlorophenyl)phenylmethyl]amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-oxo-2-[[2-(2-pyridinyl)ethyl]amino]ethoxy]-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-oxo-2-[[(1S)-1-phenylethyl]amino]ethoxy]-benzenepropanoic acid;  
 (2S)-4-[2-(cyclopentylamino)-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-[4-[bis(4-fluorophenyl)methyl]-1-piperazinyl]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 4-[2-[cyclohexyl[2-(4-ethylphenyl)ethyl]amino]-2-oxoethoxy]-α-ethoxy-benzenepropanoic acid;  
 (2S)-4-[2-[(1,3-benzodioxol-5-ylmethyl)amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 D-Phenylalanine, N-[[4-[(2S)-2-carboxy-2-methoxyethyl]phenoxy]acetyl]-, α-methyl ester;  
 (2S)-4-[2-[4-[(4-fluorophenyl)methyl]-1-piperazinyl]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 α-methoxy-3-[2-oxo-2-[(4-phenoxyphenyl)amino]ethoxy]-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-[(1-methylbutyl)amino]-2-oxoethoxy]-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-[methyl(1-naphthalenylmethyl)amino]-2-oxoethoxy]-benzenepropanoic acid;  
 (2S)-3-[2-[[trans-4-(1,1-dimethylethyl)cyclohexyl]amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-[4-[(4-chlorophenyl)methyl]-1-piperazinyl]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-[4-(4-fluorobenzoyl)-1-piperidinyl]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-[ethyl[(2-fluorophenyl)methyl]amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-[[2-(4-methoxyphenoxy)ethyl]amino]-2-oxoethoxy]-benzenepropanoic acid;  
 (2S)-4-[2-[(1,3-dimethylbutyl)amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-α-(4-fluorophenoxy)-α-methyl-4-[2-oxo-2-[[2-(4-phenoxyphenyl)ethyl]amino]ethoxy]-benzenepropanoic acid;  
 (2S)-4-[2-[(3,3-dimethylbutyl)amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-[4-(4-chlorophenyl)-3-methyl-1-piperazinyl]-2-oxoethoxy]-α-methoxy-benzenepropanioc acid;  
 (2S)-α-methoxy-4-[2-oxo-2-[[(1R)-1-phenylethyl]amino]ethoxy]-benzenepropanoic acid;  
 (2S)-4-[2-[4-(4-acetylphenyl)-1-piperazinyl]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-[(3-ethoxy-3-oxopropyl)(phenylmethyl)amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-[[cis-4-(1,1-dimethylethyl)cyclohexyl]amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-α-ethyl-4-[2-oxo-2-[[2-(4-phenoxyphenyl)ethyl]amino]ethoxy]-α-phenoxy-benzenepropanoic acid;  
 (2S)-4-[2-(hexylamino)-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-oxo-2-[(2-phenylethyl)(phenylmethyl)amino]ethoxy]-benzenepropanoic acid;  
 or  
 (2S)-4-[2-[ethyl[2-(4-methoxyphenyl)-1-methylethyl]amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid.  
 
     
     
         2 . A compound of formula I  
       
         
           
           
               
               
           
         
       
       as well as optical isomers and racemates therof as well as pharmaceutically acceptable salts, prodrugs, solvates and crystalline forms thereof 
 wherein  
 A is situated in the ortho, meta or para position and represents  
                     
 R is hydrogen; 
 —OR a , wherein R a  represents hydrogen, alkyl, aryl or alkylaryl;  
 —NR a R b , wherein R a  and R b  are the same or different and R a  is as defined above and R b  represents hydrogen, alkyl, aryl, alkylaryl, cyano, —OH, —Oalkyl, —Oaryl, —Oalkylaryl, —COR c  or —SO 2 R d , wherein R c  represents hydrogen, alkyl, aryl or alkylaryl and R d  represents alkyl, aryl or alkylaryl;  
 
 R 1  is alkyl, aryl, alkenyl, alkynyl, or when A is  
                     
  R 1  can also be cyano; 
 —OR e , wherein R e  is alkyl, acyl, aryl or alkylaryl;  
 —O—[CH 2 ] m —OR f , wherein R f  represents hydrogen, alkyl, acyl, aryl or alkylaryl and m represents an integer 1-8;  
 —OCONR a R c , wherein R a  and R c  are as defined above;  
 —SR d , wherein R d  is as defined above;  
 —SO 2 NR a R f , wherein R f  and R a  are as defined above;  
 —SO 2 OR a , wherein R a  is as defined above;  
 —COOR d , wherein R d  is as defined above;  
 
 R 2  is hydrogen, halogen, alkyl, aryl, or alkylaryl,  
 R 3  and R 4  are the same or different and each represents hydrogen, alkyl, aryl, or alkylaryl;  
 T represents O, S or a single bond;  
 n represents 1, 2, 3 or 4;  
 R 5  and R 6  are independently selected substituents, comprising C, H, N, O, S, Se, P or halogen atoms, which give compounds of the General Formula I a molecular weight <650;  
 with a first proviso that when A is CH 2 CH(OC 2 H 5 )COOC 2 H 5  or CH 2 CH(OC 2 H 5 )COOH; T is O; n is 1 and R 5  represents a C 2-4 alkyl group then R 6  does not represent a group of formula  
                     
  wherein R x  represents chloro, trifluoromethyl or trifluoromethoxy, R y  represents H or fluoro; and a second proviso that when A is CH 2 CH(OC 2 H 5 )COOC 2 H 5  or CH 2 CH(OC 2 H 5 )COOH; T is O; n is 1 and R 5  represents hexyl or heptyl then R 6  does not represent a group of formula  
                     
  wherein R z  represents phenyl, 2,4-difluorophenyl or cyclohexyl , and n is 1 or 2;  
 provided that the compound of formula I is not:  
 (2S)-4-[2-[[2-[[(2,6-dichlorophenyl)methyl]thio]ethyl]amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-[butyl(1-phenylethyl)amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-oxo-2-[[2-(3-pyridinyl)ethyl]amino]ethoxy]-benzenepropanoic acid;  
 (2S)-α-methyl-4-[2-oxo-2-[[2-(4-phenoxyphenyl)ethyl]amino]ethoxy]-α-phenoxy-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-[(1-methyl-3-phenylpropyl)amino]-2-oxoethoxy]-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-oxo-2-[[2-(4-phenoxyphenyl)ethyl]amino]ethoxy]-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-oxo-2-[4-[4-(trifluoromethyl)phenyl]-1-piperazinyl]ethoxy]-benzenepropanoic acid;  
 (2S)-4-[2-[[2-(4-bromophenyl)ethyl]amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-[[2-[ethyl(3-methylphenyl)amino]ethyl]amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 α-methoxy-α-methyl-4-[2-oxo-2-[[2-(4-phenoxyphenyl)ethyl]amino]ethoxy]-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-[(3-methylbutyl)amino]-2-oxoethoxy]-benzenepropanoic acid;  
 (2S)-4-[2-[4-(diphenylmethyl)-1-piperazinyl]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-(heptylamino)-2-oxoethoxy]-α-methoxy-α-methyl-benzenepropanoic acid;  
 4-[2-[4-(2-fluorophenyl)-1-piperazinyl]-2-oxoethoxy]-α-methoxy-, benzenepropanoic acid;  
 (2S)-4-[2-[4-(4-chlorobenzoyl)-1-piperidinyl]-2-oxoethoxy]-α-methoxy-, benzenepropanoic acid;  
 (2S)-4-[2-[ethyl[(3-methylphenyl)methyl]amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-oxo-2-[(4-phenoxyphenyl)amino]ethoxy]-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-[(1-methylhexyl)amino]-2-oxoethoxy]-benzenepropanoic acid;  
 (2S)-4-[2-[([1,1′-biphenyl]-4-ylmethyl)amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 3-[2-[[cis-4-(1,1-dimethylethyl)cyclohexyl]amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-[4-(3-chlorophenyl)-1-piperazinyl]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-[methyl[(1S)-1-phenylethyl]amino]-2-oxoethoxy]-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-[4-(4-methylphenyl)-1-piperazinyl]-2-oxoethoxy]-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-[[3-(methylphenylamino)propyl]amino]-2-oxoethoxy]-benzenepropanoic acid;  
 (2S)-4-[2-(cyclobutylamino)-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-α-methyl-4-[2-oxo-2-[[2-(4-phenoxyphenyl)ethyl]amino]ethoxy]-α-[4-(trifluoromethoxy)phenoxy]-benzenepropanoic acid;  
 (2S)-4-[2-(heptylamino)-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-[4-(4-fluorophenyl)-1-piperazinyl]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-[[(1S)-1-(1-naphthalenyl)ethyl]amino]-2-oxoethoxy]-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-oxo-2-[[(1R)-1-phenylethyl](phenylmethyl)amino]ethoxy]-benzenepropanoic acid;  
 (2S)-4-[2-[(3,3-diphenylpropyl)amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-[[trans-4-(1,1-dimethylethyl)cyclohexyl]amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-α-methyl-4-[2-oxo-2-[[2-(4-phenoxyphenyl)ethyl]amino]ethoxy]-α-phenoxy-, ethyl ester-benzenepropanoic acid;  
 (2S)-4-[2-[(2,2,3,3,4,4,4-heptafluorobutyl)amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-(3,4-dihydro-2(1H)-isoquinolinyl)-2-oxoethoxy]-α-methoxy-benzenepropanioc acid;  
 (2S)-3-[2-[[2-(4-ethylphenyl)ethyl]amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-[(1-naphthalenylmethyl)amino]-2-oxoethoxy]-benzenepropanoic acid;  
 (2S)-4-[2-[[(4-chlorophenyl)phenylmethyl]amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-oxo-2-[[2-(2-pyridinyl)ethyl]amino]ethoxy]-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-oxo-2-[[(1S)-1-phenylethyl]amino]ethoxy]-benzenepropanoic acid;  
 (2S)-4-[2-(cyclopentylamino)-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-[4-[bis(4-fluorophenyl)methyl]-1-piperazinyl]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 4-[2-[cyclohexyl[2-(4-ethylphenyl)ethyl]amino]-2-oxoethoxy]-α-ethoxy-benzenepropanoic acid;  
 (2S)-4-[2-[(1,3-benzodioxol-5-ylmethyl)amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 D-Phenylalanine, N-[[4-[(2S)-2-carboxy-2-methoxyethyl]phenoxy]acetyl]-, α-methyl ester;  
 (2S)-4-[2-[4-[(4-fluorophenyl)methyl]-1-piperazinyl]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 α-methoxy-3-[2-oxo-2-[(4-phenoxyphenyl)amino]ethoxy]-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-[(1-methylbutyl)amino]-2-oxoethoxy]-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-[methyl(1-naphthalenylmethyl)amino]-2-oxoethoxy]-benzenepropanoic acid;  
 (2S)-3-[2-[[trans-4-(1,1-dimethylethyl)cyclohexyl]amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-[4-[(4-chlorophenyl)methyl]-1-piperazinyl]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-[4-(4-fluorobenzoyl)-1-piperidinyl]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-[ethyl[(2-fluorophenyl)methyl]amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-[[2-(4-methoxyphenoxy)ethyl]amino]-2-oxoethoxy]-benzenepropanoic acid;  
 (2S)-4-[2-[(1,3-dimethylbutyl)amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-α-(4-fluorophenoxy)-α-methyl-4-[2-oxo-2-[[2-(4-phenoxyphenyl)ethyl]amino]ethoxy]-benzenepropanoic acid;  
 (2S)-4-[2-[(3,3-dimethylbutyl)amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-[4-(4-chlorophenyl)-3-methyl-1-piperazinyl]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-oxo-2-[[(1R)-1-phenylethyl]amino]ethoxy]-benzenepropanoic acid;  
 (2S)-4-[2-[4-(4-acetylphenyl)-1-piperazinyl]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-[(3-ethoxy-3-oxopropyl)(phenylmethyl)amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-4-[2-[[cis-4-(1,1-dimethylethyl)cyclohexyl]amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-α-ethyl-4-[2-oxo-2-[[2-(4-phenoxyphenyl)ethyl]amino]ethoxy]-α-phenoxy-benzenepropanoic acid;  
 (2S)-4-[2-(hexylamino)-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 (2S)-α-methoxy-4-[2-oxo-2-[(2-phenylethyl)(phenylmethyl)amino]ethoxy]-benzenepropanoic acid;  
 (2S)-4-[2-[ethyl[2-(4-methoxyphenyl)-1-methylethyl]amino]-2-oxoethoxy]-α-methoxy-benzenepropanoic acid;  
 [[4-[2-oxo-2-[[phenyl[2-(1-piperidinyl)phenyl]methyl]amino]ethyl]phenyl]methyl]-, diethyl ester-propanedioic acid;  
 4-[2-(heptylamino)-2-oxoethyl]-α,α-dimethyl-, ethyl ester-benzenepropanoic acid;  
 2-[[4-(2-amino-2-oxoethoxy)phenyl]methylene]-3-oxo-, methyl ester-butanoic acid;  
 4-[2-[methyl(2-phenylethyl)amino]-2-oxoethyl]-α-phenyl-,ethyl ester-benzenepropanoic acid;  
 4-[2-(heptylamino)-2-oxoethyl]-α,α-dimethyl-, ethyl ester -benzenepropanoic acid;  
 4-[2-[[2-[[(1,1-dimethylethoxy)carbonyl]methylamino]-4-hydroxyphenyl]amino]-2-oxoethoxy]-α-(methylthio)-, ethyl ester-benzenepropanoic acid;  
 [[4-[2-oxo-2-[[phenyl[2-(1-piperidinyl)phenyl]methyl]aminoethyl]phenyl]methyl]-propanedioic acid;  
 N-[3-[4-[2-[methyl(2-phenylethyl)amino]-2-oxoethyl]phenyl]-1-oxo-2-phenylpropyl]-, methyl ester-glycine;  
 4-[2-[methyl(2-phenylethyl)amino]-2-oxoethyl]-α-phenyl-benzenepropanoic acid;  
 N-[3-[4-[2-[methyl(2-phenylethyl)amino]-2-oxoethyl]phenyl]-1-oxo-2-phenylpropyl]-glycine;  
 or  
 4-[3-[methyl(2-phenylethyl)amino]-3-oxopropyl]-α-phenyl-benzenpropanoic acid.  
 
     
     
         3 . A compound according to  claim 1  wherein R 5  and R 6  are independently selected substituents, comprising C, H, N, O, S or halogen atoms, which give compounds of the General Formula I a molecular weight <650.  
     
     
         4 . A compound according to  claim 1  wherein R 5  and R 6  independently represent hydrogen, C 1-13 alkyl, C 2-10 alkenyl or C 2-10 alkynyl each of which is optionally substituted by one or more of the following which may be the same or different: C 3-8 cycloalkyl, C 3-8 cycloalkenyl, aryl, heterocyclyl, heteroaryl, C 1-8 alkoxy (optionally substituted by one or more fluoro), C 3-8 cycloalkoxy, C 3-8 cycloalkenyloxy, aryloxy, heterocyclyloxy, heteroaryloxy, C 3-8 cycloalkyl C 1-8 alkoxy, aryl C 1-8 alkoxy, heterocyclyl C 1-8  alkoxy or heteroaryl C 1-8  alkoxy, fluorine or hydroxy and wherein each of these substituents may optionally be substituted on carbon with one or more substituents which may be the same or different and selected from C 1-8 alkyl, C 3-8 cycloalkyl (optionally substituted by C 1-8 alkyl, C 1-8 alkoxy (optionally substituted by one or more fluoro), halogen, hydroxy, nitro or cyano), aryl (optionally substituted by C 1-8 alkyl, C 1-8 alkoxy (optionally substituted by one or more fluoro), halogen, hydroxy, nitro or cyano), heterocyclyl (optionally substituted by C 1-6 alkyl on any nitrogen), heteroaryl (optionally substituted by C 1-8 alkyl, C 1-8 alkoxy (optionally substituted by one or more fluoro), halogen, hydroxy, nitro or cyano), C 1-8 alkoxy (optionally substituted by one or more fluoro), C 3-8 cycloalkoxy, C 3-8  cycloalkyl C 1-8 alkoxy, aryloxy (optionally substituted by C 1-8 alkyl, C 1-8 alkoxy (optionally substituted by one or more fluoro), halogen, hydroxy, nitro or cyano), aryl C 1-8 alkoxy (wherein the aryl part is optionally substituted by C 1-8 alkyl, C 1-8 alkoxy (optionally substituted by one or more fluoro), halogen, hydroxy, nitro or cyano), halogen, amino, nitro, hydroxy, methylsulfonyl, methylsulfonyloxy, cyano or methylenedioxy, 
 or R 5  and R 6  independently represent C 3 -C 8  cycloalkyl; C 3 -C 8  cycloalkenyl; aryl; heterocyclyl; or heteroaryl; wherein each of these groups is optionally substituted by one or more of the following: C 1-8 alkyl, C 1-8 alkoxy (optionally substituted by one or more fluoro), halogen, hydroxy, nitro or cyano), aryl (optionally substituted by C 1-8 alkyl, C 1-8 alkoxy (optionally substituted by one or more fluoro), halogen, hydroxy, nitro or cyano;    or R 5  and R 6  together with the nitrogen atom to which they are attached form a single or a fused heterocyclic system.    
     
     
         5 . A compound according to  claim 1  wherein A is CH 2 CH(OR t )COOR m  wherein R t  represents C 1-4 alkyl and wherein R m  represents H or C 1-4 alkyl.  
     
     
         6 . A compound according to  claim 1  wherein n represents 2, 3 or 4.  
     
     
         7 . A compound according to  claim 1  wherein R 3  and R 4  are the same or different and each represents alkyl, aryl or alkylaryl.  
     
     
         8 . A compound according to  claim 1  wherein R 3  and R 4  are hydrogen.  
     
     
         9 . A compound according to  claim 1  wherein R 5  and R 6  are independently selected substituents, comprising C, N, O, S, Se, P or halogen atoms.  
     
     
         10 . A compound according to  claim 1  wherein when either of R 5  and R 6  is hydrogen, the other is not an alkyl.  
     
     
         11 . A compound according to  claim 1  wherein R 2  is hydrogen or fluorine.  
     
     
         12 . One or more compounds selected from: 
 (2S)-3-(4-{2-[(2,4-Difluorobenzyl)(octyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-(4-{2-[(2,4-Difluorobenzyl)(nonyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-(4-{2-[(2,4-Difluorobenzyl)(4-ethylbenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-(4-{2-[Benzyl(methyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-2-Ethoxy-3-[4-(2-{heptyl[(1-methylindol-2-yl)methyl]amino}-2-oxoethoxy)phenyl]propanoic acid    (2S)-3-(4-{2-[(2,3-Dimethoxybenzyl)(heptyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-(4-{2-[Butyl(2,3-dimethoxybenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic    (2S)-3-(4-{2-[(4-Chlorobenzyl)(4-isopropylbenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-(4-{2-[(Cyclohexylmethyl)(2,4-difluorobenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-2-Ethoxy-3-(4-{2-[ethyl(2-fluorobenzyl)amino]-2-oxoethoxy}phenyl)propanoic acid    (2S)-3-(4-{2-[[4-(benzyloxy)benzyl](butyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-(4-{2-[bis(4-Chlorobenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-(4-{2-[(4-tert-Butylbenzyl)(4-chlorobenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-[4-(2-{(4-Chlorobenzyl)[4-(trifluoromethyl)benzyl]amino}-2-oxoethoxy)phenyl]-2-ethoxypropanoic acid    (2S)-3-[4-(2-{bis[4-(Trifluoromethyl)benzyl]amino}-2-oxoethoxy)phenyl]-2-ethoxypropanoic acid    (2S)-3-(4-{2-[Benzyl(ethyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid and    (2S)-3-(4-{2-[(4-tert-Butylbenzyl)(ethyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-(4-{2-[benzyl(4-isopropylbenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-2-ethoxy-3-(4-{2-[(3-ethoxypropyl)(4-isopropylbenzyl)amino]-2-oxoethoxy}phenyl)propanoic acid    (2S)-3-(4-{2-[butyl(4-isopropylbenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-(4-{2-[(2-chlorobenzyl)(heptyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-2-ethoxy-3-(4-{2-[heptyl(4-isopropylbenzyl)amino]-2-oxoethoxy}phenyl)propanoic acid    (2S)-3-(4-{2-[[(4-cyanocyclohexyl)methyl](4-isopropylbenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-2-ethoxy-3-(4-{2-[(4-isopropylbenzyl)(2-methoxybenzyl)amino]-2-oxoethoxy}phenyl)propanoic acid    (2S)-3-(4-{2-[(2-chlorobenzyl)(4-chlorobenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-(4-{2-[(4-chlorobenzyl)(2,3-dimethoxybenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-(4-2-[(1,3-benzodioxol-5-ylmethyl)(4-ethoxybenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-(4-{2-[(1,3-benzodioxol-5-ylmethyl)(3-bromobenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-[4-(2-{(1,3-benzodioxol-5-ylmethyl)[3-(trifluoromethyl)benzyl]amino}-2-oxoethoxy)phenyl]-2-ethoxypropanoic acid    (2S)-3-(4-{2-[(3,5-dimethoxybenzyl)(4-ethoxybenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-(4-{2-[(3-chloro-4-fluorobenzyl)(4-ethoxybenzyl)amino]-2-oxoethoxy}phenyl-2-ethoxypropanoic acid    (2S)-2-ethoxy-3-(4-{2-[(4-ethoxybenzyl)(2-thienylmethyl)amino]-2-oxoethoxy}phenyl)propanoic acid    (2S)-3-(4-{2-[benzyl(isopropyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-{4-[2-(dibenzylamino)-2-oxoethoxy]phenyl}-2-ethoxypropanoic acid    (2S)-3-(4-{2-[bis(2-methoxyethyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-2-ethoxy-3-[4-(2-{heptyl[4-(trifluoromethyl)benzyl]amino}-2-oxoethoxy)phenyl]propanoic acid    (2S)-2-ethoxy-3-[4-(2-{heptyl[4-(trifluoromethoxy)benzyl]amino}-2-oxoethoxy)phenyl]propanoic acid    (2S)-2-ethoxy-3-(4-{2-[(4-ethylbenzyl)(heptyl)amino]-2-oxoethoxy}phenyl)propanoic acid    (2S)-3-(4-{2-[(4-tert-butylbenzyl)(heptyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-2-ethoxy-3-(4-{2-[heptyl(4-isobutylbenzyl)amino]-2-oxoethoxy}phenyl)propanoic acid    (2S)-3-(4-{2-[benzyl(heptyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-2-ethoxy-3-(4-{2-[(4-fluorobenzyl)(heptyl)amino]-2-oxoethoxy}phenyl)propanoic acid    (2S)-3-(4-{2-[(4-chlorobenzyl)(heptyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-(4-{2-[(4-bromobenzyl)(heptyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-(4-{2-[butyl(4-ethylbenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-(4-{2-[butyl(4-tert-butylbenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-(4-{2-[butyl(4-isobutylbenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-(4-{2-[benzyl(butyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-(4-{2-[butyl(4-fluorobenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-(4-{2-[(4-bromobenzyl)(butyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-(4-{2-[butyl(2,4-difluorobenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-[4-(2-{(4-chlorobenzyl)[4-(trifluoromethoxy)benzyl]amino}-2-oxoethoxy)phenyl]-2-ethoxypropanoic acid    (2S)-3-(4-{2-[(4-chlorobenzyl)(4-ethylbenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-(4-{2-[(4-chlorobenzyl)(4-isobutylbenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-(4-{2-[benzyl(4-chlorobenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-(4-{2-[(4-chlorobenzyl)(4-fluorobenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-(4-{2-[(4-bromobenzyl)(4-chlorobenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-(4-{2-[(4-chlorobenzyl)(2,4-difluorobenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-2-ethoxy-3-[4-(2-{(4-methylbenzyl)[4-(trifluoromethyl)benzyl]amino}-2-oxoethoxy)phenyl]propanoic acid    (2S)-2-ethoxy-3-[4-(2-{(4-methylbenzyl)[4-(trifluoromethoxy)benzyl]amino}-2-oxoethoxy)phenyl]propanoic acid    (2S)-2-ethoxy-3-(4-{2-[(4-ethylbenzyl)(4-methylbenzyl)amino]-2-oxoethoxy}phenyl)propanoic acid    (2S)-3-(4-{2-[(4-tert-butylbenzyl)(4-methylbenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-2-ethoxy-3-(4-{2-[(4-isobutylbenzyl)(4-methylbenzyl)amino]-2-oxoethoxy}phenyl)propanoic acid    (2S)-3-(4-{2-[benzyl(4-methylbenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-2-ethoxy-3-(4-{2-[(4-fluorobenzyl)(4-methylbenzyl)amino]-2-oxoethoxy}phenyl)propanoic acid    (2S)-3-(4-{2-[(4-chlorobenzyl)(4-methylbenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-(4-{2-[(4-bromobenzyl)(4-methylbenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    (2S)-3-(4-{2-[(2,4-difluorobenzyl)(4-methylbenzyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoic acid    and pharmaceutically acceptable salts thereof    
     
     
         13 . A pharmaceutical formulation comprising a compound according to  claim 1  in admixture with pharmaceutically acceptable adjuvants, diluents and/or carriers.  
     
     
         14 . A method of treating or preventing lipid disorders (dyslipidemia) whether or not associated with insulin resistance comprising the administration of a compound according to  claim 1  to a mammal in need thereof.  
     
     
         15 . The use of a compound according to  claim 1  in the manufacture of a medicament for the treatment of lipid disorders (dyslipidemia) whether or not associated with insulin resistance.  
     
     
         16 . A method of treating or preventing type 2 diabetes comprising the administration of an effective amount of a compound of formula I according to  claim 1  to a mammal in need thereof.  
     
     
         17 . A pharmaceutical composition comprising a compound according to  claim 1  combined with another therapeutic agent that is useful in the treatment of disorders associated with the development and progress of atherosclerosis such as hypertension, hyperlipidaemias, dyslipidaemias, diabetes and obesity.  
     
     
         18 . A compound of formula VI:  
       
         
           
           
               
               
           
         
       
       wherein R5, R6 and n is as defined in any of the preceding claims and X is a leaving group, such as a halide, OSO 2 CH 3 , OTosyl, ONosyl, OSO 2 CF 3 , OC(O)OR, OP(O)(OR) 2  or OSO 2 OR, particularly chloro or bromo.