2 -substituted- 3 -phenylpropionic acid derivatives and their use in the treatment of inflammatory bowel disease

Abstract

The present invention relates to 2-(substituted sulphur, sulphone or sulphoxide)-3-(substituted phenyl) propionic acid derivatives, 2-(substituted oxygen)-3-(substituted phenyl) propionic acid derivatives, benzoic acid derivatives, and derivatives of 2-methyl-2-(phenoxy or phenylthio)propanoic acid and 2-(methylor ethyl)-2-(phenoxy or phenylthio)butanoic acid, to processes for preparing such compounds, to their use in the treatment of inflammatory conditions, and to pharmaceutical compositions containing them.

1 - 29 . (canceled) 
     
     
         30 . A compound of general formula (I′) 
       
         
           
           
               
               
           
         
       
       wherein:
 Y is C, O or S; 
 R 1  represents H, F, CH 3  or CF 3  when Y is C, S, S(O), or SO 2  and C 1 -C 2  alkyl optionally substituted with one or more F when Y is O or S; 
 X represents C, O, S, S(O) or SO 2 ; when Y is C and X is O, S, S(O) or SO 2 ; 
 R 2  represents straight C 1 -C 6  alkyl or branched C 3 -C 4  alkyl, each optionally substituted by one or more F, or R 2  is C 1 -C 3  alkylaryl or C 1 -C 3  alkylheteroaryl, wherein aryl or heteroaryl each optionally is substituted by one or more of the following: halogen, OH, OSO 2 R b , C 1 -C 2  alkoxy, C 1 -C 4  alkyl, which C 1 -C 2  alkoxy or C 1 -C 4  alkyl substituents is each optionally substituted by one or more F; 
 when Y is S and X is C R 2  is methyl optionally substituted by one or more F; 
 R 3  is situated in the ortho, meta or para position and represents F, C 1 -C 4  alkyl or C 1 -C 2  alkoxy, which C 1 -C 4  alkyl or C 1 -C 2  alkoxy substituents is each optionally substituted by one or more F; 
 or R 3  is CH 2 Ph, or NHC(O)OC(CH 3 ) 3 ; 
 p is an integer 0-4; 
 L is situated in the meta or para position and represents (CH 2 ) n C(O)O(CH 2 ) i , (CH 2 ) n C(O)S(CH 2 ) i , (CH 2 ) n OC(O)(CH 2 ) i , or (CH 2 ) n SC(O)(CH 2 ) i , each optionally substituted on any available carbon atom with one or more of the following substituents independently selected from: F, C 2 -C 3  alkenyl, C 1 -C 3  alkyl, C 1 -C 2  alkoxy, which C 1 -C 3  alkyl or C 1 -C 2  alkoxy each optionally is substituted with one or more F; 
 n is an integer 0-3; 
 i is an integer 0-3; 
 A represents aryl or heteroaryl, each optionally substituted by one or more of the following independently selected from: halogen, OH, CN, NR a R a , OR b , SR b , SiR b R b R b , S(O)R b , SO 2 R b , C(O)R b , C(O)NR a R a , NR a C(O)R b , C(O)OR a , OC(O)R b , SO 2 NR a R a , NR a SO 2 R b , NR a C(O)OR b , OC(O)NR a R a , NR a C(O)NR a R a , OSO 2 R b , NO 2 , C 1 -C 4  alkyl which is optionally substituted by one or more F; monocyclic heterocyclyl, monocyclic cycloalkyl, wherein said monocyclic heterocyclyl or monocyclic cycloalkyl are each optionally substituted by one or more of the following independently selected from: F, OH, oxo, CN, NR a R a , OR b , SR b , SiR b R b R b , S(O)R b , SO 2 R b , C(O)R b , C 1 -C 4  alkyl which is optionally substituted by one or more F; monocyclic aryl, monocyclic heteroaryl, wherein said monocyclic aryl or monocyclic heteroaryl are each optionally substituted by one or more of the following independently selected from: halogens, OH, CN, NR a R a , OR b , SR b , SiR b R b R b , S(O)R b , SO 2 R b , OSO 2 R b , NO 2 , C(O)R b , C 1 -C 4 alkyl which is optionally substituted by one or more F, or 
 A is cycloalkyl or heterocyclyl, each optionally substituted by one or more of the following independently selected from: F, OH, oxo, CN, NR a R a , OR b , SR b , SiR b R b R b , S(O)R b , SO 2 R b , C(O)R b , C(O)NR a R a , NR a C(O)R b , C(O)OR a , OC(O)R b , SO 2 NR a R a , NR a SO 2 R b , NR a C(O)OR b , OC(O)NR a R a , NR a C(O)NR a R a , C 1 -C 4  alkyl which is optionally substituted by one or more F; monocyclic heterocyclyl, monocyclic cycloalkyl, wherein said monocyclic heterocyclyl or monocyclic cycloalkyl are each optionally substituted by one or more of the following independently selected from: F, OH, oxo, CN, NR a R a , OR b , SR b , SiR b R b R b , S(O)R b , SO 2 R b , C(O)R b , C 1 -C 4 alkyl which is optionally substituted by one or more F; monocyclic aryl, monocyclic heteroaryl, wherein said monocyclic aryl or monocyclic heteroaryl are each optionally substituted by one or more of the following independently selected from: halogens, OH, CN, NR a R a , OR b , SR b , SiR b R b R b , OS(O)R b , S(O)R b , SO 2 R b , NO 2 , C(O)R b , C 1 -C 4 alkyl which is optionally substituted by one or more F; 
 and in the above definitions 
 C 1 -C 3  alkylaryl binds to X via the alkyl chain; 
 C 1 -C 3  alkylheteroaryl binds to X via the alkyl chain; 
 R a  independently represents H or a straight or branched, saturated or unsaturated C 1 -C 4  alkyl chain optionally substituted by one or more F; and 
 R b  independently represents a straight or branched, saturated or unsaturated C 1 -C 4  alkyl chain optionally substituted by one or more F; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         31 . A compound according to  claim 30  having the general formula (I), 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  represents H, F, CH 3  or CF 3 ; 
 X represents S, S(O) or SO 2 ; 
 R 2  represents straight C 1 -C 6  alkyl or branched C 3 -C 4  alkyl, each optionally substituted by one or more F, or R 2  is C 1 -C 3  alkylaryl or C 1 -C 3  alkylheteroaryl, wherein aryl or heteroaryl each optionally is substituted by one or more of the following: halogen, OH, OSO 2 R b , C 1 -C 2  alkoxy, C 1 -C 4  alkyl, which C 1 -C 2  alkoxy or C 1 -C 4  alkyl substituents is each optionally substituted by one or more F; 
 R 3  is situated in the ortho, meta or para position and represents F, C 1 -C 4  alkyl or C 1 -C 2  alkoxy, which C 1 -C 4  alkyl or C 1 -C 2  alkoxy substituents is each optionally substituted by one or more F; 
 or R 3  is CH 2 Ph, or NHC(O)OC(CH 3 ) 3 ; 
 p is an integer 0-4; 
 L is situated in the meta or para position and represents (CH 2 ) n C(O)O(CH 2 ) i , (CH 2 ) n C(O)S(CH 2 ) i , (CH 2 ) n OC(O)(CH 2 ) i , or (CH 2 ) n SC(O)(CH 2 ) i , each optionally substituted on any available carbon atom with one or more of the following substituents independently selected from: F, C 2 -C 3  alkenyl, C 1 -C 3  alkyl, C 1 -C 2  alkoxy, which C 1 -C 3  alkyl or C 1 -C 2  alkoxy each optionally is substituted with one or more F; 
 n is an integer 0-3; 
 i is an integer 0-3; 
 A represents aryl or heteroaryl, each optionally substituted by one or more of the following independently selected from: halogen, OH, CN, NR a R a , OR b , SR b , SiR b R b R b , S(O)R b , SO 2 R b , C(O)R b , C(O)NR a R a , NR a C(O)R b , C(O)OR a , OC(O)R b , SO 2 NR a R a , NR a SO 2 R b , NR a C(O)OR b , OC(O)NR a R a , NR a C(O)NR a R a , OSO 2 R b , NO 2 , C 1 -C 4 alkyl which is optionally substituted by one or more F; monocyclic heterocyclyl, monocyclic cycloalkyl, wherein said monocyclic heterocyclyl or monocyclic cycloalkyl are each optionally substituted by one or more of the following independently selected from: F, OH, oxo, CN, NR a R a , OR b , SR b , SiR b R b R b , S(O)R b , SO 2 R b , C(O)R b , C 1 -C 4 alkyl which is optionally substituted by one or more F; monocyclic aryl, monocyclic heteroaryl, wherein said monocyclic aryl or monocyclic heteroaryl are each optionally substituted by one or more of the following independently selected from: halogens, OH, CN, NR a R a , OR b , SR b , SiR b R b R b , S(O)R b , SO 2 R b , OSO 2 R b , NO 2 , C(O)R b , C 1 -C 4 alkyl which is optionally substituted by one or more F, or 
 A is cycloalkyl or heterocyclyl, each optionally substituted by one or more of the following independently selected from: F, OH, oxo, CN, NR a R a , OR b , SR b , SiR b R b R b , S(O)R b , SO 2 R b , C(O)R b , C(O)NR a R a , NR a C(O)R b , C(O)OR a , OC(O)R b , SO 2 NR a R a , NR a SO 2 R b , NR a C(O)OR b , OC(O)NR a R a , NR a C(O)NR a R a , C 1 -C 4 alkyl which is optionally substituted by one or more F; monocyclic heterocyclyl, monocyclic cycloalkyl, wherein said monocyclic heterocyclyl or monocyclic cycloalkyl are each optionally substituted by one or more of the following independently selected from: F, OH, oxo, CN, NR a R a , OR b , SR b , SiR b R b R b , S(O)R b , SO 2 R b , C(O)R b , C 1 -C 4  alkyl which is optionally substituted by one or more F; monocyclic aryl, monocyclic heteroaryl, wherein said monocyclic aryl or monocyclic heteroaryl are each optionally substituted by one or more of the following independently selected from: halogens, OH, CN, NR a R a , OR b , SR b , SiR b R b R b , OS(O)R b , S(O)R b , SO 2 R b , NO 2 , C(O)R b , C 1 -C 4 alkyl which is optionally substituted by one or more F; 
 and in the above definitions 
 C 1 -C 3  alkylaryl binds to X via the alkyl chain; 
 C 1 -C 3  alkylheteroaryl binds to X via the alkyl chain; 
 R a  independently represents H or a straight or branched, saturated or unsaturated C 1 -C 4  alkyl chain optionally substituted by one or more F; and 
 R b  independently represents a straight or branched, saturated or unsaturated C 1 -C 4  alkyl chain optionally substituted by one or more F; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         32 . A compound according to  claim 31  wherein:
 R 2  represents C 1 -C 3  alkylaryl or C 1 -C 3  alkylheteroaryl, wherein aryl or heteroaryl each optionally is substituted by one or more of the following: halogen, OH, OSO 2 R b , C 1 -C 2  alkoxy, C 1 -C 4  alkyl, which C 1 -C 2  alkoxy or C 1 -C 4  alkyl substituents is each optionally substituted by one or more F; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         33 . The compound of  claim 30  having the general formula (XI) 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  represents H, F, CH 3  or CF 3 ; 
 X represents O; 
 R 2  represents straight C 1 -C 6  alkyl or branched C 3 -C 4  alkyl, each optionally substituted by one or more F, 
 or R 2  is C 1 -C 3  alkylaryl or C 1 -C 3  alkylheteroaryl, wherein aryl or heteroaryl each optionally is substituted by one or more of the following: halogen, OH, OSO 2 R b , C 1 -C 2  alkoxy, C 1 -C 4  alkyl, which C 1 -C 2  alkoxy or C 1 -C 4  alkyl substituents is each optionally substituted by one or more F; 
 R 3  is situated in the ortho, meta or para position and represents F, C 1 -C 4  alkyl or C 1 -C 2  alkoxy, which C 1 -C 4  alkyl or C 1 -C 2  alkoxy substituents is each optionally substituted by one or more F; 
 or R 3  is CH 2 Ph, or NHC(O)OC(CH 3 ) 3 ; 
 p is an integer 0-4; 
 L is situated in the meta or para position and represents (CH 2 ) n C(O)O(CH 2 ) i , (CH 2 ) n C(O)S(CH 2 ) i , (CH 2 ) n OC(O)(CH 2 ) i  or (CH 2 ) n SC(O)(CH 2 ) i , each optionally substituted on any available carbon atom with one or more of the following substituents independently selected from: F, C 2 -C 3  alkenyl, C 1 -C 3  alkyl, C 1 -C 2  alkoxy, which C 1 -C 3  alkyl or C 1 -C 2  alkoxy each optionally is substituted with one or more F; 
 n is an integer 0-3; 
 i is an integer 0-3; 
 A represents aryl or heteroaryl, each optionally substituted by one or more of the following independently selected from: halogen, OH, CN, NR a R a , OR b , SR b , SiR b R b R b , S(O)R b , SO 2 R b , C(O)R b , C(O)NR a R a , NR a C(O)R b , C(O)OR a , OC(O)R b , SO 2 NR a R a , NR a SO 2 R b , NR a C(O)OR b , OC(O)NR a R a , NR a C(O)NR a R a , OSO 2 R b , NO 2 , C 1 -C 4 alkyl which is optionally substituted by one or more F; monocyclic heterocyclyl, monocyclic cycloalkyl, wherein said monocyclic heterocyclyl or monocyclic cycloalkyl are each optionally substituted by one or more of the following independently selected from: F, OH, oxo, CN, NR a R a , OR b , SR b , SiR b R b R b , S(O)R b , SO 2 R b , C(O)R b , C 1 -C 4  alkyl which is optionally substituted by one or more F; monocyclic aryl, monocyclic heteroaryl, wherein said monocyclic aryl or monocyclic heteroaryl are each optionally substituted by one or more of the following independently selected from: halogens, OH, CN, NR a R a , OR b , SR b , SiR b R b R b , S(O)R b , SO 2 R b , OSO 2 R b , NO 2 , C(O)R b , C 1 -C 4 alkyl which is optionally substituted by one or more F, or 
 A is cycloalkyl or heterocyclyl, each optionally substituted by one or more of the following independently selected from: F, OH, oxo, CN, NR a R a , OR b , SR b , SiR b R b R b , S(O)R b , SO 2 R b , C(O)R b , C(O)NR a R a , NR a C(O)R b , C(O)OR a , OC(O)R b , SO 2 NR a R a , NR a SO 2 R b , NR a C(O)OR b , OC(O)NR a R a , NR a C(O)NR a R a , C 1 -C 4  alkyl which is optionally substituted by one or more F; monocyclic heterocyclyl, monocyclic cycloalkyl, wherein said monocyclic heterocyclyl or monocyclic cycloalkyl are each optionally substituted by one or more of the following independently selected from: F, OH, oxo, CN, NR a R a , OR b , SR b , SiR b R b R b , S(O)R b , SO 2 R b , C(O)R b , C 1 -C 4 alkyl which is optionally substituted by one or more F; monocyclic aryl, monocyclic heteroaryl, wherein said monocyclic aryl or monocyclic heteroaryl are each optionally substituted by one or more of the following independently selected from: halogens, OH, CN, NR a R a , OR b , SR b , SiR b R b R b , S(O)R b , SO 2 R b , OSO 2 R b , NO 2 , C(O)R b , C 1 -C 4 alkyl which is optionally substituted by one or more F; 
 and in the above definitions 
 C 1 -C 3  alkylaryl binds to X via the alkyl chain; 
 C 1 -C 3  alkylheteroaryl binds to X via the alkyl chain; 
 R a  independently represents H or a straight or branched, saturated or unsaturated C 1 -C 4  alkyl chain optionally substituted by one or more F; and 
 R b  independently represents a straight or branched, saturated or unsaturated C 1 -C 4  alkyl chain optionally substituted by one or more F; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         34 . The compound according to  claim 33 , wherein:
 R 2  represents straight C 1 -C 6  alkyl or branched C 3 -C 4  alkyl, each optionally substituted by one or more F;   or a pharmaceutically acceptable salt thereof.   
     
     
         35 . The compound of  claim 30  having the general formula (MI) 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  represents C 1 -C 2  alkyl optionally substituted by one or more F; 
 R 2  represents C 1 -C 2  alkyl optionally substituted by one or more F; 
 X represents O or S; 
 R 3  is situated in the ortho, meta or para position and represents F, C 1 -C 4  alkyl or C 1 -C 2  alkoxy, which C 1 -C 4  alkyl or C 1 -C 2  alkoxy substituents is each optionally substituted by one or more F; 
 or R 3  is CH 2 Ph, or NHC(O)OC(CH 3 ) 3 ; 
 p is an integer 0-4; 
 L is situated in the meta or para position and represents (CH 2 ) n C(O)O(CH 2 ) i , (CH 2 ) n C(O)S(CH 2 ) i , (CH 2 ) n OC(O)(CH 2 ) i , or (CH 2 ) n SC(O)(CH 2 ) i , each optionally substituted on any available carbon atom with one or more of the following substituents independently selected from: F, C 2 -C 3  alkenyl, C 1 -C 3  alkyl, C 1 -C 2  alkoxy, which C 1 -C 3 -alkyl or C 1 -C 2  alkoxy each optionally is substituted with one or more F; 
 n is an integer 0-3; 
 i is an integer 0-3; 
 A represents aryl or heteroaryl, each optionally substituted by one or more of the following independently selected from: halogen, OH, CN, NR a R a , OR b , SR b , SiR b R b R b , S(O)R b , SO 2 R b , C(O)R b , C(O)NR a R a , NR a C(O)R b , C(O)OR a , OC(O)R b , SO 2 NR a R a , NR a SO 2 R b , NR a C(O)OR b , OC(O)NR a R a , NR a C(O)NR a R a , OSO 2 R b , NO 2 , C 1 -C 4  alkyl which is optionally substituted by one or more F; monocyclic heterocyclyl, monocyclic cycloalkyl, wherein said monocyclic heterocyclyl or monocyclic cycloalkyl are each optionally substituted by one or more of the following independently selected from: F, OH, oxo, CN, NR a R a , OR b , SR b , SiR b R b R b , S(O)R b , SO 2 R b , C(O)R b , C 1 -C 4  alkyl (which is optionally substituted by one or more F); monocyclic aryl, monocyclic heteroaryl, wherein said monocyclic aryl or monocyclic heteroaryl are each optionally substituted by one or more of the following independently selected from: halogens, OH, CN, NR a R a , OR b , SR b , SiR b R b R b , S(O)R b , SO 2 R b , OSO 2 R b , NO 2 , C(O)R b , C 1 -C 4  alkyl which is optionally substituted by one or more F, or 
 A is cycloalkyl or heterocyclyl, each optionally substituted by one or more of the following independently selected from: F, OH, oxo, CN, NR a R a , OR b , SR b , SiR b R b R b , S(O)R b , SO 2 R b , C(O)R b , C(O)NR a R a , NR a C(O)R b , C(O)OR a , OC(O)R b , SO 2 NR a R a , NR a SO 2 R b , NR a C(O)OR b , OC(O)NR a R a , NR a C(O)NR a R a , C 1 -C 4 alkyl which is optionally substituted by one or more F; monocyclic heterocyclyl, monocyclic cycloalkyl, wherein said monocyclic heterocyclyl or monocyclic cycloalkyl are each optionally substituted by one or more of the following independently selected from: F, OH, oxo, CN, NR a R a , OR b , SR b , SiR b R b R b , S(O)R b , SO 2 R b , C(O)R b , C 1 -C 4 alkyl which is optionally substituted by one or more F; monocyclic aryl, monocyclic heteroaryl, wherein said monocyclic aryl or monocyclic heteroaryl are each optionally substituted by one or more of the following independently selected from: halogens, OH, CN, NR a R a , OR b , SR b , SiR b R b R b , S(O)R b , SO 2 R b , OSO 2 R b , NO 2 , C(O)R b , C 1 -C 4  alkyl which is optionally substituted by one or more F; 
 and in the above definitions 
 R a  independently represents H or a straight or branched, saturated or unsaturated C 1 -C 4  alkyl chain optionally substituted by one or more F; and 
 R b  independently represents a straight or branched, saturated or unsaturated C 1 -C 4  alkyl chain optionally substituted by one or more F; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         36 . The compound according to  claim 35 , wherein
 R 1  represents C 1  alkyl optionally substituted by one or more F;   R 2  represents C 1 =alkyl optionally substituted by one or more F;   X represents O;   or a pharmaceutically acceptable salt thereof.   
     
     
         37 . A compound having the general formula (CI) 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  represents F; 
 w is an integer 0-4; 
 M is situated in the ortho or meta position and represents COOH; 
 Q represents C 1 -C 2  alkylX or XC 1 -C 2  alkyl; 
 X represents S or O; 
 R 2  is situated in the ortho, meta or para position and represents F; 
 p is an integer 0-4; 
 L is situated in the meta or para position and represents (CH 2 ) n C(O)O(CH 2 ) i , (CH 2 ) n C(O)S(CH 2 ) i , (CH 2 ) n OC(O)(CH 2 ) i , or (CH 2 ) n SC(O)(CH 2 ) i , each optionally substituted on any available carbon atom with one or more of the following substituents independently selected from: F, C 2 -C 3 alkenyl, C(O)OC 1 -C 3  alkyl, heteroaryl, C 1 -C 3  alkyl, C 1 -C 2  alkoxy, which C 1 -C 3  alkyl or C 1 -C 2 =alkoxy substituents is each optionally substituted with one or more F; 
 n is an integer 0-3; 
 i is an integer 0-3; 
 A represents aryl or heteroaryl, each optionally substituted by one or more of the following independently selected from: halogen, OH, CN, NR a R a , OR b , SR b , SiR b R b R b , S(O)R b , SO 2 R b , C(O)R b , C(O)NR a R a , NR a C(O)R b , C(O)OR a , OC(O)R b , SO 2 NR a R a , NR a SO 2 R b , NR a C(O)OR b , OC(O)NR a R a , NR a C(O)NR a R a , OSO 2 R b , NO 2 , C 1 -C 4  alkyl (which is optionally substituted by one or more F); monocyclic heterocyclyl, monocyclic cycloalkyl, wherein said monocyclic heterocyclyl or monocyclic cycloalkyl are each optionally substituted by one or more of the following independently selected from: F, OH, oxo, CN, NR a R a , OR b , SR b , SiR b R b R b , S(O)R b , SO 2 R b C(O)R b , C 1 -C 4  alkyl which is optionally substituted by one or more F; monocyclic aryl, monocyclic heteroaryl, wherein said monocyclic aryl or monocyclic heteroaryl are each optionally substituted by one or more of the following independently selected from: halogen, OH, CN, NR a R a , OR b , SR b , SiR b R b R b , S(O)R b , SO 2 R b , OSO 2 R b , NO 2 , C(O)R b , C 1 -C 4  alkyl which is optionally substituted by one or more F, or 
 A is cycloalkyl or heterocyclyl, each optionally substituted by one or more of the following independently selected from: F, OH, oxo, CN, NR a R a , OR b , SR b , SiR b R b R b , S(O)R b , SO 2 R b , C(O)R b , C(O)NR a R a , NR a C(O)R b , C(O)OR a , OC(O)R b , SO 2 NR a R a , NR a SO 2 R b , NR a C(O)OR b , OC(O)NR a R a , NR a C(O)NR a R a , C 1 -C 4  alkyl which is optionally substituted by one or more F; monocyclic heterocyclyl, monocyclic cycloalkyl, wherein said monocyclic heterocyclyl or monocyclic cycloalkyl are each optionally substituted by one or more of the following independently selected from: F, OH, oxo, CN, NR a R a , OR b , SR b , SiR b R b R b , S(O)R b , SO 2 R b , C(O)R b , C 1 -C 4  alkyl which is optionally substituted by one or more F; monocyclic aryl, monocyclic heteroaryl, wherein said monocyclic aryl or monocyclic heteroaryl are each optionally substituted by one or more of the following independently selected from: halogen, OH, CN, NR a R a , OR b , SR b , SiR b R b R b , S(O)R b , SO 2 R b , OSO 2 R b , NO 2 , C(O)R b , C 1 -C 4  alkyl which is optionally substituted by one or more F; 
 and in the above definitions 
 R a  independently represents H or a straight or branched, saturated or unsaturated C 1 -C 4  alkyl chain optionally substituted by one or more F; and 
 R b  independently represents a straight or branched, saturated or unsaturated C 1 -C 4  alkyl chain optionally substituted by one or more F; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         38 . The compound according to  claim 37 , wherein:
 Q represents XC 1 -C 2  alkyl;   X represents S or O;   L is situated in the meta or para position and represents (CH 2 ) n C(O)O(CH 2 ) i  or (CH 2 ) n OC(O)(CH 2 ) i , each optionally substituted on any available carbon atom with one or more of the following substituents independently selected from: F, C 2 -C 3  alkenyl, C(O)OC 1 -C 3  alkyl, heteroaryl, C 1 -C 3  alkyl, C 1 -C 2  alkoxy, which C 1 -C 3  alkyl or C 1 -C 2  alkoxy substituents is each optionally substituted with one or more F;   or a pharmaceutically acceptable salt thereof.   
     
     
         39 . A compound according to  claim 30  or  35  selected from one or more of the following:
 4-Methanesulfonyloxy-benzoic acid 4-{2-carboxy-2-[2-(4-fluoro-phenyl)-ethylsulfanyl]-ethyl}-benzyl ester; 
 2-[2-(4-Fluoro-phenyl)-ethylsulfanyl]-3-{4-[2-(4-methanesulfonyloxy-phenyl)-acetoxymethyl]-phenyl}-propionic acid; 
 2-[2-(4-Fluoro-phenyl)-ethylsulfanyl]-3-[4-(4-trifluoromethyl-benzyloxycarbonylmethyl)-phenyl]-propionic acid; 
 2-[2-(4-Fluoro-phenyl)-ethylsulfanyl]-3-[4-(4-methanesulfonyloxy-benzyloxycarbonylmethyl)-phenyl]-propionic acid; 
 2-[2-(4-Fluoro-phenyl)-ethylsulfanyl]-3-(4-{2-[2-(4-methanesulfonyloxy-phenyl)-acetoxy]-ethyl}-phenyl)-propionic acid; 
 2-[2-(4-Fluoro-phenyl)-ethylsulfanyl]-3-(4-{3-[2-(4-methanesulfonyloxy-phenyl)-acetoxy]-propyl}-phenyl)-propionic acid; 
 2-[2-(4-Fluoro-phenyl)-ethylsulfanyl]-3-[4-(2-phenyl-propionyloxymethyl)-phenyl]-propionic acid; 
 2-[2-(4-Fluoro-phenyl)-ethylsulfanyl]-3-{-4-[2-(4-methoxylphenylacetoxymethyl]phenyl}-propionic acid; 
 2-[2-(4-Fluoro-phenyl)-ethylsulfanyl]-3-{4-[2-(4-isobutyl-phenyl)-propionyloxymethyl]-phenyl}-propionic acid; 
 2-[2-(4-Fluoro-phenyl)-ethylsulfanyl]-3-[4-(2-pyridin-2-yl-acetoxymethyl)-phenyl]-propionic acid; 
 2-[2-(4-Fluoro-phenyl)-ethylsulfanyl]-3-{4-[2-(4-methyl-piperazin-1-yl)-acetoxymethyl]-phenyl}-propionic acid; 
 4-{2-Carboxy-2-[2-(4-fluoro-phenyl)-ethylsulfanyl]-ethyl}-benzoic acid 2-phenyl-5 trifluoromethyl-oxazol-4-ylmethyl ester; 
 2-Phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid 4-{2-carboxy-2-[2-(4-fluoro-phenyl)-ethylsulfanyl]-ethyl}-benzyl ester; 
 4-{2-Carboxy-2-[2-(4-fluoro-phenyl)-ethylsulfanyl]-ethyl}-benzoic acid 2-(5-methyl-2 phenyl-oxazol-4-yl)-ethyl ester; 
 2-[2-(4-Fluoro-phenyl)-ethylsulfanyl]-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)acetoxymethyl]-phenyl}-propionic acid; 
 4-{2-Carboxy-2-[2-(4-fluoro-phenyl)-ethylsulfanyl]-ethyl}-benzoic acid 4-methanesulfonyloxy-benzyl ester; 
 2-[2-(4-Fluoro-phenyl)-ethanesulfonyl]-3-[4-(4-trifluoromethyl-benzyloxycarbonylmethyl)-phenyl]-propionic acid; 
 2-[2-(4-Fluoro-phenyl)-ethylsulfanyl]-3-{4-[2-(4-methanesulfonyloxy-phenyl)-ethylsulfanylcarbonyl]-phenyl}-propionic acid; 
 (−)-2-[2-(4-Fluoro-phenyl)-ethylsulfanyl]-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-acetoxymethyl]-phenyl}-propionic acid; 
 4-{(−)-2-Carboxy-2-[2-(4-fluoro-phenyl)-ethylsulfanyl]-ethyl}-benzoic acid 2-(5-methyl-2-phenyl-oxazol-4-yl)-ethyl ester; 
 (S)-2-Ethoxy-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-acetoxy]-phenyl}-propionic acid; 
 (S)-3-{4-[2-(4-tert-Butoxycarbonylamino-phenyl)-acetoxy]-phenyl}-2-ethoxy-propionic acid; 
 3-{3-Benzyl-4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-acetoxy]-phenyl}-2-ethoxy-propionic acid; 
 3-{3-Benzyl-4-[2-(4-tert-butoxycarbonylamino-phenyl)-acetoxy]-phenyl}-2-ethoxy-propionic acid; 
 2-Ethoxy-3-{3-methyl-4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-acetoxy]-phenyl}-propionic acid; 
 3-{4-[2-(4-tert-Butoxycarbonylamino-phenyl)-acetoxy]-3-methyl-phenyl}-2-ethoxy-propionic acid; 
 4-(2-Carboxy-2-ethoxy-ethyl)-benzoic acid 4-methanesulfonyloxy-benzyl ester; 
 2-[3-(4-Trifluoromethyl-benzyloxycarbonylmethyl)-phenylsulfanylmethyl]-benzoic acid; 
 2-{4-[2-(4-Trifluoromethyl-phenyl)-acetoxymethyl]-phenylsulfanylmethyl}-benzoic acid; 
 2-[4-(4-Trifluoromethyl-benzyloxycarbonylmethyl)-phenylsulfanylmethyl]-benzoic acid; 
 2-{3-[1-(4-Trifluoromethyl-phenyl)-ethoxycarbonylmethyl]phenylsulfanylmethyl}-benzoic acid; 
 2-{3-[2-(4-Trifluoromethyl-phenyl)-ethoxycarbonylmethyl]-phenylsulfanylmethyl}-benzoic acid; 
 2-[4-(2,6-Dimethyl-benzyloxycarbonylmethyl)-phenylsulfanylmethyl]-benzoic acid; 
 2-[4-(1-Phenyl-but-3-enyloxycarbonylmethyl)-phenylsulfanylmethyl]-benzoic acid; 
 2-[3-(1-Methoxycarbonyl-2-phenyl-ethoxycarbonylmethyl)-phenylsulfanylmethyl]-benzoic acid; 
 2-{4-[2-(3,4-Dimethoxy-phenyl)-ethoxycarbonylmethyl]-phenylsulfanylmethyl}-benzoic acid; 
 2-[4-(1-Methoxycarbonyl-2-phenylethoxycarbonylmethyl)phenylsulfanylmethyl]-benzoic acid; 
 2-{3-[2-(2-Trifluoromethylphenyl)ethoxycarbonylmethyl]phenylsulfanylmethyl}-benzoic acid; 
 2-[4-(Oxazol-2-yl-phenyl-methoxycarbonylmethyl)-phenylsulfanylmethyl]-benzoic acid; 
 2-{4-[2-(2-Trifluoromethylphenyl)ethoxycarbonylmethyl]phenylsulfanylmethyl}-benzoic acid; 
 2-[3-(2,6-Dimethyl-benzyloxycarbonylmethyl)-phenylsulfanylmethyl]-benzoic acid; 
 2-[3-(4-Pyrazol-1-yl-benzyloxycarbonylmethyl)-phenylsulfanylmethyl]-benzoic acid; 
 2-[4-(4-Pyrazol-1-yl-benzyloxycarbonylmethyl)-phenylsulfanylmethyl]-benzoic acid; or 
 2-{3-[2-(3,4-Dimethoxy-phenyl)-ethoxycarbonylmethyl]-phenylsulfanylmethyl}-benzoic acid; and 
 4-(1-Carboxy-1-methyl-ethoxy)-benzoic acid 4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethyl ester; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         40 . A process for preparing a compound according to any of  claim 33  or  34 , wherein
 R 1  is hydrogen, X is oxygen, R 2 , R 3 , p, L, n, i, and A are as defined in  claim 35 , comprising deprotecting a compound of formula V, 
 
       
         
           
           
               
               
           
         
         wherein X is oxygen, Y is oxygen when W is H, H, or Y is H, H when W is oxygen, and PG 2  is a protecting group, such as benzyl, using a hydrogenating reagent, such as hydrogen (H 2 ) in the presence of palladium on carbon (Pd—C). 
       
     
     
         41 . A compound according to any of  claim 30 ,  31 ,  33 ,  35 , or  37 , or a pharmaceutically acceptable salt thereof, for use as a medicament. 
     
     
         42 . The use of a compound according to any of  claim 30 ,  31 ,  33 ,  35 , or  37 , or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment and/or prophylaxis of Crohn's disease, ulcerative colitis, proctitis, gastric inflammation, celiac disease, appendicitis, microscopic colitis, distal proctitis, or indeterminant colitis. 
     
     
         43 . A method of treatment for Crohn's disease, ulcerative colitis, proctitis, gastric inflammation, celiac disease, appendicitis, microscopic colitis, distal proctitis, or indeterminant colitis comprising the administration of a therapeutically effective amount of a compound according to any of  claim 30 ,  31 ,  33 ,  35 , or  37 , or a pharmaceutically acceptable salt thereof, to a mammal in need thereof. 
     
     
         44 . A pharmaceutical formulation comprising a compound according to any of  claim 30 ,  31 ,  33 ,  35 , or  37 , or a pharmaceutically acceptable salt thereof, in admixture with a pharmaceutically acceptable adjuvant, diluent and/or carrier.