Thiocarboxamide derivatives

Abstract

Compounds of formula (1): wherein: R 1 is a hydrogen atom or an optionally substituted cycloaliphatic, polycycloaliphatic, heterocycloaliphatic; polyheterocycloaliphatic, aromatic, or heteroaromatic group; Alk 1 is an optionally substituted aliphatic or heteroaliphatic chain; L 1 is a linker atom or group; r and s is each zero or an integer 1; R 2 and R 3 , which may be the same or different, is each a hydrogen or halogen atom or a straight or branched alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyl or nitro group; Alk 2 is a straight or branched alkylene chain; is zero or an integer 1; R 4 is a hydrogen atom or a methyl group; R 5 is a hydrogen atom or a straight or branched alkyl group; R 6 is a group —(CH 2 ) t R 7 in which t is zero or the integer 1 and R 7 is an optionally substituted polycycloaliphatic, heterocycloaliphatic, polyheterocycloaliphatic, aromatic or heteroaromatic group; R is a carboxylic acid (—CO 2 H) or a derivative thereof; and the salts, solvates and hydrates thereof are described The compounds are able to inhibit the binding of alpha 4 integrins to their ligands and are of use in the prophylaxis and treatment of immune or inflammatory disorders.

1 . A compound of formula (1):  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1  is a hydrogen atom or an optionally substituted cycloaliphatic, polycycloaliphatic, heterocycloaliphatic, polyheterocycloaliphatic, aromatic or heteroaromatic group;  
 Alk 1  is an optionally substituted aliphatic or heteroaliphatic chain;  
 L 1  is a linker atom or group;  
 r and s is each zero or an integer 1;  
 R 2  and R 3 , which may be the same or different, is each a hydrogen or halogen atom or a straight or branched alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyl or nitro group;  
 Alk 2  is a straight or branched alkylene chain;  
 m; is zero or an integer 1;  
 R 4  is a hydrogen atom or a methyl group;  
 R 5  is a hydrogen atom or a straight or branched alkyl group;  
 R 6  is a group —(CH 2 ) t R 7  in which t is zero or the integer 1 and R 7  is an optionally substituted polycycloaliphatic, heterocycloaliphatic, polyhetero-cycloaliphatic, aromatic or heteroaromatic group;  
 R is a carboxylic acid (—CO 2 H) or a derivative thereof;  
 and the salts, solvates and hydrates thereof.  
 
     
     
         2 . A compound according to  claim 1  wherein R is a —CO 2 H group.  
     
     
         3 . A compound according to  claim 1  wherein Alk is a —CH 2 — chain and m is an integer 1.  
     
     
         4 . A compound according to  claim 1  wherein R 4  and R 5  is each a hydrogen atom.  
     
     
         5 . A compound according to  claim 1  wherein -Alk 1 L 1 - is a —CH 2 O— or —CON(R 8 )— group where R 8  is a hydrogen atom or a straight or branched alkyl group.  
     
     
         6 . A compound according to  claim 1  wherein R 1  is an optionally substituted aromatic or heteroaromatic group.  
     
     
         7 . A compound according to  claim 6  wherein R 1  is an optionally substituted phenyl, pyridyl or pyrimidinyl group.  
     
     
         8 . A compound according to  claim 1  wherein R 6  is an optionally substituted heterocycloaliphatic, romatic or heteroaromatic group.  
     
     
         9 . A compound according to claims  8  wherein R 6  is an optionally substituted pyrrolidinyl, thiazolidinyl, phenyl or pyridyl group.  
     
     
         10 . A pharmaceutical composition comprising a compound of formula (1):  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1  is a hydrogen atom or an optionally substituted cycloaliphatic, polycycloaliphatic, heterocycloaliphatic, polyheterocycloaliphatic, aromatic or heteroaromatic group;  
 Alk 1  is an optionally substituted aliphatic or heteroaliphatic chain;  
 L 1  is a linker atom or group,  
 r and s is each zero or an integer 1;  
 R 2  and R 3 , which may be the same or different, is each a hydrogen or halogen atom or a straight or branched alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyl or nitro group;  
 Alk 2  is a straight or branched alkylene chain;  
 m is zero or an integer 1;  
 R 4  is a hydrogen atom or a methyl group;  
 R 5  is a hydrogen atom or a straight or branched alkyl group;  
 R 6  is a group —(CH 2 ) t R 7  in which t is zero or the integer 1 and R 7  is an optionally substituted polycycloaliphatic, heterocycloaliphatic, polyhetero-cycloaliphatic, aromatic or heteroaromatic group;  
 R is a carboxylic acid (—CO 2 H) or a derivative thereof;  
 and the salts, solvates and hydrates thereof; together with one or more pharmaceutically acceptable carriers, excipients or diluents.