Glycolipids and analogues thereof as antigens for nk t cells

Abstract

This invention relates to immunogenic compounds which may serve as ligands for NKT (natural killer T) cells and to methods of use thereof in modulating immune responses.

1 . A compound represented by the structure of formula 1: 
     
       
         
         
             
             
         
       
       wherein,
 R═COOR 1 , or CH 2 OR 1 ; 
 R 1 ═H or an alkyl group; 
 R 2 ═H or SO 3   − ; 
 R 3 ═H or OH; 
 R 3 ′═H or OH; 
 R 4 ═H, unsaturated or saturated, alkyl group; 
 R 4 ′═H, unsaturated or saturated, alkyl group; and 
 R 5 ═OH, acetamido or a halogen atom; 
 or a pharmaceutically acceptable salt thereof, 
 wherein if R═CH 2 OR 1 , R 2 ═H, R 3  is OH and R 3 ′ is H, then R 5 =acetamido, halogen atom or OH in an axial position or R 4 ═H, unsaturated or saturated, alkyl chain having 9 carbon atoms or fewer, or R 4 ′═H, unsaturated or saturated, alkyl chain having 20 carbon atoms or fewer. 
 
     
   
   
       2 . The compound of  claim 1 , wherein said compound is represented by the structure of formula 2: 
     
       
         
         
             
             
         
       
       wherein
 R═COOR 1 , or CH 2 OR 1 ; 
 R 1 ═H or an alkyl group; 
 R 2 ═H or SO 3   − ; 
 R 3 ═H or OH; 
 R 3 ′═H or OH; and 
 R 4 ═H, unsaturated or saturated, alkyl group; and 
 R 4 ′═H, unsaturated or saturated, alkyl group; 
 or a pharmaceutically acceptable salt thereof, 
 
       wherein if R═CH 2 OR 1 , R 2 ═H, R 3  is OH and R 3 ′ is H, then R 4 ═H, unsaturated or saturated, alkyl chain having 9 carbon atoms or fewer, or R 4 ′═H, unsaturated or saturated, alkyl chain having 20 carbon atoms or fewer. 
     
   
   
       3 . The compound of  claim 2 , wherein said compound is represented by the structure of formula 3: 
     
       
         
         
             
             
         
       
       wherein,
 R═COOR 1 , or CH 2 OR 1 , 
 R 1 ═H or an alkyl group; 
 R 2 ═SO 3   − ; 
 n=integer; 
 or a pharmaceutically acceptable salt thereof. 
 
     
   
   
       4 . The compound of  claim 3 , wherein said compound is represented by the structure of formula 4: 
     
       
         
         
             
             
         
       
       or a pharmaceutically acceptable salt thereof. 
     
   
   
       5 . The compound of  claim 2 , wherein said compound is represented by the structure of formula 5: 
     
       
         
         
             
             
         
       
     
   
   
       6 . The compound of  claim 2 , wherein said compound is represented by the structure of formula 6: 
     
       
         
         
             
             
         
       
     
   
   
       7 . The compound of  claim 2 , wherein said compound is represented by the structure of formula 7: 
     
       
         
         
             
             
         
       
     
   
   
       8 . The compound of  claim 2 , wherein said compound is represented by the structure of formula 8: 
     
       
         
         
             
             
         
       
     
   
   
       9 . The compound of  claim 1 , wherein said compound is represented by the structure of formula 9: 
     
       
         
         
             
             
         
       
       wherein
 R═COOR 1 , or CH 2 OR 1 ; 
 R 1 ═H or an alkyl group; 
 R 2 ═H or SO 3   − ; 
 R 3 ═OH; 
 R 3 ′═H or OH; and 
 R 4 ═H, unsaturated or saturated, alkyl group; and 
 R 4 ′═H, unsaturated or saturated, alkyl group; 
 or a pharmaceutically acceptable salt thereof, 
 
       wherein if R═CH 2 OR 1 , R 2 ═H and R 3 ′ is H, then R 4 ═H, unsaturated or saturated, alkyl chain having 9 carbon atoms or fewer, or R 4 ′═H, unsaturated or saturated, alkyl chain having 20 carbon atoms or fewer. 
     
   
   
       10 . The compound of  claim 10 , wherein said compound is represented by the structure of formula 10: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof. 
   
   
       11 . A composition, vaccine or adjuvant comprising a compound of  claim 1 . 
   
   
       12 . A compound represented by the structure of formula 11: 
     
       
         
         
             
             
         
       
       wherein,
 R═COOR 1 , or CH 2 OR 1 ; 
 R 1 ═H or an alkyl group; 
 R 2 ═H or SO 3   − ; 
 R 3 ═H or OH; 
 R 4 ═H, unsaturated or saturated, alkyl group; 
 R 5 ═OH, acetamido or a halogen atom; and 
 R 6 ═X-A 
 A= 
 dialkyl phenyl; 
 
     
     
       
         
         
             
             
         
       
       
         X=alkyl, alkenyl, alkoxy, thioalkoxy, substituted furan, or unsubstituted furan; 
         Y═N or C 
         R7=halogen, H, phenyl, alkyl, alkoxy, nitro or CF3; and 
         R8=methyl or H; 
       
       or a pharmaceutically acceptable salt thereof. 
     
   
   
       13 . The compound of  claim 12 , wherein said compound is represented by the structure of formula 12: 
     
       
         
         
             
             
         
       
       or a pharmaceutically acceptable salt thereof. 
     
   
   
       14 . The compound of  claim 13 , wherein said compound is represented by the structure of formula 13: 
     
       
         
         
             
             
         
       
       or a pharmaceutically acceptable salt thereof. 
     
   
   
       15 . The compound of  claim 14 , wherein said compound is represented by the structure of formula 14: 
     
       
         
         
             
             
         
       
       or a pharmaceutically acceptable salt thereof. 
     
   
   
       16 . The compound of  claim 12 , wherein said salt is a sodium salt. 
   
   
       17 . The compound of  claim 12 , wherein said compound is represented by the structure of formula 15: 
     
       
         
         
             
             
         
       
     
   
   
       18 . The compound of  claim 12 , wherein said compound is represented by the structure of formula 16: 
     
       
         
         
             
             
         
       
     
   
   
       19 . The compound of  claim 12 , wherein said compound is a ligand for an NKT (natural killer T) cell, and is in a complex with a CD1 molecule. 
   
   
       20 . A composition, vaccine or adjuvant comprising a compound of  claim 12 .