Glycolipids and analogues thereof as antigens for nkt cells

Abstract

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

1 - 40 . (canceled) 
     
     
         41 . A method for stimulating an immune response in a subject in need of said stimulating of the immune response, the method comprising: (a) administering to the subject a therapeutically effective amount of a compound, composition, or vaccine designed to stimulate an immune response, wherein the compound, composition, or vaccine, comprises an adjuvant, wherein the adjuvant comprises 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  and R 4 ′ are independently chosen from
 (a) H, 
 (b) alkyl; 
 (c) alkenyl; and 
 (d) oxaalkyl; 
 
 R 5 =OH, acetamido or a halogen atom; 
 
       
       or a pharmaceutically acceptable salt thereof,
 wherein if R=CH 2 OR 1  where R 1  is H, then R 2 =SO 3   − , and 
 wherein if R=CH 2 OR 1 , R 2 =H, R 3  is OH and R 3 ′ is H, then
 R 5 =acetamido or a halogen atom; 
 
 or 
 a compound represented by the structure of formula (17): 
 
       
         
           
           
               
               
           
         
         wherein 
         R 4  is selected from: 
         (a) alkyl, 
         (b) alkenyl, 
         (c) alkyl terminating in aryl, substituted aryl, heteroaryl or substituted heteroaryl; and 
         (d) alkenyl terminating in aryl, substituted aryl, heteroaryl or substituted heteroaryl, and 
         R 6  is 
       
       
         
           
           
               
               
           
         
         X is an alkyl chain; and 
       
       R 7  is chosen from halogen, H, phenyl, alkyl, alkoxy, nitro, and CF 3 . 
     
     
         42 . The method according to  claim 41 , wherein R 4  and X of the structure of formula (17) are saturated alkyl groups containing from 1 to 30 carbons. 
     
     
         43 . The method according to  claim 42 , wherein R 4  and X of the structure of formula (17) are saturated alkyl groups containing from 5 to 25 carbons. 
     
     
         44 . The method according to  claim 43 , wherein R 7  of the structure of formula (17) is H. 
     
     
         45 . The method according to  claim 44 , wherein the compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         46 . The method according to  claim 43 , wherein R 7  of the structure of formula (17) is halogen. 
     
     
         47 . The method according to  claim 41 , wherein the compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         48 . The method according to  claim 43 , wherein R 7  of the structure of formula (17) is alkoxy. 
     
     
         49 . The method according to  claim 48 , wherein the compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         50 . The method according to  claim 43 , wherein R 7  of the structure of formula (17) is CF 3 . 
     
     
         51 . The method according to  claim 50 , wherein the compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         52 . The method according to  claim 43 , wherein R 7  of the structure of formula (17) is phenyl. 
     
     
         53 . The method according to  claim 52 , wherein the compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         54 . The method according to  claim 41 , wherein the structure of formula (17):
 R 4  is   
       
         
           
           
               
               
           
         
         X is an alkyl chain; and 
         R 7  is chosen from halogen, H, phenyl, alkyl, alkoxy, nitro, and CF 3 . 
       
     
     
         55 . The method according to  claim 54 , wherein R 6  and X are saturated alkyl groups containing from 1 to 30 carbons. 
     
     
         56 . The method according to  claim 55 , wherein R 6  and X are substituted alkyl groups containing from 2 to 10 carbons. 
     
     
         57 . The method according to  claim 56 , wherein R 7  is H. 
     
     
         58 . The method according to  claim 57 , wherein the compound is selected from the group consisting of: