Compositions for the Treatment or Prophylaxis of Viral Infections

Abstract

A compound of the general formula (III): wherein X is O, S, NH or CH 2 ; Y is O, S or NH; Z is O, S or CH 2 ; R 1 is C 1-8 alkyl, especially C 1-6 alkyl, preferably n-alkyl, e.g., n-pentyl or n-hexyl; at least one of R 2 and R 3 is H—[R 4 -R 5 ] n —R 6 —, in which: H—[R 4 -R 5 ] n — comprises an oligopeptide, R 4 being an amino acid and R 5 being an amino acid selected from proline, alanine, hydroxyproline, dihydroxyproline, thiazolidinecarboxylic acid (thioproline), dehydroproline, pipecolic acid (L-homoproline), azetidinecarboxylic acid, aziridinecarboxylic acid, glycine, serine, valine, leucine, isoleucine and threonine, R 6 is a neutral, non-polar amino acid moiety that is bonded to R 5 by a peptide bond, and n is 1, 2, 3, 4 or 5; and the other of R 3 and R 2 is H—[R 4 -R 5 ] n —R 6 — or H; or a pharmaceutically acceptable salt thereof.

What is claimed is: 
     
         1 . A compound of the general formula (III): 
       
         
           
           
               
               
           
         
       
       wherein X is O, S, NH or CH 2 ;
 Y is O, S or NH; 
 Z is O, S or CH 2 ; 
 R 1  is C 1-8  alkyl; 
 at least one of R 2  and R 3  is H—[R 4 -R 5 ] n —R 6 —, in which: 
 H—[R 4 -R 5 ] n — comprises an oligopeptide, R 4  being an amino acid and R 5  being an amino acid selected from proline, alanine, hydroxyproline, dihydroxyproline, thiazolidinecarboxylic acid (thioproline), dehydroproline, pipecolic acid (L-homoproline), azetidinecarboxylic acid, aziridinecarboxylic acid, glycine, serine, valine, leucine, isoleucine and threonine; 
 R 6  is a neutral, non-polar amino acid moiety that is bonded to R 5  by a peptide bond, and 
 n is 1, 2, 3, 4 or 5; and 
 
       the other of R 3  and R 2  is H—[R 4 -R 5 ] n —R 6 — or H; or 
       a pharmaceutically acceptable salt thereof. 
     
     
         2 . A compound as claimed in  claim 1  having a structural formula selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         3 . A method of synthesizing the compound of the invention, said method comprising conjugating a compound of formula (II): 
       
         
           
           
               
               
           
         
         wherein X is O, S, NH or CH 2 ; 
         Y is O, S or NH; 
         Z is O, S or CH 2 ; 
         R 1  is C 1-6  alkyl; 
         at least one of R 13  and R 14  is a neutral, non-polar amino acid moiety having a free amino terminus; and 
         the other of R 14  and R 13  is H, the resulting hydroxyl group be optionally protected, or a neutral, non-polar amino acid moiety; 
         with a protected oligopeptide of formula Z′—[R 4 -R 5 ] n —OH to form a peptide bond between R 5  and at least one of R 13  or R 14 , wherein R 4  and R 5  are defined above and Z′ is an amino-protecting group to protect the free amino terminus, and thereafter removing said protecting group. 
       
     
     
         4 . A pharmaceutical composition comprising a compound as claimed in  claim 1  in combination with a pharmaceutically acceptable excipient.