Oligosaccharide Compounds

Abstract

The invention relates generally to oligosaccharide compounds and the use of these compounds as pharmaceuticals for treating diseases or conditions in which it is desirable to inhibit β-secretase.

1 . An octasaccharide, decasaccharide or dodecasaccharide compound of the formula (I):
   H-Q-V-W-X-Y-Z-A   (I)
   where:   A is an optionally substituted alkoxy, aralkoxy, aryloxy group;   W, X, Y and Z are each independently a disaccharide of formula (i);   V is a disaccharide of formula (i) or V is absent; and   Q is a disaccharide of formula (i) or Q is absent   
       
         
           
           
               
               
           
         
         where: 
         R 1  is SO 3 H; 
         R 2  is H; 
         R 3  is acyl; 
         R 4  is H or SO 3 H; and 
         each R 5  and R 6  is independently selected from COOH and H; provided that one of R 5  and R 6  in each disaccharide is H and the other is COOH; 
         and provided that all R 3  groups in the octasaccharide, decasaccharide or dodecasaccharide are the same as each other and provided that all R 4  groups in the octasaccharide, decasaccharide or dodecasaccharide are the same as each other; or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . A compound as claimed in  claim 1  where R 5  is H and R 6  is COOH or a salt form of COOH. 
     
     
         3 . A compound as claimed in  claim 1  where R 5  is COOH or a salt form of COOH and R 6  is H. 
     
     
         4 . A compound as claimed in  claim 1  which contains at least one disaccharide of formula (i) where R 5  is H and R 6  is COOH or a salt form of COOH and at least one disaccharide of formula (i) where R 5  is COOH or a salt form of COOH and R 6  is H. 
     
     
         5 . A compound as claimed in any one of  claims 1  to  4  where the pharmaceutically acceptable salt is an ammonium salt, a metal salt, a salt of an organic cation, or a mixture thereof. 
     
     
         6 . A compound as claimed in any one of  claims 1  to  5  where Q and V are absent and the compound of formula (I) is an octasaccharide. 
     
     
         7 . A compound as claimed in any one of  claims 1  to  5  where one of Q and V is a disaccharide of formula (i) and the other is absent and the compound of formula (I) is a decasaccharide. 
     
     
         8 . A compound as claimed in any one of  claims 1  to  5  where Q and V are each independently a disaccharide of formula (i) and the compound of formula (I) is a dodecasaccharide. 
     
     
         9 . A compound as claimed in any one of  claims 1  to  8  where R 3  is an acetyl group. 
     
     
         10 . A compound as claimed in any one of  claims 1  to  9  where R 4  is SO 3 H or a salt form of SO 3 H. 
     
     
         11 . A compound as claimed in any one of  claims 1  to  10  where R 1  is a salt form of SO 3 H. 
     
     
         12 . A compound as claimed in any one of  claims 1  to  11  where A is an optionally substituted aryloxy group. 
     
     
         13 . A compound as claimed in  claim 1 , selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         14 . A compound as claimed in  claim 1 , selected from the group consisting of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         15 . A crystalline compound of formula 13, 14, 15, 16 or 27: 
       
         
           
           
               
               
           
         
       
     
     
         16 . A pharmaceutical composition comprising a pharmaceutically effective amount of a compound as claimed in any one of  claims 1  to  14  and optionally a pharmaceutically acceptable carrier, diluent or excipient. 
     
     
         17 . A method of treating or preventing a disease or disorder in which it is desirable to inhibit BACE-1 comprising administering a pharmaceutically effective amount of a compound as claimed in any one of  claims 1  to  14  to a patient requiring treatment. 
     
     
         18 . A method as claimed in  claim 17  where the disease or disorder is senile dementia, pre-senile dementia, multi-infarct dementia or Alzheimer's disease.