Inositol and trehalose derivatives and pharmaceutical compositions for treating neurodegenerative diseases comprising the same

Abstract

The invented inositol and trehalose derivatives, prepared by introducing multiple units of the guanidine group to the backbone molecules, show excellent blood-brain barrier permeability, and accordingly, it can be easily transported to the brain tissues and utilized for the treatment of neurodegenerative diseases such as Alzheimer's disease and Huntington's disease.

1 . Inositol derivatives of Formula (1) or salts thereof: 
       
         
           
           
               
               
           
         
         wherein, 
         R is 
       
       
         
           
           
               
               
           
         
       
       n being an integer in the range of 1 to 12; and
 R 1  is hydrogen, alkyl or —COR′, R′ being hydrogen, alkyl, aminoalkyl, arylalkyl, cycloalkyl or heteroalkyl. 
 
     
     
         2 . The inositol derivatives of  claim 1 , wherein the stereochemistry of the compound of Formula (1) corresponds to the scyllo-, myo-, epi-, chino-, allo-, muco-, neo- or cis-inositol isomer, or salts thereof. 
     
     
         3 . Inositol derivatives of Formula (2) or salts thereof: 
       
         
           
           
               
               
           
         
         wherein, 
         R is 
       
       
         
           
           
               
               
           
         
       
       n being an integer in the range of 1 to 12; and
 R 1  and R 2  are each independently hydrogen, alkyl or —COR′, R′ being hydrogen, alkyl, aminoalkyl, arylalkyl, cycloalkyl or heteroalkyl. 
 
     
     
         4 . The inositol derivatives of  claim 3 , wherein the structural framework of the compound of Formula (2) corresponds to the scyllo-, myo-, epi-, or chino-inositol isomer, or salts thereof. 
     
     
         5 . Trehalose derivatives of Formula (3) or salts thereof: 
       
         
           
           
               
               
           
         
         wherein, 
         R is 
       
       
         
           
           
               
               
           
         
       
       n being an integer in the range of 1 to 12; and
 R 1  is hydrogen, R, alkyl or —COR′, R′ being hydrogen, alkyl, aminoalkyl, arylalkyl, cycloalkyl, heteroalkyl or a phosphor. 
 
     
     
         6 . Monosaccharide derivatives of Formula (4) or salts thereof; 
       
         
           
           
               
               
           
         
         wherein, 
         R is 
       
       
         
           
           
               
               
           
         
       
       n being an integer in the range of 1 to 12;
 R 1  is hydrogen, R, alkyl, arylalkyl, cycloalkyl or heteroalkyl; and 
 R 2  is hydrogen, R or trityl. 
 
     
     
         7 . The monosaccharide derivatives of  claim 6 , wherein the compound of Formula (4) has the structural framework of D-glucose, D-mannose, D-allose or D-galactose, or salts thereof. 
     
     
         8 . Pharmaceutical compositions for treating neurodegenerative diseases, containing the compound according to  claim 1  as an effective component. 
     
     
         9 . The pharmaceutical compositions of  claim 8 , wherein the neurodegenerative diseases include Alzheimer's disease, Huntington's disease, and other closely related diseases. 
     
     
         10 . Pharmaceutical compositions for treating neurodegenerative diseases, containing the compound according to  claim 2  as an effective component. 
     
     
         11 . Pharmaceutical compositions for treating neurodegenerative diseases, containing the compound according to  claim 3  as an effective component. 
     
     
         12 . Pharmaceutical compositions for treating neurodegenerative diseases, containing the compound according to  claim 4  as an effective component. 
     
     
         13 . Pharmaceutical compositions for treating neurodegenerative diseases, containing the compound according to  claim 5  as an effective component. 
     
     
         14 . Pharmaceutical compositions for treating neurodegenerative diseases, containing the compound according to  claim 6  as an effective component. 
     
     
         15 . Pharmaceutical compositions for treating neurodegenerative diseases, containing the compound according to  claim 7  as an effective component.