Sugar Derivatives Comprising Sulfur-Containing Moieties And Methods Of Making Same And Methods Of Using The Same For The Treatment Of MPS IIIC

Abstract

Described herein are modified sugar, iminosugar and azasugar compounds and methods of making same. One or more of these modified compounds contain sulfates, sulfites, sulfamates and/or sulfonamides. Also described are pharmaceutical compositions/formulations comprising these compounds, as well as methods using these modified sugar compounds for the treatment of MPS IIIC (also known as Sanfilippo Type C).

What is claimed is: 
     
         1 . A compound having a structure represented by formula I or II: 
       
         
           
           
               
               
           
         
         wherein: A 1  is —COR 2 , —SO 2 R 2 , —CONR 2 R 3 , —SO 2 NR 2 R 3 ;
 R 1 , R 2 , R 3  are each independently H, arylalkyl, aryl, or C 1-4  alkyl; and 
 X is —OH or —NR 1 R 2 ; or 
 
         a pharmaceutically acceptable salt, solvate, or prodrug thereof. 
       
     
     
         2 . The compound of  claim 1 , wherein the compound has a structure represented by formula Ia: 
       
         
           
           
               
               
           
         
       
       or
 a pharmaceutically acceptable salt, solvate, or prodrug thereof. 
 
     
     
         3 . A compound having a structure represented by formula III or IV: 
       
         
           
           
               
               
           
         
         wherein: A 1  is —COR 2 , —SO 2 R 2 , —CONR 2 R 3 , —SO 2 NR 2 R 3 ;
 R 1 , R 2  and R 3  are each independently H, arylalkyl, aryl, or C 1-4  alkyl; 
 X and Y are each independently O or a lone pair of electrons; and 
 each Z is independently O or NH; or 
 
         a pharmaceutically acceptable salt, solvate, or prodrug thereof. 
       
     
     
         4 . The compound of  claim 3 , wherein the compound has a structure represented by formula IIIa: 
       
         
           
           
               
               
           
         
       
       or
 or a pharmaceutically acceptable salt, solvate, or prodrug thereof. 
 
     
     
         5 . The compound of  claim 3 , wherein the compound has a structure represented by formula IIIb: 
       
         
           
           
               
               
           
         
       
       or
 or a pharmaceutically acceptable salt, solvate, or prodrug thereof. 
 
     
     
         6 . A compound have a structure represented by any of formulae (V)-(XI): 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or
 or a pharmaceutically acceptable salt, solvate, or prodrug thereof. 
 
     
     
         7 . A pharmaceutical composition comprising:
 a. the compound of  claim 1 ; and   b. at least one pharmaceutically acceptable carrier.   
     
     
         8 . A method of making a pharmaceutical composition according to  claim 7 , the method comprising, adding to at least one pharmaceutically acceptable carrier to the compound of  claim 1 . 
     
     
         9 . A method of making the compound according to  claim 4 , the method comprising reacting N-benzyl(N-acetyl 1,2 deoxynojiimycin) with SOCl 2  and pyridine. 
     
     
         10 . A method of making the compound having a structure represented by formula (V) according to  claim 6 , the method comprising
 a. reacting 1-deoxygalactonojirimycin with EtOCOCl to produce an intermediate; and   b. reacting the intermediate with SO 2 Cl and pyridine.   
     
     
         11 . A method of making the compound having a structure represented by formula (VI) according to  claim 6 , the method comprising
 a. reacting 1-deoxygalactonojirimycin with EtOCOCl to produce an intermediate; and   b. reacting the intermediate with SO 2 Cl 2  and pyridine.   
     
     
         12 . A method of making the compound having a structure represented by formula (VII) according to  claim 6 , the method comprising
 a. reacting 1-deoxynojirimycin with EtOCOCl to produce an intermediate; and   b. reacting the intermediate with SO 2 Cl 2  and pyridine.   
     
     
         13 . A method of making the compound having a structure represented by formula (X) according to  claim 6 , the method comprising
 a. reacting a compound having a structure represented by:   
       
         
           
           
               
               
           
         
         
           with MsCl and NET 3  to produce an intermediate; and 
         
         b. reacting the intermediate with HCl. 
       
     
     
         14 . A method of making the compound having a structure represented by formula (XI) according to  claim 6 , the method comprising
 a. reacting a compound having a structure represented by:   
       
         
           
           
               
               
           
         
         
           with LiN 3  to produce an intermediate; and 
         
         b. reacting the intermediate with Pd/C and H 2 , MeSO 2 Cl and NEt 3 , and HCl. 
       
     
     
         15 . A method of making the compound having a structure represented by formula (IX) according to  claim 6 , the method comprising reacting a compound having a structure represented by: 
       
         
           
           
               
               
           
         
         with SO 2 Cl and pyridine. 
       
     
     
         16 . A method of making the compound having a structure represented by formula (VIII) according to  claim 6 , the method comprising reacting a compound having a structure represented by: 
       
         
           
           
               
               
           
         
         with SO 2 Cl and pyridine. 
       
     
     
         17 . A method of preventing and/or treating MPS IIIC, the method comprising administering to a patient in need thereof a therapeutically effective amount of the compound of  claim 1 . 
     
     
         18 . The method of  claim 17 , further comprising administering an effective amount of a second therapeutic agent comprising a recombinant MPS IIIC enzyme. 
     
     
         19 . A kit comprising:
 a. a container having an effective amount of the compound of  claim 1 ; and   b. instructions for using the same to prevent and/or treat MPS IIIC.   
     
     
         20 . The kit of  claim 19 , further comprising an effective amount of a second therapeutic agent comprising a recombinant MPS IIIC enzyme.