Sulphonyl compounds for use as linkers in solid phase and combinatorial synthesis

Abstract

The present invention relates to a linker shown by the following formula (I): X—S0 2 —R 1 —(A) m —R 2   (I) wherein R 1 is a group of the formula (A): [wherein R 3 , R 4 and R 5 are the same or different hydrogen, etc], etc, R 2 is a group which can form a chemical bond to a resin which may be protected by a conventional protective group, A is lower alkylene, etc, X is a leaving group, and m is an integer of 0 or 1, with proviso that A is (C 2 -C 6 )alkylene, and m is an integer of 1, when R 1 is a group of the formula (A).

1 . A linker of the following formula (I):  
       X—SO 2 —R 1 —(A) m —R 2   (I)  
       wherein 
 R 1  is a group of the formula (A), (B), (C), (D) and (E):  
                 

 [wherein 
 R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17  and R 18  are the same or different hydrogen, lower alkyl or lower alkoxy, and  
 
 n is an integer of 1 to 3],  
 
 R 2  is a group which can form a chemical bond to a resin which may be protected by a conventional protective group,  
 A is lower alkylene or a group of the formula:  
 —A 1 —O—A 2 —  (wherein A 1  and A 2  are each lower alkylene),    
 X is a leaving group, and  
 m is an integer of 0 or 1,  
 with proviso that A is (C 2 -C 6 )alkylene, and 
 m is an integer of 1,  
 when R 1  is a group of the formula (A),  
 or a salt thereof.  
 
 
     
     
         2 . A linker of    claim 1   , wherein 
 R 1  is a group of the formula (A) wherein 
 R 3 , R 4  and R 5  are each lower alkyl,  
   R 2  is a group which can form a chemical bond to a resin which may be protected by a conventional protective group,    A is (C 2 -C 4 )alkylene or a group of the formula:    —A 1 —O—A 2 — [wherein A 1  and A 2  are each (C 1 -C 4 )alkylene],      X is halogen,    m is an integer of 1.    
     
     
         3 . A linker of    claim 2   , wherein 
 R 1  is a group of the formula:  
                 
   R 2  is a group which can form a chemical bond to a resin which may be protected by a conventional protective group,    A is trimethylene,    X is chloro, and    m is an integer of 1.    
     
     
         4 . A linker of    claim 1   , wherein 
 R 1  is a group of the formula (B) wherein 
 R 6 , R 7 , R 8  and R 9  are each lower alkyl,  
 R 10  is hydrogen, and n is an integer of 3,  
   R 2  is a group which can form a chemical bond to a resin which may be protected by a conventional protective group,    A is (C 1 -C 4 )alkylene or a group of the formula:    —A 1 —O—A 2 —  [wherein A 1  and A 2  are each (C 1 -C 4 )alkylene],      X is halogen, and    m is an integer of 0 or 1.    
     
     
         5 . A linker of    claim 4   , wherein 
 R 1  is a group of the formula:  
                 
   R 2  is a group which can form a chemical bond to a resin which may be protected by a conventional protective group,    A is methylene or —(CH 2 ) 2 —O—CH 2 —,    X is chloro, and    m is an integer of 1.    
     
     
         6 . A linker of    claim 1   , wherein 
 R 1  is a group of the formula (B) wherein 
 R 6 , R 7 , R 8 , R 9  and R 10  are each lower alkyl, and  
 n is an integer of 3,  
   R 2  is a group which can form a chemical bond to a resin which may be protected by a conventional protective group,    A is (C 1 -C 4 )alkylene or a group of the formula:    —A 1 —O—A 2 — [wherein A 1  and A 2  are each (C 1 -C 4 )alkylene],      X is halogen, and    m is an integer of 0 or 1.    
     
     
         7 . A linker of    claim 6   , wherein 
 R 1  is a group of the formula:  
                 
   R 2  is a group which can form a chemical bond to a resin which may be protected by a conventional protective group,    X is chloro, and    m is an integer of 0, or    R 1  is a group of the formula:  
                 
   R 2  is a group which can form a chemical bond to a resin which may be protected by a conventional protective group,    A is methylene or —(CH 2 ) 2 —O—CH 2 —,    X is chloro, and    m is an integer of 1.    
     
     
         8 . A linker of    claim 1   , wherein 
 R 1  is a group of the formula (C) wherein 
 R 11 , R 12 , R 13 , R 14  are each lower alkyl, and  
 R 15  is hydrogen,  
   R 2  is a group which can form a chemical bond to a resin which may be protected by a conventional protective group,    A is (C 1 -C 4 )alkylene or a group of the formula:    —A 1 —A 2 —  [wherein A 1  and A 2  are each (C 1 -C 4 )alkylene],      X is halogen,    m is an integer of 1.    
     
     
         9 . A linker of    claim 8   , wherein 
 R 1  is a group of the formula:  
                 
   R 2  is a group which can form a chemical bond to a resin which may be protected by a conventional protective group,    A is methylene,    X is chloro, and    m is an integer of 1.    
     
     
         10 . A linker of    claim 1   , wherein 
 R 1  is a group of the formula (D) wherein 
 R 16  is lower alkyl,  
   R 2  is a group which can form a chemical bond to a resin which may be protected by a conventional protective group,    A is (C 1 -C 4 )alkylene or a group of the formula:    —A 1 —O—A 2 —  [wherein A 1  and A 2  are each (C 1 -C 4 )alkylene],      X is halogen,    m is an integer of 1.    
     
     
         11 . A linker of    claim 10   , wherein 
 R 1  is a group of the formula:  
                 
   R 2  is a group which can form a chemical bond to a resin which may be protected by a conventional protective group,    A is trimethylene,    X is chloro, and    m is an integer of 1.    
     
     
         12 . A linker of    claim 1   , wherein 
 R 1  is a group of the formula (E) wherein 
 R 17  and R 18  are each lower alkyl,  
   R 2  is a group which can form a chemical bond to a resin which may be protected by a conventional protective group,    A is (C 1 -C 4 )alkylene or a group of the formula:    —A 1 —O—A 2 — [wherein A 1  and A 2  are each (C 1 -C 4 )alkylene],      X is halogen,    m is an integer of 1.    
     
     
         13 . A linker of    claim 12   , wherein 
 R 1  is a group of the formula:  
                 
   R 2  is a group which can form a chemical bond to a resin which may be protected by a conventional protective group,    A is methylene,    X is chloro, and    m is an integer of 1.    
     
     
         14 . A derivative of the linker (I) of the present invention of the following formula:  
       AM—SO 2 —R 1 —(A) m —R 2    
       wherein AM is a residue of “amine compound”, and 
 R 1 , R 2 , A and m are each as defined in    claim 1   .