Liver targeted conjugates

Abstract

Therapeutic conjugates containing a statin or a modified statin (collectively “statin”) linked to a therapeutic agent (also referred to as a drug herein) are targeted to the liver by the statin or modified statin and thereby deliver the therapeutic agent to liver cells.

1 - 56 . (canceled) 
   
   
       57 . A compound comprising an HMG-CoA reductase inhibitor and a linker suitable for covalent attachment of a selected compound. 
   
   
       58 . The compound of  claim 57  wherein the HMG-CoA reductase inhibitor is a statin. 
   
   
       59 . The compound of  claim 57  having the formula: 
     
       
         
         
             
             
         
       
     
     wherein
 R is: H, a C 1  to C 6  alkyl, alkenyl or alkynl optionally substituted with one or more —OH or halogen; 
 n is 1, 2, 3, 4, 5, or 6; 
 X is S, O or N; 
 R 3  and R 4  are independently selected from —CH 3 , —OH, H, —CH 2 CH 3 , cyclopropyl and a halogen; 
 R 1  and R 5  are independently selected from —CH 3  and H; 
 R 2  is selected from: 
 
     
       
         
         
             
             
         
       
     
   
   
       60 . The compound of  claim 59  having the formula: 
     
       
         
         
             
             
         
       
     
   
   
       61 . A compound comprising a HMG-CoA reductase inhibitor covalently attached to a therapeutic agent through a linker. 
   
   
       62 . The compound of  claim 61  wherein the HMG-CoA reductase inhibitor is a statin. 
   
   
       63 . The compound of  claim 61  wherein the therapeutic agent is selected from the group consisting of: niacin, an angiotensin inhibitor, colchicine, a corticosteroid, an endothelin inhibitor, interferon-α, IL-10, interferon-β, pentoxifylline, phosphotidylcholine, a PPAR antagonist, S-adenosyl-methionine, and tocoherol. 
   
   
       64 . The compound of  claim 61  having the formula: 
     
       
         
         
             
             
         
       
     
     wherein R is a therapeutic agent;
 n is 1, 2, 3, 4, 5, or 6; 
 X is S, O or N; 
 R 3  and R 4  are independently selected from —CH 3 , —OH, —CH 2 CH 3 , cyclopropyl and a halogen; 
 R 1  and R 5  are independently selected from —CH 3  and H; 
 R 2  is selected from 
 
     
       
         
         
             
             
         
       
     
   
   
       65 . The compound of  claim 64  having the structure: