Oligomer-calcium channel blocker conjugates

Abstract

The invention provides small molecule drugs that are chemically modified by covalent attachment of a water soluble oligomer. A conjugate of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from the characteristics of the small molecule drug not attached to the water soluble oligomer.

1 - 3 . (canceled) 
     
     
         4 . A compound having the following structure: 
       
         
           
           
               
               
           
         
       
       wherein:
 R is hydrogen or lower alkyl; 
 R 1  and R 2  are each independently selected from the group consisting of hydrogen, substituted lower alkyl, unsubstituted lower alkyl, and —YOYNR 6 R 7 , where each Y is independently lower alkylene and R 6  and R 7  are each independently selected from the group consisting of hydrogen, unsubstituted lower alkyl, substituted lower alkyl, cycloalkyl, aryl and alkylaryl; 
 R 3  is selected from the group consisting of hydrogen, unsubstituted lower alkyl, substituted lower alkyl, and —YNR 6 R 7 , where Y is lower alkylene and R 6  and R 7  are each independently selected from the group consisting of hydrogen, unsubstituted lower alkyl, substituted lower alkyl, cycloalkyl, aryl and alkylaryl; 
 R 5  is independently selected from the group consisting of hydrogen, unsubstituted lower alkyl, substituted lower alkyl, chloro, fluoro and nitro; 
 each X is independently a spacer moiety; and 
 each POLY is independently a water-soluble oligomer wherein the number of monomers in the water-soluble oligomer is between 2 and 30. 
 
     
     
         5 - 17 . (canceled) 
     
     
         18 . The compound of  claim 4 , wherein the water-soluble oligomer is a poly(alkylene oxide). 
     
     
         19 . The compound of  claim 18 , wherein the poly(alkylene oxide) is a poly(ethylene oxide). 
     
     
         20 . (canceled) 
     
     
         21 . The compound of  claim 4 , wherein the number of monomers in the water-soluble oligomer is between 2 and 10 monomers. 
     
     
         22 . The compound of  claim 18 , wherein the poly(alkylene oxide) includes an alkoxy or hydroxy end-capping moiety. 
     
     
         23 - 32 . (canceled) 
     
     
         33 . The compound of  claim 4 , having the following structure 
       
         
           
           
               
               
           
         
       
       wherein each (n) is an integer between 2 to 30. 
     
     
         34 . The compound of  claim 33 , wherein each (n) is 3.