Oligomer-foscarnet conjugates

Abstract

The invention relates to (among other things) oligomer-foscarnet conjugates and related compounds. A conjugate of the invention, when administered by any of a number of administration routes, exhibits advantages over previously administered un-conjugated foscarnet compounds.

What is claimed is: 
     
         1 . A compound comprising a foscarnet residue covalently attached via a stable or degradable linkage to a water-soluble, non-peptidic oligomer. 
     
     
         2 . The compound of  claim 1 , having the following structure: 
       
         
           
           
               
               
           
         
         Wherein: X is a spacer moiety; and 
         POLY is a water-soluble, non-peptidic oligomer. 
       
     
     
         3 . The compound of  claim 1 , having the following structure: 
       
         
           
           
               
               
           
         
         Wherein: X is a spacer moiety; and 
         POLY is a water-soluble, non-peptidic oligomer. 
       
     
     
         4 . The compound of  claim 1 , having the following structure: 
       
         
           
           
               
               
           
         
         Wherein: R 2  is selected from the group consisting of substituted higher alkyl, unsubstituted higher alkyl, substituted higher alkenyl, unsubstituted higher alkenyl, substituted higher alkynyl, and unsubstituted higher alkynyl; 
         X is a spacer moiety; and 
         POLY is a water-soluble, non-peptidic oligomer. 
       
     
     
         5 . The compound of  claim 1 , having the following structure: 
       
         
           
           
               
               
           
         
         Wherein: R 2  is selected from the group consisting of substituted higher alkyl, unsubstituted higher alkyl, substituted higher alkenyl, unsubstituted higher alkenyl, substituted higher alkynyl, and unsubstituted higher alkynyl; 
         X is a spacer moiety; and 
         POLY is a water-soluble, non-peptidic oligomer. 
       
     
     
         6 . The compound of  claim 1 , having the following structure: 
       
         
           
           
               
               
           
         
         wherein: each R independently is selected from the group consisting of alkyl, cycloalkyl, alkylamino, aryl, arylamino, heteroaryl, and heterocycloalkyl; 
         R 2  is selected from the group consisting of substituted higher alkyl, unsubstituted higher alkyl, substituted higher alkenyl, unsubstituted higher alkenyl, substituted higher alkynyl, and unsubstituted higher alkynyl; 
         X is a spacer moiety; and 
         POLY is a water-soluble, non-peptidic oligomer. 
       
     
     
         7 . The compound of  claim 1 , wherein the foscarnet residue is a residue selected from the group consisting of a phosphonoformic acid, tri-sodium salt of phosphonoformic acid, and any pharmaceutically acceptable salt of phosphonoformic acid. 
     
     
         8 . The compound of any one of the preceding claims, wherein the water-soluble, non-peptidic oligomer is a poly(alkylene oxide). 
     
     
         9 . The compound of  claim 8 , wherein the poly(alkylene oxide) is a poly(ethylene oxide). 
     
     
         10 . The compound of any one of the preceding claims, wherein water-soluble, non-peptidic oligomer is made of between 1 and 30 monomers. 
     
     
         11 . The compound of  claim 10 , wherein the water-soluble, non-peptidic oligomer is made of between 1 and 10 monomers. 
     
     
         12 . The compound of  claim 8 , wherein the poly(alkylene oxide) includes an alkoxy or hydroxy end-capping moiety. 
     
     
         13 . The compound of any one of the preceding claims, wherein a single water-soluble, non-peptidic oligomer is attached to the foscarnet residue. 
     
     
         14 . The compound of any one of the preceding claims, wherein more than one water-soluble, non-peptidic oligomer is attached to the foscarnet residue. 
     
     
         15 . The compound of any one of the preceding claims, wherein the foscarnet residue is covalently attached via a stable linkage. 
     
     
         16 . The compound of any one of the preceding claims, wherein the foscarnet residue is covalently attached via a degradable linkage. 
     
     
         17 . The compound of any one of the preceding claims, wherein the linkage is an ether linkage. 
     
     
         18 . The compound of any one of the preceding claims, wherein the linkage is an ester linkage. 
     
     
         19 . A composition comprising a compound comprising a foscarnet residue covalently attached via a stable or degradable linkage to a water-soluble and non-peptidic oligomer, and optionally, a pharmaceutically acceptable excipient. 
     
     
         20 . A composition of matter comprising a compound comprising a foscarnet residue covalently attached via a stable or degradable linkage to a water-soluble, non-peptidic oligomer, wherein the compound is present in a dosage form. 
     
     
         21 . A method comprising covalently attaching a water-soluble, non-peptidic oligomer to a foscarnet. 
     
     
         22 . A method of treatment comprising administering a compound comprising a foscarnet residue covalently attached via a stable or degradable linkage to a water-soluble, non-peptidic oligomer to a subject in need thereof.