Oxazolidinone containing dimer compounds, compositions and methods to make and use

Abstract

Dosage forms or pharmaceutical compositions comprise a compound having the structure of Formula IV: wherein n is a non-negative integer; wherein each Z is an oxazolidinone-containing moiety having antibiotic activity in vivo upon cleaving, wherein M is independently OR 1 or NR 1 R 2 ; wherein R 1 and R 2 are independently selected from the group consisting of H, an optionally-substituted hydrocarbyl residue or a pharmaceutically acceptable cation; wherein the compound in the dosage form or a pharmaceutical composition is present in an amount effective for treating or preventing an antibacterial infection in a mammalian subject. Methods of preparing and using these dosage forms or pharmaceutical compositions are also disclosed.

What is claimed is: 
     
         1 . A dosage form or a pharmaceutical composition comprising a therapeutically effective amount of compound having the structure of Formula IV: 
       
         
           
           
               
               
           
         
         wherein n is 0, 1 or 2; 
         wherein each Z is an oxazolidinone-containing moiety having antibiotic activity in vivo upon cleaving, 
         wherein M is independently OR 1  or NR 1 R 2 ; 
         wherein R 1  and R 2  are independently selected from the group consisting of H, an optionally-substituted hydrocarbyl residue that may contain one or more heteroatoms or a pharmaceutically acceptable cation. 
       
     
     
         2 . The dosage form or the pharmaceutical composition of  claim 1 , wherein each Z is 
       
         
           
           
               
               
           
         
         wherein * is the point of attachment of Z to P; 
         wherein R 1 a and R 1 b are independently selected from H and F, provided that at least one of R 1 a and R 1 b is F, and 
         Het is an optionally-substituted five- or six-membered heterocycle comprising at least one N, O, or S atom. 
       
     
     
         3 . The dosage form or the pharmaceutical composition of  claim 2 , wherein the compound has the structure 
       
         
           
           
               
               
           
         
         wherein M is OR 1  and R 1  is a pharmaceutically-acceptable cation. 
       
     
     
         4 . The dosage form or the pharmaceutical composition of  claim 3   wherein R 1  is a nitrogen-containing cation.   
     
     
         5 . The dosage form or the pharmaceutical composition of  claim 3   wherein R 1  is an imidazolium cation.   
     
     
         6 . The dosage form or the pharmaceutical composition of  claim 3   wherein each Z is   
       
         
           
           
               
               
           
         
       
     
     
         7 . The dosage form or the pharmaceutical composition of  claim 6 ,
 wherein each Z is   
       
         
           
           
               
               
           
         
       
     
     
         8 . The dosage form or the pharmaceutical composition of  claim 1 , wherein the dosage form or the pharmaceutical composition is a pharmaceutical composition further comprising a pharmaceutically acceptable carrier, diluent or excipient. 
     
     
         9 . The dosage form or the pharmaceutical composition of  claim 1 , wherein each Z has R stereochemistry. 
     
     
         10 . The dosage form or the pharmaceutical composition of  claim 5 , wherein each Z is 
       
         
           
           
               
               
           
         
       
     
     
         11 . The dosage form or the pharmaceutical composition of  claim 2 , which is 
       
         
           
           
               
               
           
         
         or pharmaceutically acceptable salt thereof. 
       
     
     
         12 . The dosage form or the pharmaceutical composition of  claim 11 , wherein Het is tetrazolyl. 
     
     
         13 . A method of preparing the compound in the dosage form or pharmaceutical composition of  claim 1 , comprising the step of treating a compound of the formula Z—H with a phosphorylating agent. 
     
     
         14 . A method of preparing the compound in the dosage form or pharmaceutical composition of  claim 1 , comprising the step of treating with a dehydrating agent of the compound Z—P′, wherein P′ is a mono- or dihydrogen phosphate group. 
     
     
         15 . The method of  claim 13 , wherein the phosphorylating agent is POCl 3 . 
     
     
         16 . A method of treating a bacterial infection comprising
 administering the dosage form or the pharmaceutical composition of  claim 1  to a subject in need thereof.   
     
     
         17 . A method of treating a bacterial infection comprising
 administering the dosage form or the pharmaceutical composition of  claim 12  to a subject in need thereof.