Bone targeted therapeutics and methods of making and using the same

Abstract

The present invention provides novel bisphosphonate conjugates, pharmaceutical compositions comprising bisphosphonate conjugates and methods of using such analogs in the treatment of bone cancer, bone-related diseases, bone infection, bone inflammation, and diseases of the soft tissues surrounding bones.

What is claimed is: 
     
         1 . A bisphosphonate conjugate comprising: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable acid addition salt thereof wherein,
 X is O; 
 V is O or S; 
 Y is a residue of an anti-infective compound in a class selected from the group consisting of fluoroquinolones, lincosamides, oxazolidinones, aminoglycosides, cephalosporins, and glycopeptides; 
 R 1  is selected from the group consisting of OH, SH, NH 2 , OZ, SZ, NZ, halogen, and H; 
 R 2  is selected from the group consisting of H, Z, and halogen; and 
 Z is selected from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, and NH 2 . 
 
     
     
         2 . The conjugate of  claim 1 , wherein the anti-infective compound belongs to the fluoroquinolone class. 
     
     
         3 . The conjugate of  claim 1 , wherein the anti-infective compound belongs to the lincosamide class. 
     
     
         4 . The conjugate of  claim 1 , wherein the anti-infective compound belongs to the oxazolidinone class. 
     
     
         5 . The conjugate of  claim 1 , wherein the anti-infective compound belongs to the aminoglycoside class. 
     
     
         6 . The conjugate of  claim 1 , wherein the anti-infective compound belongs to the cephalosporin class. 
     
     
         7 . The conjugate of  claim 1 , wherein the anti-infective compound belongs to the glycopeptide class. 
     
     
         8 . A pharmaceutical composition comprising a conjugate of  claim 1  and a pharmaceutically-acceptable carrier. 
     
     
         9 . A method of treating bone infection, the method comprising administering a therapeutically effective amount of a conjugate of  claim 1  to a subject in need thereof. 
     
     
         10 . A method of delivering an anti-infective compound to the bone or surrounding tissue, wherein the anti-infective compound is in a class selected from the group consisting of fluoroquinolones, lincosamides, oxazolidinones, aminoglycosides, cephalosporins, and glycopeptides, the method comprising administering a conjugate of  claim 1  to a subject in need thereof. 
     
     
         11 . A method of affecting bone growth in mammals, the method comprising administering to a mammal requiring a change in bone growth a therapeutically effective amount of a conjugate of  claim 1 . 
     
     
         12 . A method of treating inflammation caused by bone infection, the method comprising administering a therapeutically effective amount of a conjugate of  claim 1 .