Perturbed membrane-binding compounds and methods of using the same

Abstract

The invention relates to compounds that selectively bind to cells undergoing perturbations and alterations of their normal plasma membrane organization, i.e., cells undergoing cell death, apoptotic cells or activated platelets. The invention further provides methods for utilizing the compounds in medical practice, for diagnostic and therapeutic purposes.

1 . A compound represented by the structure as set forth in formula (I): 
       
         
           
           
               
               
           
         
         including pharmaceutically acceptable salts, hydrates, solvates and metal chelates of the compound represented by the structure as set forth in formula (I) and solvates and hydrates of the salts; wherein, one of R or R′ groups is hydrogen, and the other of R or R′ group represents C 1 , C 2 , C 3 , C 4 , C 5 , C 6 , C 7 , C 8 , C g , C 10 , C 11 , C 12 , C 13 , C 14 , C 15 , C 16 , linear or branched alkyl, linear or branched hydroxy-alkyl, linear or branched fluoro-alkyl, aryl or hetroaryl composed of one or two rings, or combinations thereof; n and m each stands for an integer of 0, 1, 2, 3 or 4; n and m may be same or different; M is selected from null, hydrogen, —O—, —S—, and —N(U), wherein U stands for hydrogen, or C 1 , C 2 , C 3 , or C 4  alkyl; x, and z each stands independently and is an integer of 0, 1 or 2, where x and z can be the same or different; y is an integer of 0, 1 or 2, where when y=2 the substituent R′ may be the same or different at each occurrence; and D is hydroxyl. 
       
     
     
         2 . The compound according to  claim 1  represented by the structure as set forth in formula (V): 
       
         
           
           
               
               
           
         
         wherein J represents OH and r stands for an integer of 3, 4, 5, 6, 7 or 8. 
       
     
     
         3 . The compound according to  claim 2 , wherein r is 4. 
     
     
         4 . The compound according to  claim 2 , wherein r is 5. 
     
     
         5 . The compound according to  claim 2 , wherein the functional groups of the compound are protected by protecting groups. 
     
     
         6 . The compound according to  claim 5 , wherein the protecting groups comprise tert-butyl or ethyl. 
     
     
         7 . A method for radio-labeling the compound represented by a structure as set forth in formula (V), 
       
         
           
           
               
               
           
         
         wherein J represents OH and r stands for an integer of 3, 4, 5, 6, 7 or 8, the method comprising replacing J with a radio-isotope, thereby radio-labeling the compound represented by a structure as set forth in formula (V). 
       
     
     
         8 . The method according to  claim 7 , wherein r is 4. 
     
     
         9 . The method according to  claim 7 , wherein r is 5. 
     
     
         10 . The method according to  claim 7  comprising protecting the functional groups of the compound with protecting groups. 
     
     
         11 . The method according to  claim 9 , wherein the protecting groups comprise tert-butyl or ethyl. 
     
     
         12 . The method according to  claim 9  comprising removing the protecting groups after the step of replacing J with a radio-isotope. 
     
     
         13 . The method according to  claim 7 , wherein the radio-isotope is  18 F.