Oxazolidinone combinatorial libraries, compositions and methods of preparation

Abstract

Oxazolidinones and methods for their synthesis are provided. Also provided are combinatorial libraries comprising oxazolidinones, and methods to prepare the libraries. Further provided are methods of making biologically active oxazolidinones as well as pharmaceutically acceptable compositions comprising the oxazolidinones. The methods of library preparation include the attachment of oxazolidinones to a solid support. The methods of compound preparation in one embodiment involve the reaction of an iminophosphorane with a carbonyl containing polymeric support.

1 . A compound of the structure 1b:  
       
         
           
           
               
               
           
         
       
       a its pharmaceutically acceptable salt thereof wherein 
 R 2 , R 3 , R 4  and R 5  are, independently, hydrogen alkyl, heteroalkyl, heteroaryl or an electron withdrawing group;  
 R 6  is acyl or sulfonyl; and,  
 R 1  is one of the following functional groups:  
 C(O)R 10 , wherein R 10  is hydrogen, alkyl, heteroalkyl, aryl or heteroaryl;  
 SR 11 , wherein R 11  is hydrogen, alkyl, heteroalkyl, aryl or heteroaryl;  
 S(O) 2 R 11 , wherein R 11  is hydrogen, alkyl, heteroalkyl, aryl or heteroaryl;  
 S(O)R 11 , wherein R 11  is hydrogen, alkyl, heteroalkyl, aryl or heteroaryl;  
 NR 12 R 13 , wherein R 12  and R 13  are, independently, hydrogen, acyl, sulfonyl, alkyl, heteroalkyl, aryl or heteroaryl;  
 2-oxazolyl, wherein R 14  is at the 4-position and R 15  is at the 5-position of the oxazolyl, and wherein R 14  and R 15  are, independently, hydrogen, alkyl, heteroalkyl, aryl, heteroaryl or an electron withdrawing group;  
 2-aminothiazolyl, wherein R 16  is at the 4-position and R 17  is at the 5-position of the thiazole, and wherein R 16  and R 17 , are, independently, hydrogen, alkyl, heteroalkyl, aryl, heteroaryl or an electron withdrawing group; and  
 CH 2 NR 18 R 19 , wherein R 18  and R 19  are, independently, hydrogen, alkyl, heteroalkyl, aryl, heteroaryl, acyl or sulfonyl.  
 
     
     
         2 . A compound according to  claim 1  wherein R 1  is C(O)R 10 .  
     
     
         3 . A compound according to  claim 2  wherein R 10  is aryl or heteroalkyl.  
     
     
         4 . A compound according to  claim 1 , wherein R 1  is SR 11 .  
     
     
         5 . A compound according to  claim 4  wherein R 11  is aryl or heteroalkyl.  
     
     
         6 . A compound of  claim 1  wherein R 1  is S(O) 2 R 11  or S(O)R 11 .  
     
     
         7 . A compound according to  claim 6  wherein R 11  is aryl.  
     
     
         8 . A compound according to  claim 7  wherein R 11  is heteroalkyl.  
     
     
         9 . A compound of  claim 1  wherein R 1  is NR 12 R 13 .  
     
     
         10 . A compound according to  claim 1 , wherein R 3 , R 4  and R 5  are hydrogen; and R 2  is fluorine.  
     
     
         11 . The compound of  claim 1  which is  
       
         
           
           
               
               
           
         
       
     
     
         12 . The compound of  claim 1  which is  
       
         
           
           
               
               
           
         
       
     
     
         13 . The compound of  claim 1  which is  
       
         
           
           
               
               
           
         
       
     
     
         14 . The compound of  claim 1  which is  
       
         
           
           
               
               
           
         
       
     
     
         15 . The compound of  claim 1  which is  
       
         
           
           
               
               
           
         
       
     
     
         16 . A method for treating or preventing an infectious disorder in a human or an animal comprising administering to the subject an effective amount of a compound of  claim 1 .  
     
     
         17 . A composition for the treating or preventing of an infectious disorder in a human or an animal comprising an effective amount of a compound of  claim 1  and a pharmaceutically acceptable carrier.