Antimicrobial ortho-fluorophenyl oxazolidinones for treatment of bacterial infections

Abstract

The present invention provides certain ortho-fluorophenyl oxazolidinones of the following formula I: or pharmaceutically acceptable salts or prodrugs thereof that are antibacterial agents, pharmaceutical compositions containing them, methods for their use, and methods for preparing these compounds.

1 . A compound of the following formula II 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof wherein:
 R 1  is selected from the group consisting of —CH 2 OH, —CONH 2 , —CONHMe, —CH 2 NHC(═O)Me, —CH 2 NHC(═O)Et, —CH 2 NHC(═O)OMe, (4-R 7 -1,2,3-triazol-1-yl)methyl, (5-R 7 -isoxazol-3-yl)aminomethyl, and (5-R 7 -isoxazol-3-yl)oxymethyl; and 
 R 2 , R 3  and R 4  is are independently H or F; and 
 
       
         
           
           
               
               
           
         
         R 7  is H, C 1-4 alkyl, halo or —CN. 
       
     
     
         2 . The compound of  claim 1 , wherein R 2  is H, and R 3  and R 4  are independently selected from H and F. 
     
     
         3 . A The compound of  claim 1 , wherein R 1  is —CH 2 (1,2,3-triazol-1-yl), —CH 2 (4-methyl-1,2,3-triazol-1-yl), —CH 2 NH(isoxazol-3-yl) or —CH 2 O(isoxazol-3-yl). 
     
     
         4 . (canceled) 
     
     
         5 . The compound of  claim 1  selected from: 
       
         
           
           
               
               
           
         
       
     
     
         6 . The compound of  claim 1  selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         7 . The compound of  claim 1  selected from the structures: 
       
         
           
           
               
               
           
         
       
     
     
         8 - 15 . (canceled) 
     
     
         16 . A method for the treatment of a microbial infection in a mammal comprising administering to the mammal in need thereof a therapeutically effective amount of a compound of  claim 1 . 
     
     
         17 . The method according to  claim 16 , wherein the compound is administered to the mammal orally, parenterally, transdermally, topically, rectally, or intranasally in a pharmaceutical composition. 
     
     
         18 . The method according to  claim 16 , wherein the compound is administered once-daily in an amount of from about 1 to about 75 mg/kg of body weight/day. 
     
     
         19 . The method according to  claim 16 , wherein the microbial infection is a gram-positive microbial infection. 
     
     
         20 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of  claim 1  and a pharmaceutically acceptable carrier.