Boron-containing small molecules

Abstract

This invention relates to, among other items, benzoxaborole compounds and their use for treating bacterial infections.

What is claimed is: 
     
         1 . A compound having a structure which is: 
       
         
           
           
               
               
           
         
         wherein R 3  is —CH 2 NH 2 ; 
         R 4  is selected from the group consisting of halogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, and sec-butoxy; 
         Y is O; and 
         R 5  is 
       
       
         
           
           
               
               
           
         
         wherein a is 2, 3 or 4; 
         R 10  and R 11  is H; and 
         R 12  is selected from the group consisting of H, OH, NH 2 , methyl, ethyl, —NHS(O) 2 CH 3 , cyano, —NHC(O)CH 3 , —NHC(O)NHCH 2 CH 3 , —C(O)NH 2 , —C(O)OH, 4-(methoxy)phenyl, benzyl, benzoxy, —NHC(O)OCH 2 Ph, —C(O)NHCH 2 CH 2 OH and —C(NH 2 )(NH); 
         or a salt, hydrate or solvate thereof. 
       
     
     
         2 . The compound of  claim 1  or a salt, hydrate or solvate thereof, having a structure which is: 
       
         
           
           
               
               
           
         
         wherein C* is a carbon atom stereocenter which has a configuration which is (R) or (S). 
       
     
     
         3 . The compound of  claim 2  or a salt, hydrate or solvate thereof, wherein the C* stereocenter is in a (S) configuration. 
     
     
         4 . The compound of  claim 1  or a salt, hydrate or solvate thereof, wherein R 4  is selected from the group consisting of fluorine, chlorine, bromine, and iodine. 
     
     
         5 . The compound of  claim 1  or a salt, hydrate or solvate thereof, wherein R 4  is selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl. 
     
     
         6 . A composition comprising:
 a) a first stereoisomer of the compound of  claim 3  or a salt, hydrate or solvate thereof,   b) at least one additional stereoisomer of the first stereoisomer;   wherein the first stereoisomer is present in an enantiomeric excess of at least 80% relative to said at least one additional stereoisomer.   
     
     
         7 . A combination comprising the compound of  claim 1 , or a pharmaceutically acceptable salt thereof, together with at least one other therapeutically active agent. 
     
     
         8 . A pharmaceutical formulation comprising:
 a) the compound of  claim 1 , or a pharmaceutically acceptable salt thereof, and   b) a pharmaceutically acceptable excipient.   
     
     
         9 . A method of inhibiting the editing domain of a t-RNA synthetase, comprising: contacting the synthetase with an effective amount of a compound of  claim 1 , or a pharmaceutically-acceptable salt thereof, thereby inhibiting the synthetase. 
     
     
         10 . The method of  claim 9 , wherein the t-RNA synthetase is LeuRS. 
     
     
         11 . A method of killing and/or preventing the growth of a microorganism, comprising: contacting the microorganism with an effective amount of the compound of  claim 1 , thereby killing and/or preventing the growth of the microorganism. 
     
     
         12 . The method of  claim 11 , wherein the microorganism is  Mycobacterium tuberculosis.    
     
     
         13 . A method of treating and/or preventing a disease in an animal, comprising: administering to the animal a therapeutically effective amount of the compound of  claim 1 , or a pharmaceutically-acceptable salt thereof, thereby treating and/or preventing the disease. 
     
     
         14 . The method of  claim 13 , wherein the disease is tuberculosis 
     
     
         15 . The method of  claim 13 , wherein the animal is a human.