AI-2 compounds and analogs based on Salmonella typhimurium LsrB structure

Abstract

This invention relates to crystals comprising apo-LsrB and holo-LsrB. The structure of holo-LsrB identifies a tetrahydroxytetrahydrofuran derived from 4,5-dihydroxy-2,3-pentanedione (DPD) as the active autoinducer-2 (AI-2) molecule in Salmonella typhimurium . The X-ray crystallographic data can be used in a drug discovery method. Additionally the invention provides AI-2 analogs based on this discovery as well as pharmaceutical compositions containing those analogs.

1 - 3 . (canceled) 
     
     
         4 . A compound represented by formula I or formula J: 
       
         
           
           
               
               
           
         
         wherein Y is hydrogen or hydroxyl; and
 R is lower alkyl; 
 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         5 . (canceled) 
     
     
         6 . A compound represented by formula K or formula L: 
       
         
           
           
               
               
           
         
         wherein
 Y is hydrogen or hydroxyl; 
 X and Z are independently hydrogen, lower alkyl or hydroxyl; and 
 R is lower alkyl; 
 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         7 - 9 . (canceled) 
     
     
         10 . A pharmaceutical composition comprising one or more compounds of  claim 4  in admixture with a pharmaceutically acceptable carrier. 
     
     
         11 . A pharmaceutical composition comprising one or more compounds of  claim 6  in admixture with a pharmaceutically acceptable carrier. 
     
     
         14 - 39 . (canceled)