Modulation of pathogenicity

Abstract

The present invention relates to the use of compounds of the general Formula (I): wherein in Formula (I), R is H, alkyl, cycloalkyl, aryl or heteroaryl; R 1 is H, alkyl, cycloalkyl, aryl or heteroaryl; R 2 is H, alkyl, cycloalkyl, aryl or heteroaryl; A 1 and A 2 each independently represent an optionally substituted C 1 -C 20 -alkyl group which may contain one or more group(s) Z, or a monocyclic or polycyclic optionally substituted aromatic or non-aromatic ring system which may contain one or more group(s) X, and in case of a polycyclic ring system, said system contains at least one aromatic ring; Z is selected from the group consisting of S, O, N, NR 4 , CO, CO 2 , CS, SO or SO 2 X is selected from the group consisting of S, O, N; NR 4 , SO or SO 2 ;

1 . A compound of Formula (I) 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or physiologically functional derivative thereof, wherein 
         A 1  is alkyl, aryl, or heteroaryl, each of which may be optionally substituted with one or more R 3 ; 
         p is 0 or 1; 
         Y 1  is —C(O)— or —C(S)—; 
         R 1  is H or alkyl, cycloalkyl, aryl, or heteroaryl, each of which may be optionally substituted with one or more R 3 ; 
         n is 1; 
         R 2  is H or alkyl, cycloalkyl, aryl, or heteroaryl, each of which may be optionally substituted with one or more R 3 ; 
         Y 2  is —C(O)— or —C(S)—; 
         A 2  is a benzothienyl, optionally substituted with one or more R 3 ; 
         each R 3  independently is OR 4 , SR 4 , hydroxyalkyl, hydroxyalkylamino, cycloalkyl, halogen, haloalkyl, haloalkoxy, NO 2 , CN, SO 2 NR 4 R 5 , CO 2 NR 4 R 5 , COR 4 , CO 2 R 4 , SO 2 R 4 , SO 3 R 4 , NR 4 R 5 , alkyl, aryl, aryl substituted with halogen, or heteroaryl; 
         each R 4  independently is H, alkyl, cycloalkyl, aryl, or heteroaryl; and 
         each R 5  independently is H, O-alkyl, O-aryl, alkyl, heteroaryl, or aryl. 
       
     
     
         2 . The compound of  claim 1  wherein p is 0. 
     
     
         3 . The compound of  claim 2  wherein A 1  is C 1-12  alkyl, optionally substituted with CO 2 CH 2 CH 3 . 
     
     
         4 . The compound of  claim 1  wherein p is 1. 
     
     
         5 . The compound of  claim 4  wherein A 1  is
 pyridinyl, optionally substituted with one or more halogen; or   phenyl, optionally substituted with one or more C 1-6  alkyl.   
     
     
         6 . The compound of  claim 1  wherein Y 1  is C(O). 
     
     
         7 . The compound of  claim 1  wherein Y 2  is a C(O). 
     
     
         8 . The compound of  claim 1  wherein R 1  is H. 
     
     
         9 . The compound of  claim 1  wherein R 2  is H. 
     
     
         10 . The compound of  claim 1  wherein p is 1 and R is H. 
     
     
         11 . A compound selected from: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or physiologically acceptable derivative thereof. 
       
     
     
         12 . A method for inhibiting the production of a virulence factor comprising contact with a compound of  claim 1 . 
     
     
         13 . A method for inhibiting the production of a virulence factor comprising contact with a compound of  claim 11 . 
     
     
         14 . The method of  claim 12  for the treatment or prevention of bacterial damage or disease. 
     
     
         15 . The method of  claim 13  for the treatment or prevention of bacterial damage or disease. 
     
     
         16 . The method of  claim 14  wherein the bacteria is  Pseudomonas aeruginosa  or  Burkholderia cepacia.    
     
     
         17 . The method of  claim 15  wherein the bacteria is  Pseudomonas aeruginosa  or  Burkholderia cepacia.    
     
     
         18 . A composition for inhibiting biofilm formation comprising a compound of  claim 1 . 
     
     
         19 . A composition for inhibiting biofilm formation comprising a compound of  claim 11 .