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 - 26 . (canceled) 
     
     
         27 . A compound of Formula (I) 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or physiologically functional derivative thereof, wherein 
         A 1  is pyrazolyl, which may be optionally substituted with one or more R 3 ; 
         p is 0; 
         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 0; 
         A 2  is heteroaryl, 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. 
       
     
     
         28 . The compound of  claim 27  wherein A 2  is pyrazolyl, which is optionally substituted with one or more R 3 . 
     
     
         29 . The compound of  claim 28  wherein A 2  is pyrazolyl, which is N-substituted with alkyl. 
     
     
         30 . The compound of  claim 27  wherein A 1  is 
       
         
           
           
               
               
           
         
       
       wherein a is 0, 1, 2, or 3. 
     
     
         31 . The compound of  claim 30  wherein a is 2 or 3. 
     
     
         32 . The compound of  claim 31  wherein A 1  is 
       
         
           
           
               
               
           
         
       
     
     
         33 . The compound of  claim 27  wherein Y 1  is C(O). 
     
     
         34 . The compound of  claim 27  wherein R 1  is H. 
     
     
         35 . A compound selected from: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or physiologically acceptable derivative thereof. 
     
     
         36 . A method for inhibiting the production of a virulence factor comprising contact with a compound of  claim 27 . 
     
     
         37 . A method for inhibiting the production of a virulence factor comprising contact with a compound of  claim 35 . 
     
     
         38 . The method of  claim 36  for the treatment or prevention of bacterial damage or disease. 
     
     
         39 . The method of  claim 37  for the treatment or prevention of bacterial damage or disease. 
     
     
         40 . The method of  claim 38  wherein the bacteria is  Pseudomonas aeruginosa  or  Burkholderia cepacia.    
     
     
         41 . The method of  claim 39  wherein the bacteria is  Pseudomonas aeruginosa  or  Burkholderia cepacia.    
     
     
         42 . A composition for inhibiting biofilm formation comprising a compound of  claim 27 . 
     
     
         43 . A composition for inhibiting biofilm formation comprising a compound of  claim 35 .