Modulation of pathogenicity
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 (XIII)
or a pharmaceutically acceptable salt or physiologically functional derivative thereof,
wherein
A 6 is pyrazolyl, which may be optionally substituted with one or more R 3 ;
m is 1;
R 12 is H, CH 3 , CH 2 CH 3 , OCH 3 , OCH 2 CH 3 , OH, or SH;
r is 1;
A 7 is C(O) or C(S);
A 8 is C(R 14 ) 2 ;
each R 14 independently is H, alkyl, alkoxy, OH, or SH;
A 9 is C(O) or C(S);
q is 0 or 1;
A 5 is alkyl or heteroaryl, each of which may be 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 5 is C 6 -C 8 alkyl.
29 . The compound of claim 27 wherein A 9 is C(O).
30 . The compound of claim 27 wherein A 8 is CH 2 .
31 . The compound of claim 27 wherein A 7 is C(O).
32 . The compound of claim 27 wherein R 12 is H.
33 . The compound of claim 27 wherein A 6 is
wherein a is 0, 1, or 2.
34 . The compound of claim 27 wherein A 1 is
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 .