Modulation of pathogenicity
The present invention relates to the use of compounds of the general Formula (1): wherein in Formula (1), 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 furanyl, 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 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 alkyl, aryl, or heteroaryl, each 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 C 1-6 alkyl, which is optionally substituted with one or more R 3 .
29 . The compound of claim 28 wherein A 2 is hexyl.
30 . The compound of claim 28 wherein A 2 is ethyl substituted with cyclopentyl.
31 . The compound of claim 27 wherein A 1 is
wherein a is 0, 1, or 2.
32 . The compound of claim 30 wherein a is 0.
33 . The compound of claim 27 wherein Y 1 is C(O).
34 . The compound of claim 27 wherein Y 2 is C(O).
35 . The compound of claim 27 wherein R 1 is H.
36 . The compound of claim 27 wherein R 2 is H.
37 . A compound selected from:
or a pharmaceutically acceptable salt or physiologically acceptable derivative thereof.
38 . A method for inhibiting the production of a virulence factor comprising contact with a compound of claim 27 .
39 . A method for inhibiting the production of a virulence factor comprising contact with a compound of claim 37 .
40 . The method of claim 38 for the treatment or prevention of bacterial damage or disease.
41 . The method of claim 39 for the treatment or prevention of bacterial damage or disease.
42 . The method of claim 40 wherein the bacteria is Pseudomonas aeruginosa or Burkholderia cepacia.
43 . The method of claim 41 wherein the bacteria is Pseudomonas aeruginosa or Burkholderia cepacia.
44 . A composition for inhibiting biofilm formation comprising a compound of claim 27 .
45 . A composition for inhibiting biofilm formation comprising a compound of claim 37 .