US2008194607A1PendingUtilityA1

Modulation of pathogenicity

61
Assignee: AMMENDOLA ALDOPriority: Mar 8, 2002Filed: Dec 28, 2007Published: Aug 14, 2008
Est. expiryMar 8, 2022(expired)· nominal 20-yr term from priority
C07D 307/68C07D 231/16A61K 8/4986A61K 31/505C07D 409/12C07D 471/04C07D 333/70A61Q 17/005C07D 333/38C07D 403/12A61K 31/445A61K 31/415C07D 409/04A61P 31/04A01N 43/56A01N 43/54A61K 31/435A61K 8/4973C07D 231/40A61K 31/44A61K 31/38A61K 8/49A61Q 19/00A61K 31/175A61K 31/42Y02A50/30
61
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Claims

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;

Claims

exact text as granted — not AI-modified
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; 
 Y 1  is —C(O)—, —C(S)—, or a bond; 
 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)—; 
 A 2  is a diazolyl, 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 A 1  is pyrimidinyl, thienyl, benzothienyl, or C 1-10  alkyl, each of which may be optionally substituted with one or more R 3 . 
     
     
         3 . The compound of  claim 2  wherein each R 3  independently is halogen, C 1-6  alkyl, or C 1-6  haloalkyl. 
     
     
         4 . The compound of  claim 1  wherein Y 1  is C(O). 
     
     
         5 . The compound of  claim 1  wherein Y 1  is a bond. 
     
     
         6 . The compound of  claim 1  wherein R 1  is H. 
     
     
         7 . The compound of  claim 1  wherein R 2  is H. 
     
     
         8 . The compound of  claim 1  wherein A 2  is 
       
         
           
           
               
               
           
         
       
       where
 each a independently is 1, 2, or 3; and 
 each R 3  independently is C 1-6  alkyl, halogen, C 1-6  haloalkyl, aryl, or aryl substituted with halogen. 
 
     
     
         9 . The compound of  claim 8  wherein at least one R 3  is substituted from a nitrogen atom. 
     
     
         10 . A compound selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or physiologically acceptable derivative thereof. 
     
     
         11 . A method for inhibiting the production of a virulence factor comprising contact with a compound of  claim 1 . 
     
     
         12 . A method for inhibiting the production of a virulence factor comprising contact with a compound of  claim 10 . 
     
     
         13 . The method of  claim 11  for the treatment or prevention of bacterial damage or disease. 
     
     
         14 . The method of  claim 12  for the treatment or prevention of bacterial damage or disease. 
     
     
         15 . The method of  claim 13  wherein the bacteria is  Pseudomonas aeruginosa  or  Burkholderia cepacia.    
     
     
         16 . The method of  claim 14  wherein the bacteria is  Pseudomonas aeruginosa  or  Burkholderia cepacia.    
     
     
         17 . A composition for inhibiting biofilm formation comprising a compound of  claim 1 . 
     
     
         18 . A composition for inhibiting biofilm formation comprising a compound of  claim 10 .

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