Methods of use for compositions comprising a biocidal polyamine

Abstract

Compounds, compositions, and methods comprising a polyamine compound are described, which may be used to kill, disperse, treat, reduce biofilms, and/or inhibit or substantially prevent biofilm formation. In certain aspects, the present invention relates to compounds, compositions, and methods comprising polyamine compounds that have antimicrobial or dispersing activity against a variety of bacterial strains capable of forming biofilms.

1 . A method for dispersing or killing a biofilm, the method comprising a step of treating the biofilm with an anti-biofilm composition, thereby effectively dispersing or killing the biofilm;
 wherein the anti-biofilm composition comprises a biocidal polyamine compound selected from the group consisting of:   
       
         
           
           
               
               
           
         
       
       and a salt thereof; 
       wherein:
 each R a  is a member independently selected from the group consisting of 
 
       
         
           
           
               
               
           
         
         A 1 , A 2 , A 3 , A 4 , A 5 , A 6 , A 7 , A 8 , and A 9  are each an A n  member independently selected selected from the group consisting of N, CR a , and CR 5 ; or, alternatively, a pair of adjacent A n  members join to form a cycloalkyl, aryl, heterocyclyl, or heterocycloaryl ring; wherein at least one A i  member and at most five A n  members are an independently selected CR a ; 
         each R 1a , R 1b , R 1c , and R 1d  is a member independently selected from the group consisting of hydrogen, fluoro, alkyl, and fluoroalkyl; or, alternatively, an R 1a  and an R 1b  join to form an oxo group; 
         each R 2a , R 2b , R 2c , R 2d , R 2e , and R 2f  is a member independently selected from the group consisting of hydrogen, alkyl, fluoroalkyl, alkenyl, alkynyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl; alternatively, a pair of R 2  members from the same R a  group independently selected from the group R 2a  and R 2b , R 2c  and R 2d , and R 2e  and R 2f  join to form a member independently selected from the group consisting of spirocycloalkyl, spiroheterocycyl, and oxo; or, alternatively, an R 2a  and an R 2c  from the same R a  group join to form a ring independently selected from the group consisting of cycloalkyl and heterocycyl; 
         each R m  is a member independently selected from the group consisting of —CR 2a R 2b —, —CR 2c R 2d —, —C(R 2a )═(R 2b )—, —CC—, and —C(R 2a )(R 2b )-L 2 -C(R 2c )(R 2d )—; 
         each m is an integer independently selected from 1 to 20; 
         each L 1  and L 2  is a member independently selected from the group consisting of a bond, —O—, —C(O)O—, —NR 4 —, —NR 4 C(O)—, and —C(O)NR 4 —; 
         each R 3  is a member independently selected from the group consisting of —Z—R 4 , —Z—Y 1 —R 4 , —Z—Y 1 —Y 2 —R 4 , and —Z—Y 1 —Y 2 —Y 3 —R 4 ; 
         each R 4  is a member independently selected from the group consisting of hydrogen, alkyl, fluoroalkyl, alkenyl, alkynyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl; or, alternatively, for a —N(R 4 ) 2  group, one of the two R 4  in the group is a member selected from the group consisting of —(CO)OR 6a —, (CO)N(R 6a )(R 6b ), and —C(NR 6a )N(R 6b )(R 6c ); 
         each R 5  is a member independently selected from the group consisting of hydrogen, alkyl, hydroxyl, alkoxy, alkylamino, alkenyl, alkynyl, aryl, aryloxy, arylamino, cycloalkyl, cycloalkoxy, cycloalkylamino, heterocyclyl, heterocycyloxy, heterocycylamino, halo, haloalkyl, fluoroalkyloxy, heteroaryl, heteroaryloxy, heteroarylamino, arylalkyl, arylalkyloxy, arylalkylamino, heteroarylalkyl, heteroarylalkyloxy, heteroarylalkylamino; hydroxyalkyl, aminoalkyl, and alkylaminoalkyl; 
         each Y 1 , Y 2 , and Y 3  is an independently selected group of Formula IA: 
       
       
         
           
           
               
               
           
         
         each Z 1  and Z 2  is a member independently selected from the group consisting of NR 4  and O; and 
         each R 6a , R 6b , and R 6c  is a member independently selected from the group consisting of hydrogen, alkyl, fluoroalkyl, alkenyl, alkynyl, aryl, heteroaryl, arylalkyl, cycloalkyl, and heteroarylalkyl; or, alternatively, two R 6n  members R 6a  and R 6b  or R 6a  and R 6c  form a heterocycyl ring; 
         wherein the biocidal polyamine compound comprises at least two primary or secondary amino groups. 
       
     
     
         2 . The method of  claim 1 , wherein:
 each R a  is independently a group of Formula II:   
       
         
           
           
               
               
           
         
         each of the A n  members is independently selected from the group consisting of CR a  and CR 5 ; or, alternatively, a pair of adjacent A n  members join to form a cycloalkyl, aryl, heterocyclyl, or heterocycloaryl ring; wherein at least one A n  member and at most three A n  members are independently selected CR a , 
         each R 1a , R 1b , R 1c , and R 1d  is a member independently selected from the group consisting of hydrogen, fluoro, alkyl, and fluoroalkyl; 
         for each R a  member, at most two R m  of the R a  member are selected from the group consisting of —C(R 2a )═(R 2b )—, —CC—, and —C(R 2a )(R 2b )-L 2 -C(R 2c )(R 2d )—; and 
         each m is an integer independently selected from 1 to 16. 
       
     
     
         3 . The method of  claim 1 , wherein the biocidal polyamine compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
       and a salt thereof;
 wherein: 
 at least one A n  member and at most three A n  members are independently selected CR a , 
 each R 2a , R 2b , R 2c , R 2d , R 2e , and R 2f  is a member independently selected from the group consisting of hydrogen, alkyl, fluoroalkyl, alkenyl, alkynyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl; alternatively, a pair of R 2n  members from the R a  group independently selected from the group R 2a  and R 2b , R 2c  and R 2d , and R 2e  and R 2f  join to form a ring independently selected from the group consisting of spirocycloalkyl and spiroheterocycyl; or, alternatively, the R 2a  and the R 2c  from the R a  group join to form a ring independently selected from the group consisting of cycloalkyl and heterocycyl; 
 each m is an integer independently selected from 1 to 12; 
 each R 3  is a member independently selected from the group consisting of —Z—Y 1 —R 4  and —Z—Y 1 —Y 2 —R 4 ; and 
 each Z 1  and Z 2  is an independently selected NR 4 . 
 
     
     
         4 . The method of  claim 1 , wherein:
 A 1 , A 2 , A 3 , A 4 , A 5 , A 6 , A 7 , A 8  and A 9  are each an A n  member independently selected selected from the group consisting of CR a , and CR 5 ; or, alternatively, a pair of adjacent A n  members join to form a cycloalkyl, aryl, heterocyclyl, or heterocycloaryl ring;   each R 2a , R 2b , R 2c , R 2d , R 2e , and R 2f  is a member independently selected from the group consisting of hydrogen, alkyl, fluoroalkyl, alkenyl, alkynyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl;   each m is an integer independently selected from 1 to 10;   each L 1  and L 2  is a member independently selected from the group consisting of a bond, —O—, and —NR 4 —;   each R 3  is a member independently selected from the group consisting of —Z—R 4 , —Z—Y 1 —R 4 , and —Z—Y 1 —Y 2 —R 4 ; and   each Z 1  and Z 2  is an independently selected NR 4 .   
     
     
         5 . The method of  claim 4 , wherein the biocidal polyamine compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
       and a salt thereof;
 wherein: 
 each R a  is independently a group of Formula V: 
 
       
         
           
           
               
               
           
         
         each of the A n  members is independently selected from the group consisting of CR a  and CR 5 ; or, alternatively, a pair of adjacent A n  members join to form a cycloalkyl, aryl, heterocyclyl, or heterocycloaryl ring; wherein at least one A n  member and at most three A n  members are independently selected CR a , 
         each R 1a , R 1b , R 1c , and R 1d  is a member independently selected from the group consisting of hydrogen, fluoro, alkyl, and fluoroalkyl; 
         for each R a  member, at most two R m  of the R a  member are selected from the group consisting of —C(R 2a )═(R 2b )—, —CC—, and —C(R 2a )(R 2b )-L 2 -C(R 2c )(R 2d )—; and 
         each R 3  is a member independently selected from the group consisting of —Z—Y 1 —R 4  and —Z—Y 1 —Y 2 —R 4 . 
       
     
     
         6 . The method of  claim 1 , wherein the biocidal polyamine compound comprises at least four primary or secondary amino groups. 
     
     
         7 . The method of  claim 1 , wherein the biocidal polyamine compound comprises at least six primary or secondary amino groups 
     
     
         8 . The method of  claim 1 , wherein the biocidal polyamine compound is selected from the group consisting of 
       
         
           
           
               
               
           
         
       
       and a salt thereof;
 wherein each A n  member is an independently selected CR 5 . 
 
     
     
         9 . The method of  claim 8 , wherein the biocidal polyamine compound is selected from the group consisting of 
       
         
           
           
               
               
           
         
       
       and a salt thereof; and
 wherein R a  is an independently selected group of Formula VII: 
 
       
         
           
           
               
               
           
         
       
     
     
         10 . The method of  claim 8 , wherein R a  is —CH 2 [NH(CH 2 ) n ] p NH 2 ;
 wherein each n is an integer independently selected from 3 to 12; and 
 wherein each p is an integer independently selected from 1 to 3. 
 
     
     
         11 . (canceled) 
     
     
         12 . The method of  claim 8 , wherein the biocidal polyamine compound is selected from the group consisting of 
       
         
           
           
               
               
           
         
       
       and a salt thereof. 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . (canceled) 
     
     
         18 . (canceled) 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . (canceled) 
     
     
         22 . The method of  claim 1 , wherein the step of treating the biofilm with an anti-biofilm composition effectively disperses the biofilm. 
     
     
         23 . The method of  claim 1 , wherein the biofilm comprises an antibiotic-resistant bacterial species. 
     
     
         24 . The method of  claim 1 , wherein the method comprises a step of treating a contact lens with the anti-biofilm composition. 
     
     
         25 . The method of  claim 1 , wherein the method comprises a step of treating a pipe with the anti-biofilm composition. 
     
     
         26 . The method of  claim 1 , wherein the method comprises a step of treating a heating or cooling tower with the anti-biofilm composition. 
     
     
         27 . The method of  claim 1 , wherein the method comprises a step of coating an object with the anti-biofilm composition. 
     
     
         28 . The method of  claim 1 , wherein the anti-biofilm composition is a paint. 
     
     
         29 . The method of  claim 1 , wherein the method comprises a step of treating a patient with a biofilm-related disorder. 
     
     
         30 . A method for inhibiting formation of a biofilm, the method comprising a step of treating planktonic bacteria with an anti-biofilm composition of  claim 1 , thereby inhibiting incorporation of the planktonic bacteria into the biofilm.