Polycationic amphiphiles as antimicrobial agents and methods using same

Patent metadata

Field	Value
Publication number	US-11111216-B2
Application number	US-201716343418-A
Country	US
Kind code	B2
Filing date	Oct 26, 2017
Priority date	Oct 26, 2016
Publication date	Sep 7, 2021
Grant date	Sep 7, 2021

Abstract

The present invention includes novel polycationic amphiphilic compounds useful as antimicrobial agents. The present invention further includes methods useful for removing microorganisms and/or biofilm-embedded microorganisms from a surface. The present invention further includes compositions and methods useful for preventing or reducing the growth or proliferation of microorganisms and/or biofilm-embedded microorganisms on a surface.

First claim

The invention claimed is:

1. A compound selected from the group consisting of formula I-IV:

wherein in formula I-III:
R 1 , R 2 , and R 3 are each independently selected from the group consisting of H or C 1 -C 25 alkyl, wherein the alkyl group may be optionally substituted with —OR′, —NR′ 2 , —NR′—C(O)R′, —C(O)NR′ 2 , —NR′—C(O)CR′═CR′, —SR′, —O—C(O)R′, —C(O)OR′, —C(O)R′, —CF 3 , —OCF 3 , halogen, benzyl, o-vinylbenzyl, m-vinylbenzyl, p-vinylbenzyl, phenyl, allyl, and substituted allyl, further wherein the alkyl group may optionally be interrupted with a —O—C(O)— group or a —C(O)O— group;
each occurrence of R a , R b , R c , R d , and R e is independently selected from the group consisting of H, C 1 -C 6 alkyl, —OR′, —CN, —NO 2 , —NR′ 2 , —N—C(O)R′, —C(O)NR′ 2 , —N—C(O)CR′═CR′, —SR′, —O—C(O)R′, —C(O)OR′, —C(O)R′, —CF 3 , —OCF 3 , and halogen;
each occurrence of R′ is independently selected from the group consisting of H and C 1-4 alkyl;
Y is N;
each occurrence of Z − is independently selected from the group consisting of Br − and I − ;
m is an integer from 0 to 4;
n is an integer from 0 to 4; and
p is an integer from 0 to 4; and
wherein in formula IV:
R 1 and R 2 are each independently selected from the group consisting of H or C 1 -C 25 alkyl, wherein the alkyl group may be optionally substituted with —OR′, —NR′ 2 , —NR′—C(O)R′, —C(O)NR′ 2 , —NR′—C(O)CR′═CR′, —SR′, —O—C(O)R′, —C(O)OR′, —C(O)R′, —CF 3 , —OCF 3 , halogen, benzyl, o-vinylbenzyl, m-vinylbenzyl, p-vinylbenzyl, phenyl, allyl, and substituted allyl, further wherein the alkyl group may optionally be interrupted with a —O—C(O)— group or a —C(O)O— group, and each occurrence of Z − is I − when R 1 and R 2 are C 12 alkyl;
each occurrence of R a and R b is independently selected from the group consisting of C 1 -C 6 alkyl, —OR′, —CN, —NO 2 , —NR′ 2 , —N—C(O)R′, —C(O)NR′ 2 , —N—C(O)CR′═CR′, —SR′, —O—C(O)R′, —C(O)OR′, —C(O)R′, —CF 3 , —OCF 3 , and halogen; when each occurrence of R c , R d , and R e is independently selected from the group consisting of H, C 1 -C 6 alkyl, —OR′, —CN, —NO 2 , —NR′ 2 , —N—C(O)R′, —C(O)NR′ 2 , —N—C(O)CR′═CR′, —SR′, —O—C(O)R′, —C(O)OR′, —C(O)R′, —CF 3 , —OCF 3 , and halogen; or
each occurrence of R a and R b is independently selected from the group consisting of H, C 1 -C 6 alkyl, —OR′, —CN, —NO 2 , —NR′ 2 , —N—C(O)R′, —C(O)NR′ 2 , —N—C(O)CR′═CR′, —SR′, —O—C(O)R′, —C(O)OR′, —C(O)R′, —CF 3 , —OCF 3 , and halogen; when each occurrence of R c , R d , and R e is independently selected from the group consisting of C 1 -C 6 alkyl, —OR′, —CN, —NO 2 , —NR′ 2 , —N—C(O)R′, —C(O)NR′ 2 , —N—C(O)CR′═CR′, —SR′, —O—C(O)R′, —C(O)OR′, —C(O)R′, —CF 3 , —OCF 3 , and halogen;
each occurrence of R′ is independently selected from the group consisting of H and C 1-4 alkyl;
each occurrence of Z − is independently selected from the group consisting of Br − and I − ;
m is an integer from 0 to 4; and
n is an integer from 0 to 4.

2. The compound of claim 1 , wherein in formula I-III at least one of R 1 , R 2 , and R 3 is selected from the group consisting of C 8 alkyl, C 10 alkyl, C 11 alkyl, C 12 alkyl, C 13 alkyl, C 14 alkyl, C 16 alkyl, and C 18 alkyl; and
wherein in formula IV at least one of R 1 and R 2 is selected from the group consisting of C 8 alkyl, C 10 alkyl, C 11 alkyl, C 13 alkyl, C 14 alkyl, C 16 alkyl, and C 18 alkyl.

3. The compound of claim 1 , wherein the R 1 , R 2 , and R 3 are each independently selected from the group consisting of —R 4 —O—C(O)—R 5 and —R 4 —(O)C—O—R 5 , wherein R 4 and R 5 are each independently an optionally substituted alkyl chain, provided that the total number of carbon atoms in the alkyl chains of R 4 and R 5 is 4 to 25 carbon atoms.

4. The compound of claim 1 , wherein Z − is Br − .

5. The compound of claim 1 , wherein in formula I-III: R 1 , R 2 , and R 3 are each C 8 -C 18 alkyl; and wherein in formula IV: R 1 and R 2 are each C 8 -C 11 or C 13 -C 18 alkyl.

6. The compound of claim 1 , wherein the compound is selected from the group consisting of:

wherein each occurrence of Z − is independently selected from the group consisting of I − and Br − .

7. The compound of claim 1 , wherein the at least one compound is bound to a second compound or moiety selected from the group consisting of a QAC, an antimicrobial peptide, a sugar, an iron siderophore, a solid surface, a poly(alkyl ether), and a nucleophilic residue.

8. A compound selected from the group consisting of formula I-IV:

wherein in formula I-III:
R 1 , R 2 , and R 3 are each independently selected from the group consisting of H or C 1 -C 25 alkyl, wherein the alkyl group may be optionally substituted with —OR′, —NR′ 2 , —NR′—C(O)R′, —C(O)NR′ 2 , —NR′—C(O)CR′═CR′, —SR′, —O—C(O)R′, —C(O)OR′, —C(O)R′, —CF 3 , —OCF 3 , halogen, benzyl, o-vinylbenzyl, m-vinylbenzyl, p-vinylbenzyl, phenyl, allyl, and substituted allyl, further wherein the alkyl group may optionally be interrupted with a —O—C(O)— group or a —C(O)O— group;
each occurrence of R a , R b , R c , R d , and R e is independently selected from the group consisting of H, C 1 -C 6 alkyl, —OR′, —CN, —NO 2 , —NR′ 2 , —N—C(O)R′, —C(O)NR′ 2 , —N—C(O)CR′═CR′, —SR′, —O—C(O)R′, —C(O)OR′, —C(O)R′, —CF 3 , —OCF 3 , and halogen;
each occurrence of R′ is independently selected from the group consisting of H and C 1-4 alkyl;
Y is N;
each occurrence of Z − is independently selected from the group consisting of Br − and I − ;
m is an integer from 0 to 4;
n is an integer from 0 to 4; and
p is an integer from 0 to 4; and
wherein in formula IV:
R 1 and R 2 are each independently selected from the group consisting of —R 4 —O—C(O)—R 5 and —R 4 —(O)C—O—R 5 , wherein R 4 and R 5 are each independently an optionally substituted alkyl chain, provided that the total number of carbon atoms in the alkyl chains of R 4 and R 5 is 4 to 25 carbon atoms;
each occurrence of R a and R b is independently selected from the group consisting of C 1 -C 6 alkyl, —OR′, —CN, —NO 2 , —NR′ 2 , —N—C(O)R′, —C(O)NR′ 2 , —N—C(O)CR′═CR′, —SR′, —O—C(O)R′, —C(O)OR′, —C(O)R′, —CF 3 , —OCF 3 , and halogen; when each occurrence of R c , R d , and R e is independently selected from the group consisting of H, C 1 -C 6 alkyl, —OR′, —CN, —NO 2 , —NR′ 2 , —N—C(O)R′, —C(O)NR′ 2 , —N—C(O)CR′═CR′, —SR′, —O—C(O)R′, —C(O)OR′, —C(O)R′, —CF 3 , —OCF 3 , and halogen; or
each occurrence of R a and R b is independently selected from the group consisting of H, C 1 -C 6 alkyl, —OR′, —CN, —NO 2 , —NR′ 2 , —N—C(O)R′, —C(O)NR′ 2 , —N—C(O)CR′═CR′, —SR′, —O—C(O)R′, —C(O)OR′, —C(O)R′, —CF 3 , —OCF 3 , and halogen; when each occurrence of R c , R d , and R e is independently selected from the group consisting of C 1 -C 6 alkyl, —OR′, —CN, —NO 2 , —NR′ 2 , —N—C(O)R′, —C(O)NR′2, —N—C(O)CR′═CR′, —SR′, —O—C(O)R′, —C(O)OR′, —C(O)R′, —CF 3 , —OCF 3 , and halogen; and
each occurrence of R′ is independently selected from the group consisting of H and C 1-4 alkyl;
each occurrence of Z − is independently selected from the group consisting of Br − and I − ;
m is an integer from 0 to 4; and
n is an integer from 0 to 4.

Assignees

• Univ Temple
• Univ Villanova

Inventors

• Wuest William M
• Minbiole Kevin P C

Classifications

• C07D213/90 Primary

  having more than three double bonds between ring members or between ring members and non-ring members · CPC title

• A01N43/40 Primary

  six-membered rings · CPC title

• A01N33/12

  Quaternary ammonium compounds · CPC title

• C07D401/14

  containing three or more hetero rings · CPC title

• C07D401/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title