# US 11,111,216 B2 · Polycationic amphiphiles as antimicrobial agents and methods using same

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- Number: US 11,111,216 B2
- Document ID: US11111216B2
- Status: Granted
- Kind: B2
- Application number: 16/343,418
- Filed: 2017-10-26
- Published: 2020-09-03
- Granted: 2021-09-07
- Earliest claimed: 2016-10-26
- Assignees: Temple University of the Commonwealth System of Higher Education; Villanova University
- Applicants: Temple University-Of The Commonwealth System of Higher Education; Villanova University
- Inventors: William M. Wuest; Kevin P. C. Minbiole
- Web page: https://patentgrep.com/patent/US11111216B2

## CPC

- C07D 213/90: having more than three double bonds between ring members or between ring members and non-ring members
- A01N 33/12: Quaternary ammonium compounds
- A01N 43/40: six-membered rings
- C07C 211/63: having quaternised nitrogen atoms bound to acyclic carbon atoms
- C07D 213/06: containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
- C07D 213/36: Radicals substituted by singly-bound nitrogen atoms (nitro radicals C07D213/26)
- C07D 401/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 401/14: containing three or more hetero rings
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A01N: PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF (preservation of food or foodstuff A23); BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES (preparations for medical, dental or toiletry purposes which kill or prevent the growth or proliferation of unwanted organisms A61K); PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## 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.

## Claims

### Claim 1

A compound selected from the group consisting of formula I-IV:
wherein in formula I-III:
R1, R2, and R3 are each independently selected from the group consisting of H or C1-C25 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′, —CF3, —OCF3, 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 Ra, Rb, Rc, Rd, and Re is independently selected from the group consisting of H, C1-C6 alkyl, —OR′, —CN, —NO2, —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′, —CF3, —OCF3, and halogen;
each occurrence of R′ is independently selected from the group consisting of H and C1-4 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:
R1 and R2 are each independently selected from the group consisting of H or C1-C25 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′, —CF3, —OCF3, 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 R1 and R2 are C12 alkyl;
each occurrence of Ra and Rb is independently selected from the group consisting of C1-C6 alkyl, —OR′, —CN, —NO2, —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′, —CF3, —OCF3, and halogen; when each occurrence of Rc, Rd, and Re is independently selected from the group consisting of H, C1-C6 alkyl, —OR′, —CN, —NO2, —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′, —CF3, —OCF3, and halogen; or
each occurrence of Ra and Rb is independently selected from the group consisting of H, C1-C6 alkyl, —OR′, —CN, —NO2, —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′, —CF3, —OCF3, and halogen; when each occurrence of Rc, Rd, and Re is independently selected from the group consisting of C1-C6 alkyl, —OR′, —CN, —NO2, —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′, —CF3, —OCF3, and halogen;
each occurrence of R′ is independently selected from the group consisting of H and C1-4 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.

### Claim 2 (depends on 1)

The compound of claim 1, wherein in formula I-III at least one of R1, R2, and R3 is selected from the group consisting of C8 alkyl, C10 alkyl, C11 alkyl, C12 alkyl, C13 alkyl, C14 alkyl, C16 alkyl, and C18 alkyl; and
wherein in formula IV at least one of R1 and R2 is selected from the group consisting of C8 alkyl, C10 alkyl, C11 alkyl, C13 alkyl, C14 alkyl, C16 alkyl, and C18 alkyl.

### Claim 3 (depends on 1)

The compound of claim 1, wherein the R1, R2, and R3 are each independently selected from the group consisting of —R4—O—C(O)—R5 and —R4—(O)C—O—R5, wherein R4 and R5 are each independently an optionally substituted alkyl chain, provided that the total number of carbon atoms in the alkyl chains of R4 and R5 is 4 to 25 carbon atoms.

### Claim 4 (depends on 1)

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

### Claim 5 (depends on 1)

The compound of claim 1, wherein in formula I-III: R1, R2, and R3 are each C8-C18 alkyl; and wherein in formula IV: R1 and R2 are each C8-C11 or C13-C18 alkyl.

### Claim 6 (depends on 1)

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−.

### Claim 7 (depends on 1)

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.

### Claim 8

A compound selected from the group consisting of formula I-IV:
wherein in formula I-III:
R1, R2, and R3 are each independently selected from the group consisting of H or C1-C25 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′, —CF3, —OCF3, 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 Ra, Rb, Rc, Rd, and Re is independently selected from the group consisting of H, C1-C6 alkyl, —OR′, —CN, —NO2, —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′, —CF3, —OCF3, and halogen;
each occurrence of R′ is independently selected from the group consisting of H and C1-4 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:
R1 and R2 are each independently selected from the group consisting of —R4—O—C(O)—R5 and —R4—(O)C—O—R5, wherein R4 and R5 are each independently an optionally substituted alkyl chain, provided that the total number of carbon atoms in the alkyl chains of R4 and R5 is 4 to 25 carbon atoms;
each occurrence of Ra and Rb is independently selected from the group consisting of C1-C6 alkyl, —OR′, —CN, —NO2, —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′, —CF3, —OCF3, and halogen; when each occurrence of Rc, Rd, and Re is independently selected from the group consisting of H, C1-C6 alkyl, —OR′, —CN, —NO2, —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′, —CF3, —OCF3, and halogen; or
each occurrence of Ra and Rb is independently selected from the group consisting of H, C1-C6 alkyl, —OR′, —CN, —NO2, —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′, —CF3, —OCF3, and halogen; when each occurrence of Rc, Rd, and Re is independently selected from the group consisting of C1-C6 alkyl, —OR′, —CN, —NO2, —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′, —CF3, —OCF3, and halogen; and
each occurrence of R′ is independently selected from the group consisting of H and C1-4 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.