Peptide antibiotics

Patent metadata

Field	Value
Publication number	US-11279733-B2
Application number	US-201816761067-A
Country	US
Kind code	B2
Filing date	Nov 2, 2018
Priority date	Nov 2, 2017
Publication date	Mar 22, 2022
Grant date	Mar 22, 2022

Abstract

There is provided a range of novel compounds. These novel compounds may demonstrate abroad spectrum antibacterial and antifungal activity. These compounds may be active against the emerging polymyxin resistant bacteria. These compounds may also be useful when used in conjunction with other pharmaceutically active agents.

First claim

The invention claimed is:

1. A compound of formula (I), or a salt or stereoisomer thereof:

wherein,
Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , Y 7 and Y 8 are independently selected from the group consisting of CH and N;
R 1 , R 3 , R 5 , R 6 , R 7 and R 8 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl and heteroaryl, each of which groups may be substituted or unsubstituted; wherein R 8 is not

wherein R 4 is selected from the group consisting of:

R 1 ′, R 2 ′, R 3 ′, R 4 ′, R 5 ′, R 6 ′, R 7 ′, R 8 ′ and R 9 ′ are independently selected from the group consisting of hydrogen and substituted or unsubstituted alkyl, or each pair of R 1 ′ and R 1 , R 3 ′ and R 3 , R 5 ′ and R 5 , R 6 ′ and R 6 , R 7 ′ and R 7 , and R 8 ′ and R 8 may be linked via an alkylene;
n is an integer selected from 0 or 1; and
Z is selected from

wherein
R 10 is selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl and heteroaryl, each of which groups may be substituted or unsubstituted; wherein Z does not comprise more than one (1) peptide linkage or bond, and
wherein Z does not have the structure

wherein R 11 , R 11 ′, and R 13 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl and heteroaryl, each of which groups may be substituted or unsubstituted;
wherein, when R 4 is

then Z is not selected from
the group consisting of

and when R 4 is

then Z is not selected from the group consisting

2. The compound of claim 1 , wherein the compound is a compound of formula (Ib):

wherein,
Y 1 and Y 2 are independently selected from the group consisting of CH and N;
R 5 and R 8 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl and heteroaryl, each of which groups may be substituted or unsubstituted; wherein R 8 is not

R 1 is selected from the group consisting of:

R 3 is

R 6 is selected from the group consisting of:

R 7 is selected from the group consisting of:

n is 1; and
Z is selected from

wherein
R 10 is selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl and heteroaryl, each of which groups may be substituted or unsubstituted; wherein Z does not comprise more than one (1) peptide linkage or bond, and
wherein Z does not have the structure

wherein R 11 , R 11 ′, and R 13 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl and heteroaryl, each of which groups may be substituted or unsubstituted.

3. The compound of claim 1 , wherein the compound is a compound of formula (Ic):

wherein,
R 5 , R 6 , R 7 and R 8 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl and heteroaryl, each of which groups may be substituted or unsubstituted; wherein R 8 is not

and
Z is selected from

wherein
R 10 is selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl and heteroaryl, each of which groups may be substituted or unsubstituted; wherein Z does not comprise more than one (1) peptide linkage or bond, and
wherein Z does not have the structure

wherein R 11 , R 11 ′, and R 13 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl and heteroaryl, each of which groups may be substituted or unsubstituted.

4. The compound of claim 3 , wherein the compound is a compound of formula (Id):

wherein
R 6 , R 7 , and R 8 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl and heteroaryl, each of which groups may be substituted or unsubstituted; wherein R 8 is not

and
Z is selected from

wherein
R 10 is selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl and heteroaryl, each of which groups may be substituted or unsubstituted; wherein Z does not comprise more than one (1) peptide linkage or bond, and
wherein Z does not have the structure

wherein R 11 , R 11 ′, and R 13 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl and heteroaryl, each of which groups may be substituted or unsubstituted.

5. The compound of claim 1 , wherein the compound is a compound of formula (Ig):

wherein,
R 5 and R 8 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl and heteroaryl, each of which groups may be substituted or unsubstituted; wherein R 8

Assignees

• Univ Queensland

Inventors

• Cooper Matthew
• Blaskovich Mark
• Gallardo-Godoy Alejandra
• Hansford Karl
• Elliott Alysha
• Muldoon Craig
• Becker Bernd

Classifications

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title

• C07K7/62 Primary

  Polymyxins; Related peptides · CPC title

• C07K7/56

  the cyclisation not occurring through 2,4-diamino-butanoic acid · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61P31/04

  Antibacterial agents · CPC title