Pyrrolomycins and methods of using the same

Patent metadata

Field	Value
Publication number	US-10954192-B2
Application number	US-201916505843-A
Country	US
Kind code	B2
Filing date	Jul 9, 2019
Priority date	Jul 16, 2015
Publication date	Mar 23, 2021
Grant date	Mar 23, 2021

Abstract

Provided herein are pyrrolomycin derivatives, which can be used to modulate Mcl-1, inhibit proliferation of bacteria and pathogens, as well as to treat infectious diseases and cancers.

First claim

What is claimed is:

1. A compound, or pharmaceutically acceptable salt thereof, having a structure selected from the group consisting of:

2. A pharmaceutical formulation comprising the compound or salt of claim 1 and a pharmaceutically acceptable excipient.

3. A method of inhibiting Mcl-1 in a cell, comprising contacting the cell with the compound or salt of claim 1 in an amount effective to inhibit Mcl-1 in the cell.

4. The method of claim 3 , wherein the cell is a cancerous cell.

5. A method of inhibiting the growth or proliferation of bacteria or a pathogen in a subject, comprising contacting the bacteria or pathogen with the compound or salt of claim 1 in an amount effective to inhibit the growth or proliferation of the bacteria or pathogen.

6. The method of claim 5 , wherein the bacteria are Gram-positive bacteria.

7. The method of claim 5 , wherein the bacteria are Gram-negative bacteria.

8. The method of claim 5 , wherein the pathogen or bacteria is Staphylococcus, Enterococcus, Bacillus, Streptococcus, Klebsiella, Acinetobacter, Pseudomonas, Enterobacter, Escherichia, Clostridium, Citrobacter, Serratia, Neisseria, Corynebacterium, Cyanobacterium, Salmonella, Shigella, Helicobacter, Brucella, Borrelia, Bordetella, Bartonella, Bacteroides, Burkholderia, Mycobacterium, Mycoplasma, Campylobacter, Chlamydia, Chlamydophila, Francisella, Haemophilus, Legionella, Leptospira, Listeria, Rickettsia, Vibrio, Ureaplasma, Yersinia, Treponema, Proteus, Stenotrophomonas, Plesiomonas, Nocardia, Actinomyces, Moraxella, Erysipelothrix, Actinobacillus, Anaplasma, Pasteurella, Alcaligenes, Achromobacter , or Candida.

9. The method of claim 5 , wherein the bacteria or pathogen is methicillin-resistant, carbapenem-resistant, fluoroquinone-resistant, vancomycin-resistant, or multidrug-resistant.

10. A method of killing a pathogen in a subject, comprising contacting the pathogen with the compound or salt of claim 1 in an amount effective to kill the pathogen.

11. A method of inhibiting the growth of biofilms, comprising contacting the biofilm with the compound or salt of claim 1 in an amount effective to inhibit the growth of biofilms.

12. The method of claim 11 , wherein the biofilm is due to a pathogen.

13. A method of treating infectious disease in a subject comprising administering to the subject a therapeutically effective amount of a compound or salt of claim 1 , wherein the infectious disease is caused by a bacteria or pathogen, and the bacteria or pathogen is Staphylococcus, Enterococcus, Bacillus, Streptococcus, Klebsiella, Acinetobacter, Pseudomonas, Enterobacter, Escherichia, Clostridium, Citrobacter, Serratia, Neisseria, Corynebacterium, Cyanobacterium, Salmonella, Shigella, Helicobacter, Brucella, Borrelia, Bordetella, Bartonella, Bacteroides, Burkholderia, Mycobacterium, Mycoplasma, Campylobacter, Chlamydia, Chlamydophila, Francisella, Haemophilus, Legionella, Leptospira, Listeria, Rickettsia, Vibrio, Ureaplasma, Yersinia, Treponema, Proteus, Stenotrophomonas, Plesiomonas, Nocardia, Actinomyces, Moraxella, Erysipelothrix, Actinobacillus, Anaplasma, Pasteurella, Alcaligenes, Achromobacter , or Candida , or a combination thereof.

14. The method of claim 13 , wherein the bacteria or pathogen is staphylococcus.

15. The method of claim 14 , wherein the bacteria or pathogen is Staphylococcus aureus.

16. The method of claim 13 , wherein the bacteria or pathogen is bacillus.

17. The method of claim 16 , wherein the bacteria or pathogen is Bacillus anthracis.

Assignees

• Univ Nebraska

Inventors

• Bayles Kenneth
• Li Rongshi
• Liu Yan

Classifications

• A61P31/04

  Antibacterial agents · CPC title

• C07D207/34 Primary

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms · CPC title

• C07D207/333

  Radicals substituted by oxygen or sulfur atoms · CPC title

• C07D231/16

  Halogen atoms or nitro radicals · CPC title

• C07D233/90

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title