Ethoxyphenyl thienyl compounds and methods for the treatment of bacterial infections

Patent metadata

Field	Value
Publication number	US-9688653-B2
Application number	US-201414514725-A
Country	US
Kind code	B2
Filing date	Oct 15, 2014
Priority date	Jun 14, 2013
Publication date	Jun 27, 2017
Grant date	Jun 27, 2017

Abstract

This invention relates generally to the discovery of a method of inhibiting, preventing or treating bacterial infections. The invention also relates to a method of inhibiting bacterial capsule biogenesis.

First claim

What is claimed is:

1. A method of inhibiting capsule biogenesis in a bacterium which comprises administering to the bacterium an effective amount of a composition comprising

wherein R 1 is C 1-8 alkyl, C 1-8 alkoxy, C 1-8 haloalkoxy;
R 2 is hydrogen; and
R 3 is substituted aryl or substituted furan group.

2. The method of claim 1 , wherein the capsule biogenesis is K1 or K5 capsule biogenesis.

3. The method of claim 1 , wherein the bacterium is a gram-negative bacteria.

4. The method of claim 3 , wherein the gram-negative bacteria is Campylobacter jejuni, Enterobacter cloacae, Escherichia Coli, Haemophilus influenzae, Klebsiella pneumoniae, Legionella pneumophila , Methicillin-resistant Staphylococcus aureus (MRSA), Neisseria meningitides, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella typhimurium, Serratia marcescens, Staphylococcus aureus or a combination thereof.

5. A method of treating a subject suffering from a bacterial infection comprising administering a therapeutically effective amount of a composition comprising

wherein R 1 is C 1-8 alkyl, C 1-8 alkoxy, C 1-8 haloalkoxy;
R 2 is hydrogen; and
R 3 is substituted furan group.

6. The method of claim 5 , wherein the bacterium is a gram-negative bacteria.

7. The method of claim 6 , wherein the gram-negative bacteria is Campylobacter jejuni, Enterobacter cloacae, Escherichia Coli, Haemophilus influenzae, Klebsiella pneumoniae, Legionella pneumophila , Methicillin-resistant Staphylococcus aureus (MRSA), Neisseria meningitides, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella typhimurium, Serratia marcescens, Staphylococcus aureus or a combination thereof.

8. The method of claim 5 , further comprising administering an agent that targets a bacterial cell wall.

9. The method of claim 8 , wherein the agent is a penicillin or a cephalosporin.

10. The method of claim 5 , wherein the bacterial infection is a urinary tract infection (UTI), or a disseminated staphylococcus infection.

11. The method of claim 10 , wherein the bacterial infection is a urinary tract infection (UTI).

12. The method of claim 11 wherein the urinary tract infection (UTI) is a bladder infection.

13. The method of claim 11 wherein the urinary tract infection (UTI) is a kidney infection.

14. The method of claim 5 , wherein the subject is a mammal.

15. The method of claim 14 , wherein the mammal is a human.

16. The method of claim 1 , wherein R 1 is a fluoro alkoxy group.

17. The method of claim 1 , wherein R 1 is a methoxy, ethoxy, propoxy, or butoxy group.

18. The method of claim 1 , wherein R 3 is a substituted aryl group with one or more fluoro substituents.

19. The method of claim 1 , wherein R 3 is a bromo substituted furan group.

Assignees

• Univ Duke
• Univ Kansas
• Southern Res Inst
• Univ Kansas

Inventors

• Seed Patrick C
• Goller Carlos C
• Rogers Steven
• Maki Brooks
• Schoenen Frank
• Noah James
• White E Lucile

Classifications

• A61K31/545

  Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula: [IMAGE cpc-sch-A61K-0953.gif] , e.g. cephalosporins, {cefaclor, or cephalexine} · CPC title

• A61K31/43

  Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula [IMAGE cpc-sch-A61K-0952.gif], e.g. penicillins, penems · CPC title

• A61K31/4439

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title

• A61K31/381

  having five-membered rings · CPC title

• C12Q1/025

  for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics (antimicrobial activity C12Q1/18) · CPC title