Granted Patent B2

US 12,263,156 · App. 17/502,975 · Granted Apr 1, 2025

Inventors: Mario Rivera (Baton Rouge, LA); Huili Yao (Baton Rouge, LA); Richard A. Bunce (Stillwater, OK); Baskar Nammalwar (San Diego, CA); Krishna Kumar Gnanasekaran (Mississauga, CA); Kate Eshelman (Alexandria, VA); Achala N. D. Punchi Hewage (Lawrence, KS); Scott Lovell (Shawnee, KS); Anabel Soldano (Baton Rouge, LA)

Assignees: Board of Supervisors of Louisiana State University and Agricultural and Mechanical College; The Board of Regents for Oklahoma State University; University of Kansas

A61K31/4035A61P31/04

Abstract

Claims (42)

1. A method of inhibiting biofilm formation, treating bacteria within a biofilm, or remediating a biofilm in or on a subject, the method comprising administering to the subject an effective amount of a compound according to Formula I

or a pharmaceutically acceptable salt and/or a solvate thereof, wherein

R 1 is C 1 -C 6 alkoxy, H, OH, or halo;

R 2 and R 3 are each independently C 1 -C 6 alkoxy, H, or OH;

R 4 and R 5 are each independently H or halo;

X 1 is CH 2 or O; and

m is 0, 1, 2, 3, 4, or 5;

provided that:

at least one of R 1 , R 2 , and R 3 is OH or C 1 -C 6 alkoxy;

when X 1 is O, m is not 0; and

when R 2 is OH, R 1 , R 3 , R 4 , and R 5 are each independently H, and X 1 is CH 2 , then m is not 0; and

wherein the subject is suffering from or at risk of suffering from a bacterial infection.

2. The method of claim 1 , wherein the method comprises administering to the subject a pharmaceutical composition, wherein the pharmaceutical composition comprises a compound of Formula I and a pharmaceutically acceptable carrier.

3. The method of claim 2 , wherein the pharmaceutical composition is formulated for topical administration.

4. The method of claim 1 , the method further comprising administering an effective amount of fluoroquinolone antibiotic to the subject, administering an effective amount of aminoglycoside antibiotic to the subject, and/or administering an effective amount of polymyxin antibiotic to the subject.

5. The method of claim 1 , wherein the bacterial infection comprises a Gram-negative bacterial infection.

6. The method of claim 1 , wherein the bacterial infection comprises a Pseudomonas aeruginosa infection, an Acinetobacter baumannii infection, a Klebsiella pneumonia infection, a Yersinia pestis infection, a Shigella dysenteriae infection, an Enterobacter sp. infection, an Acinetobacter sp. infection, a Salmonella typhimurium infection, a Serratia sp. infection, or a combination of any two or more thereof.

7. The method of claim 1 , wherein

R 1 , R 2 , and R 3 are each independently H or OH;

R 4 and R 5 are each independently H or halo;

X 1 is CH 2 or O; and

m is 0, 1, 2, 3, 4, or 5;

provided that at least one of R 1 , R 2 , and R 3 is OH.

8. The method of claim 7 , wherein X 1 is CH 2 .

9. The method of claim 1 , wherein the compound is of Formula IA

or a pharmaceutically acceptable salt and/or a solvate thereof, wherein n is 1, 2, or 3;

provided that R 2 is not OH when n is 1 and R 1 , R 3 , R 4 , and R 5 are each independently H.

10. The method of claim 9 , wherein one of R 1 and R 3 is OH, one of R 1 and R 3 is H, and R 2 is H.

11. The method of claim 10 , wherein R 4 and R 5 are each independently H, bromine, chlorine, or fluorine.

12. The method of claim 11 , wherein R 4 and R 5 are each independently H or chlorine.

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

or a pharmaceutically acceptable salt and/or solvate thereof.

14. The method of claim 13 , wherein the compound is

or a pharmaceutically acceptable salt and/or solvate thereof.

15. The method of claim 13 , wherein the compound is

or a pharmaceutically acceptable salt and/or solvate thereof.

16. The method of claim 1 , wherein the method inhibits biofilm formation in or on the subject.

17. The method of claim 1 , wherein the method treats bacteria within a biofilm in or on the subject.

18. The method of claim 1 , wherein the method remediates a biofilm in or on the subject.

19. The method of claim 1 , wherein the subject is a human or a surface.

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

or a pharmaceutically acceptable salt thereof.

Assignments (2)

Continuity (3)

References Cited (146)