4-oxazolidinone antimicrobial agents

• US 10,844,025 B2
• Filed: 08/22/2017
• Issued: 11/24/2020
• Est. Priority Date: 08/22/2016
• Status: Active Grant

• Current Assignee: North Carolina State University (University of North Carolina System)
• Original Assignee: North Carolina State University (University of North Carolina System)
• Inventors: Pierce, Joshua G., Mills, Jonathan J.
• Primary Examiner(s): Davis, Brian J
• Application Number:
  US16/327,478
• Publication Number:
  US 20190177285A1
• Time in Patent Office: 1,190 Days
• Field of Search: None
• CPC Class Codes: A01N 43/76 1,3-Oxazoles; Hydrogenated 1,3-oxazoles
• CPC Class Codes: A61L 2300/204 with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/08 Materials for coatings
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: C07D 263/40 attached in position 4
• CPC Class Codes: C07D 263/46 Sulfur atoms

Abstract

Provided herein are oxazolidinone derivatives that can exhibit anti-microbial activity and/or activity as biofilm modulating agents (e.g., activity as biofilm inhibitors and/or activity as biofilm dispersal agents). The compounds can exhibit potent activity anti-microbial activity (e.g., potent activity against Gram-positive positive bacteria including methicillin-resistant Staphylococcus aureus). The compounds can exhibit potent activity against biofilms. In some cases, the compounds can exhibit both anti-microbial activity and biofilm modulation properties.

Claims

1. A compound defined by Formula I

2. The compound of claim 1, wherein R¹ is a C₁-C₄ alkyl group.

3. The compound of claim 2, wherein R¹ is a branched C₃-C₄ alkyl group.

4. The compound of claim 3, wherein R¹ is an isopropyl group.

5. The compound of claim 1, wherein R¹ is an aryl group or an alkylaryl group.

6. The compound of claim 1, wherein R³ is hydrogen.

7. The compound of claim 1, wherein R³ is chosen from alkyl, aryl, and alkylaryl, each optionally substituted with one or more substituents individually chosen from R⁵.

8. The compound of claim 7, wherein R³ is an aryl group optionally substituted with one or more substituents individually chosen from R⁵.

9. The compound of claim 1, wherein R² is chosen from alkyl, aryl, and alkylaryl, each optionally substituted with one or more substituents individually chosen from R⁵.

10. The compound of claim 1, wherein X is O.

11. The compound of claim 1, wherein R⁴ is hydrogen.

12. The compound of claim 1, wherein R⁴ is chosen from alkyl, aryl, and alkylaryl.

13. The compound of claim 12, wherein R⁴ comprises a C₁-C₄ alkyl group or a phenyl group.

14. The compound of claim 1, wherein the compound is defined by Formula II

15. The compound of claim 14, wherein R⁶ comprises a C₁-C₈ alkyl group.

16. The compound of claim 1, wherein the compound is defined by Formula III

17. A biofilm preventing, removing, or inhibiting composition comprising a carrier and an effective amount of a compound defined by claim 1.

18. A method of treating a subject infected with a bacterium comprising administering to the subject a therapeutically effective amount of a compound of claim 1.

19. A method of controlling biofilm formation on a substrate comprising contacting the substrate with a compound defined by claim 1 in an amount effective to inhibit biofilm formation.

20. A medical device comprising:

(a) a medical device substrate; and

(b) an effective amount of a compound of claim 1, either coating the substrate, or incorporated into the substrate, wherein said effective amount of said compound prevents or inhibits the growth of a biofilm thereon.