Chrysophaentin analogs and use thereof

Patent metadata

Field	Value
Publication number	US-12398115-B2
Application number	US-202017602133-A
Country	US
Kind code	B2
Filing date	Apr 9, 2020
Priority date	Apr 9, 2019
Publication date	Aug 26, 2025
Grant date	Aug 26, 2025

Abstract

Provided are 9-dechlorochrysophaentin analog compounds and the synthesis process thereof. The disclosed compound have remarkable antimicrobial activities that are comparable to, or even more potent than, the natural product chrysophaentin A. Also provided are method of inhibiting bacterial growth or treating bacterial infection by administering an effective amount of the disclosed compounds.

First claim

What is claimed is:

1. A compound of formula (I), or a pharmaceutically acceptable salt thereof,

wherein
R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are independently H, C 1-4 alkyl, C 3-6 cycloalkyl, —CH 2 C 3-6 cyclalkyl, —C(O)H, —C(O)C 1-4 alkyl, —C(O)C 3-6 cycloalkyl, or —C(O)CH 2 C 3-6 cyclalkyl; and
Y is halogen and Z is H; or Y is H and Z is halogen.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, having a structure of formula (I-a).

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Y is halogen and Z is H.

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Y is H and Z is halogen.

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are independently H or C 1-4 alkyl.

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are independently H, methyl, or isopropyl.

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , and R 3 are H; and R 4 , R 5 , and R 6 are independently H, methyl, or isopropyl.

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 and R 4 are H; and R 5 and R 6 are independently H, methyl, or isopropyl.

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein
R 1 , R 2 , R 3 R 4 , R 5 , and R 6 are H, Y is halogen, Z is H;
R 1 , R 2 , R 3 R 4 , R 5 , and R 6 are H, Y is H, Z is halogen;
R 1 , R 2 , R 3 and R 4 are H; R 5 and R 6 are methyl, Y is halogen, Z is H; or
R 1 , R 2 , R 3 and R 4 are H; R 5 and R 6 are methyl, Y is H, Z is halogen.

10. The compound of claim 9 , or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 R 4 , R 5 , and R 6 are H, Y is Cl, and Z is H.

11. The compound of claim 9 , or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 R 4 , R 5 , and R 6 are H, Y is H, and Z is Cl.

12. The compound of claim 9 , or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 and R 4 are H; R 5 and R 6 are methyl, Y is Cl, and Z is H.

13. The compound of claim 9 , or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 and R 4 are H; R 5 and R 6 are methyl, Y is H, and Z is Cl.

14. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

15. A method of inhibiting the growth of a bacterium, comprising contacting the bacterium with an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

16. The method of claim 15 , wherein the bacterium is a Gram-positive bacterium or a Gram-negative bacterium.

17. The method of claim 15 , wherein the bacterium is S. aureus or E. faecium.

18. The method of claim 15 , wherein the bacterium is an antibiotic-resistant bacterium.

19. The method of claim 15 , wherein the bacterium is methicillin resistant S. aureus (MRSA) or vancomycin resistant E. faecium (VREF).

20. A method of treating a bacterial infection in a subject in need thereof, comprising administering to the subject an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

Assignees

• Univ Vanderbilt

Inventors

• Sulikowski Gary A
• Fullenkamp Christopher
• Kim Kwangho
• Jana Somnath

Classifications

• A61P31/04

  Antibacterial agents · CPC title

• C07C2601/00

  Systems containing only non-condensed rings · CPC title

• C07D321/00 Primary

  Heterocyclic compounds containing rings having two oxygen atoms as the only ring hetero atoms, not provided for by groups C07D317/00 - C07D319/00 · CPC title

• C07C43/29 Primary

  containing halogen · CPC title