Hinokitiol analogues, methods of preparing and pharmaceutical compositions thereof

Patent metadata

Field	Value
Publication number	US-12084411-B2
Application number	US-201917046608-A
Country	US
Kind code	B2
Filing date	Apr 12, 2019
Priority date	Apr 13, 2018
Publication date	Sep 10, 2024
Grant date	Sep 10, 2024

Abstract

Disclosed are analogues of hinokitiol, methods for preparing them, and pharmaceutical compositions thereof. Also disclosed are methods for their use in treating iron-related diseases.

First claim

We claim:

1. A compound having a structure according to Formula (I):

or a salt thereof; wherein
R a is selected from the group consisting of

Rb is hydrogen or methyl;
provided that if R a is

then R b is methyl.

2. The compound of claim 1 , wherein R a is selected from the group consisting of:

3. The compound of claim 1 , wherein R a is selected from the group consisting of:

4. The compound of claim 1 , wherein R a is selected from the group consisting of:

5. A compound selected from:

or a salt thereof.

6. The compound of claim 5 , wherein the compound is selected from:

or a salt thereof.

7. The compound of claim 5 , wherein the compound is selected from:

or a salt thereof.

8. The compound of claim 5 , wherein the compound is selected from:

or a salt thereof.

9. The compound of claim 5 , wherein the compound is selected from:

or a salt thereof.

10. The compound of claim 5 , wherein the compound is selected from:

or a salt thereof.

11. A compound selected from the group consisting of:

and salts thereof;

and salts thereof; and

and salts thereof.

12. The compound of claim 11 , selected from the group consisting of:

and salts thereof.

13. The compound of claim 11 , selected from the group consisting of:

and salts thereof.

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

15. A method of treating a disease or condition characterized by a deficiency of or a defect in an iron transporter, comprising administering to a subject in need thereof a therapeutically effective amount of a compound selected from the group consisting of tropolone and a compound of claim 1 .

16. The method of claim 15 , wherein the disease or condition characterized by a deficiency of or defect in an iron transporter is hypochromic, microcytic anemia.

17. A method of increasing (a) transepithelial iron transport, (b) physiology, (c) hemoglobinization, or (d) iron release, comprising administering to a subject in need thereof an effective amount of a compound selected from the group consisting of tropolone and a compound of claim 1 .

18. The method of claim 15 , further comprising administering an effective amount of one or more additional compounds selected from the group consisting of amphotericin B (AmB), calcimycin, nonactin, deferiprone, purpurogallin, and maltol.

19. The compound of claim 1 , wherein R b is hydrogen.

20. The compound of claim 1 , wherein R b is methyl.

21. The compound of claim 1 , provided that if R a is

then R b is methyl.

22. The compound of claim 1 , wherein R a is selected from the group consisting of

23. The compound of claim 1 , wherein R a is

24. The compound of claim 7 , wherein the compound is:

Assignees

• Univ Illinois

Inventors

• Burke Martin D
• Grillo Anthony S
• Cioffi Alexander G
• Santamaria Anna
• Blair Daniel
• Blake Andrew

Classifications

• C07C61/22

  having a carboxyl group bound to a six-membered ring · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• C07C2601/14

  The ring being saturated · CPC title

• C07C2601/08

  the ring being saturated · CPC title

• C07C2601/04

  with a four-membered ring · CPC title