SMALL MOLECULE FERROPTOSIS INDUCERS

• US 20190315681A1
• Filed: 06/18/2019
• Published: 10/17/2019
• Est. Priority Date: 12/19/2016
• Status: Active Grant

• Current Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Original Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Inventors: Stockwell, Brent R., Shimada, Kenichi, Skouta, Rachid
• Granted Patent: US 10,947,188 B2
• Time in Patent Office: Days
• CPC Class Codes: C07C 2601/14 The ring being saturated
• CPC Class Codes: C07C 2603/18 Fluorenes; Hydrogenated fluorenes
• CPC Class Codes: C07C 311/15 Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
• CPC Class Codes: C07C 311/20 having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
• CPC Class Codes: C07C 311/21 having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07D 295/26 Sulfur atoms
• CPC Class Codes: C07D 309/14 Nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 407/12 linked by a chain containing hetero atoms as chain links

Abstract

The present invention provides, inter alia, a compound according to formula (I):

Also provided are compositions containing a pharmaceutically acceptable carrier and a compound according to the present invention. Further provided are methods for regulating GPX4 in a cell and methods for inducing ferroptosis in a cell.

Claims

1. A compound according to formula (I):

2. A compound according to claim 1 having the structure of formula (II):

3. A compound according to claim 1, which is selected from the group consisting of:

4. A compound according to claim 1, wherein the compound is FIN56:

5. A composition comprising a compound according to any one of claims 1-4, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

6. A pharmaceutically acceptable salt of a compound according to any one of claims 1-4.

7. A composition comprising a pharmaceutically acceptable salt of a compound according to any one of claims 1-4 and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

8. A method for inducing ferroptosis in a cell comprising contacting the cell with an effective amount of a compound having the structure of formula (I):

9. The method according to claim 8, wherein the compound has the structure of formula (II):

10. The method according to claim 8, wherein the compound is selected from the group consisting of:

11. The method according to claim 8, wherein the compound is FIN56:

12. The method according to claim 8, wherein the cell is mammalian.

13. The method according to claim 12, wherein the cell is human.

14. The method according to claim 8, wherein the cell is from a laboratory animal.

15. The method according to claim 8, which is carried out in vitro, in vivo, or ex vivo.

16. A method for decreasing GPX4 in a cell, comprising contacting the cell with an effective amount of a compound having the structure of formula (I):

17. The method according to claim 16, wherein the compound has the structure of formula (II):

18. The method according to claim 16, wherein the compound is selected from the group consisting of:

19. The method according to claim 16, wherein the compound is FIN56:

20. The method according to claim 16, wherein the cell is mammalian.