Bis diselenide-based schiff bases as deubiquitination signaling pathway modulators

Patent metadata

Field	Value
Publication number	US-12006293-B1
Application number	US-202318545056-A
Country	US
Kind code	B1
Filing date	Dec 19, 2023
Priority date	Dec 19, 2023
Publication date	Jun 11, 2024
Grant date	Jun 11, 2024

Abstract

Diselenide organo compounds, their synthesis, and their use as deubiquitination signaling pathway modulators and anti-cancer agents.

First claim

We claim:

1. A diselenide organo compound having the formula:

wherein Ar is selected from the group consisting of a pyrazole, a pyridine, and an indole, and wherein said Ar is optionally substituted with a chlorine, a hydroxy, or a pyridine.

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

3. A pharmaceutically acceptable composition comprising a therapeutically effective amount of the diselenide organo compound of claim 1 and a pharmaceutically acceptable carrier.

4. The pharmaceutically acceptable composition of claim 3 , wherein the diselenide organo compound is selected from the group consisting of:

5. A method of inhibiting Ubiquitin-specific proteases in a subject comprising administering to a subject in need thereof a therapeutically effective amount of the diselenide organo compound of claim 1 .

6. The method of inhibiting Ubiquitin-specific proteases in a patient of claim 5 , wherein the Ubiquitin-specific proteases are selected from the group consisting of USP7 and USP9X.

7. The method of inhibiting Ubiquitin-specific proteases of claim 5 , wherein the diselenide organo compound is selected from the group consisting of:

8. A method of restoring p53 function in a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of the diselenide organo compound of claim 1 .

9. The method of restoring p53 function of claim 8 , wherein the diselenide organo compound is selected from the group consisting of:

10. A method of inducing cancer death in a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of the diselenide organo compound of claim 1 .

11. The method of inducting cancer death of claim 10 , wherein the diselenide organo compound is selected from the group consisting of:

12. A method of treating cancer in a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of the diselenide organo compound of claim 1 .

13. The method of treating cancer of claim 12 , wherein the diselenide organo compound is selected from the group consisting of:

14. A method of making the diselenide organo compound of claim 1 , the method comprising:
adding an aldehyde to a bis diselenide Schiff base in ethanol to obtain a reaction mixture;
adding a catalyst to the reaction mixture;
refluxing the reaction mixture;
cooling the reaction mixture to obtain a formed precipitate;
filtering and recrystallizing the formed precipitate from ethanol; and
obtaining the diselenide organo compound.

15. The method of making the diselenide organo compounds of claim 14 , wherein the aldehyde is 4-chloro-1H-pyrazole-3-carboxaldehyde and the diselenide organo compound is diselenide bis (4-chloro-1H-pyrazole-3-carboxaldehyde).

16. The method of making the diselenide organo compounds of claim 14 , wherein the aldehyde is 3-hydroxypyridine-2-carboxaldehyde and the diselenide organo compound is diselenide bis (3-hydroxypyridine-2-carboxaldehyde).

17. The method of making the diselenide organo compounds of claim 14 , wherein the aldehyde is 2-pyridin-3-yl-1H-indole-3-carboxaldehyde and the diselenide organo compound is diselenide bis (2-pyridin-3-yl-1H-indole-3-carboxaldehyde).

18. The method of making the diselenide organo compounds of claim 14 , wherein the catalyst is acetic acid.

19. The method of making the diselenide organo compounds of claim 14 , wherein about 1 equivalent of the aldehyde is added to about −0.5 equivalents of the diselenide Schiff base.

20. The method of making the diselenide organo compounds of claim 14 , wherein the reaction mixture is refluxed for at least 6 hours.

Assignees

• Univ King Faisal

Inventors

• Shaaban Saad
• Negm Amr

Classifications

• A61K31/4375

  the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine · CPC title

• C07D231/12 Primary

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms · CPC title

• A61K31/4155

  non condensed and containing further heterocyclic rings · CPC title

• C07D213/65

  attached in position 3 or 5 · CPC title

• C07D401/14 Primary

  containing three or more hetero rings · CPC title