Mito-magnolol compounds and methods of synthesis and use thereof

Patent metadata

Field	Value
Publication number	US-11083739-B2
Application number	US-201916714461-A
Country	US
Kind code	B2
Filing date	Dec 13, 2019
Priority date	Dec 14, 2018
Publication date	Aug 10, 2021
Grant date	Aug 10, 2021

Abstract

The present invention provides mito-magnolol compounds, pharmaceutical compositions thereof, and methods of using the mito-magnolol compounds in the treatment of cancer, especially anti-cancer therapy or kinase resistant cancers.

First claim

We claim:

1. A mito-magnolol compound of formula (I)

wherein
X is selected from a C 1 -C 18 alkyl, phenyl and polyethylene glycol (PEG);
Each Y is independently selected from —H, —CF 3 , methyl (Me), Cl, OMe, C(O)CH 3 , NO 2 , N(Me) 2 ;
and R is selected from C 1 -C 18 alkyl, phenyl, benzyl and polyethylene glycol (PEG).

2. The mito-magnolol compound of claim 1 , wherein X is C 1 -C 18 alkyl and each Y is H.

3. The mito-magnolol compound of claim 1 , wherein the compound is:

4. The mito-magnolol compound of claim 1 , wherein the compound is:

5. A composition comprising the mito-magnolol compound of claim 1 and a pharmaceutically acceptable carrier.

6. A method of treating cancer in a subject having cancer comprising:
administering the mito-magnolol compound of claim 1 in a therapeutically effective amount to treat the cancer,
wherein the cancer is melanoma.

7. The method of claim 6 , wherein the cancer is resistant to anti-cancer therapy.

8. The method of claim 7 , wherein the anti-cancer therapy is a BRAF inhibitor.

9. The method of claim 7 , wherein the anti-cancer therapy is a checkpoint inhibitor.

10. The method of claim 6 , wherein the mito-magnolol compound is administered in combination with one or more additional anti-cancer therapies.

11. The method of claim 10 , wherein the anti-cancer therapy is a BRAF inhibitor.

12. A method of reducing or inhibiting cancer cell growth in a subject having cancer, the method comprising:
administering the mito-magnolol compound of claim 1 in a therapeutically effective amount to reduce or inhibit cancer cell growth,
wherein the cancer is melanoma.

13. The method of claim 12 , wherein the mito-magnolol compound is administered in combination with one or more anti-cancer therapies.

14. A method of preventing or delaying resistance of a cancer to an anti-cancer therapy in a subject, the method comprising:
administering the mito-magnolol compound of claim 1 in a therapeutically effective amount to prevent or delay resistance of the cancer to the anti-cancer therapy,
wherein the cancer is melanoma.

15. The method of claim 14 , wherein the mito-magnolol compound is administered in combination with an anti-cancer therapy.

16. The method of claim 15 , wherein the anti-cancer therapy is co-currently administered.

17. A method of increasing a T cell response to an anti-cancer therapy in a cancer patient, the method comprising administering the mito-magnolol compound of claim 1 in a therapeutically effective amount to increase the T cell response to the anti-cancer therapy,
wherein the cancer is melanoma.

18. The method of claim 17 , wherein the anti-cancer therapy is an inhibitor of an oncogenic kinase.

19. The method of claim 17 , wherein the anti-cancer therapy is a checkpoint inhibitor.

20. The method of claim 17 , wherein the mito-magnolol compound is administered in combination with one or more anti-cancer therapies.

21. A kit comprising at least one mito-magnolol compound of claim 1 , a pharmaceutically acceptable carrier or diluent, and instructional material.

Assignees

• Medical College Wisconsin Inc
• Aix Marseille Univ

Inventors

• Kalyanaraman Balaraman
• Zielonka Jacek Michal
• Cheng Gang
• Hardy Micael Joël
• Ouari Olivier

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07F9/54

  Quaternary phosphonium compounds · CPC title

• A61K31/66 Primary

  Phosphorus compounds · CPC title

• A61K45/06

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

• C07F9/5442 Primary

  Aromatic phosphonium compounds (P-C aromatic linkage) · CPC title