Compound for inhibition of delta-5-desaturase (D5D) and treatment of cancer and inflammation

• US 10,639,313 B2
• Filed: 08/31/2018
• Issued: 05/05/2020
• Est. Priority Date: 09/01/2017
• Status: Active Grant

• Current Assignee: Ndsu-Research Foundation
• Original Assignee: Ndsu-Research Foundation
• Inventors: Qian, Yue (Steven), Zhao, Pinjing, Yan, Changhui
• Primary Examiner(s): Shiao, Rei Tsang
• Application Number:
  US16/118,991
• Publication Number:
  US 20190070193A1
• Time in Patent Office: 613 Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07D 223/22 Dibenz [b, f] azepines; Hydrogenated dibenz [b, f] azepines

Abstract

Tricyclic compounds, including tricyclic iminodibenzylic and tricyclic iminostilbene compounds, are identified as therapeutic agents for inhibition of delta-5-desaturase (D5D) and for treating or preventing cancer and precancerous conditions, as well as autoimmune and inflammatory conditions. Pharmaceutical compositions and dietary supplements are provided, as are methods of administration and treatment.

Claims

1. A method for treating or preventing cancer or a precancerous condition in a subject, the method comprising administering to the subject a composition comprising an effective amount of a compound, wherein the subject is afflicted with or at risk of having a cancer characterized by high COX-2 expression, wherein the compound is an iminodibenzyl or a derivative thereof, wherein the iminodibenzyl has the formula:

2. The method of claim 1, wherein the cancer is a cancer of the colon, rectum, breast, prostate, liver, pancreas, bone, brain, ovary, cervix, larynx, lung, esophagus, testicle, skin, spine, stomach, bladder, kidney, uterus, thyroid, blood or immune system.

8. The method of claim 2, wherein the cancer is colorectal cancer.

9. The method of claim 2, wherein the subject has a risk factor for developing cancer or a precancerous condition, and wherein the compound is administered prior to the development of a cancer or precancerous condition.

10. The method of claim 2 wherein the subject is afflicted with a cancer that is therapy-refractory.

11. The method of claim 1, wherein R₁ and R₂ are each independently selected from H, —

CH₃, —

OCH₃, —

OH, —

CH(CH₃)₂, —

C(CH₃)₃, —

N(CH₃)₂, —

F or —

CF₃, provided that at least one of R₁ and R₂ is not H.

12. The method of claim 1, wherein R₁ and R₂ are positioned at the (1, 9) ring positions, the (3, 7) ring positions, or the (4, 6) ring positions.

13. The method of claim 1, wherein R₁ and R₂ are positioned at the (1, 9) ring positions.

14. The method of claim 1, wherein R₁ is H and R₂ is positioned at the 1, 2, 3, or 4 ring position.

15. The method of claim 1, wherein R₁ is H and R₂ is positioned at the 1 ring position.

16. The method of claim 1, wherein the derivative has a (10, 11)-dihydro dibenzazepine moiety.

17. The compound of claim 1, wherein the derivative has a dibenzazepine moiety.

18. The method of claim 1, wherein R₁=R₂.

19. The compound of claim 1, wherein R₁≠

R₂.

3. A method for inhibiting the growth of a tumor in a subject, the method comprising:

administering to the subject a composition comprising an effective amount a compound, wherein the subject is afflicted with a tumor characterized by high COX-2 expression, wherein the compound is an iminodibenzyl or a derivative thereof, wherein the iminodibenzyl has the formula;

4. The method of claim 3, wherein the tumor comprises a solid tumor disposed in the colon, rectum, breast, prostate, liver, pancreas, bone, brain, ovary, cervix, larynx, lung, esophagus, testicle, skin, spine, stomach, bladder, kidney, uterus, thyroid, or immune system of the subject.

5. A method for treating or preventing cancer metastasis, migration, or invasion in a subject, the method comprising administering to the subject a composition comprising an effective amount of a compound, wherein the subject is afflicted with or at risk of having a cancer metastasis, migration, or invasion characterized by high COX-2 expression, wherein the compound is an iminodibenzyl or a derivative thereof, wherein the iminodibenzyl has the formula:

6. The method of claim 5, wherein the cancer is a cancer of the colon, rectum, breast, prostate, liver, pancreas, bone, brain, ovary, cervix, larynx, lung, esophagus, testicle, skin, spine, stomach, bladder, kidney, uterus, thyroid, blood or immune system.

7. A method for treating or preventing cancer or a precancerous condition in a subject, inhibiting the growth of a tumor in a subject, or treating or preventing cancer metastasis, migration, or invasion in a subject, the method comprising

providing a kit comprising a compound, wherein the compound is an iminodibenzyl or a derivative thereof, wherein the iminodibenzyl has the formula: