COMPOUND FOR INHIBITION OF DELTA-5-DESATURASE (D5D) AND TREATMENT OF CANCER AND INFLAMMATION

• US 20190070193A1
• Filed: 08/31/2018
• Published: 03/07/2019
• 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
• Granted Patent: US 10,639,313 B2
• Time in Patent Office: 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 compound having Formula (Ia) or Formula (Ib)

2. The compound 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.

3. The compound 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.

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

7. The compound of claim 1, comprising a (10,11)-dihydro dibenzazepine moiety.

8. The compound of claim 1, comprising a dibenzazepine moiety.

10. The compound of claim 1 wherein R₁=R₂.

11. The compound of claim 1 wherein R₁≠

R₂.

13. The compound of claim 1, which inhibits the activity of delta-5-desaturase (D5D).

14. A pharmaceutical composition comprising:

an active agent comprising a compound according to claim 1; and

a pharmaceutically acceptable carrier.

17. 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 claim 1.

18. The method of claim 17, 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.

21. 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 of claim 1.

22. The method of claim 21, 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.

25. 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 of claim 1.

26. The method of claim 25, 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.

28. A method for treating 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 of claim 1;

and

providing a label that comprises instructions for a dosage regimen comprising dosing amount, frequency of dosing, or a combination thereof.

29. A method for inhibiting the activity of delta-5-destaturse (D5D) in a subject, the method comprising:

administering to the subject a composition comprising an effective amount a compound of claim 1.

30. A method for treating or preventing an autoimmune or inflammatory condition in a subject, the method comprising:

administering to the subject a composition comprising an effective amount a compound of claim 1.

31. A method for inhibiting the activity of delta-5-destaturase (D5D), the method comprising:

contacting a composition comprising D5D with a compound of claim 1; and

determining if the activity of D5D is inhibited.

4. (canceled)

6. (canceled)

9. (canceled)

12. (canceled)

15-16. -16. (canceled)

19-20. -20. (canceled)

23-24. -24. (canceled)

27. (canceled)

32-35. -35. (canceled)