Treatment of hyperproliferative disorders with diarylhydantoin compounds

• US 8,183,274 B2
• Filed: 02/18/2010
• Issued: 05/22/2012
• Est. Priority Date: 05/13/2005
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Sawyers, Charles L., Jung, Michael E., Chen, Charlie D., Ouk, Samedy, Tran, Chris, Wongvipat, John
• Primary Examiner(s): Chu, Yong
• Assistant Examiner(s): BARKER, MICHAEL P
• Application Number:
  US12/708,523
• Publication Number:
  US 20100172975A1
• Time in Patent Office: 824 Days
• Field of Search: None
• US Class Current: 514/391
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 233/70 One oxygen atom
• CPC Class Codes: C07D 233/74 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to other ring members
• CPC Class Codes: C07D 233/86 Oxygen and sulfur atoms, e.g. thiohydantoin
• CPC Class Codes: C07D 235/02 condensed with carbocyclic rings or ring systems
• CPC Class Codes: C07D 471/10 Spiro-condensed systems

Abstract

The present invention relates to diarylhydantoin compounds, including diarylthiohydantoins, and methods for synthesizing them and using them in the treatment of hormone refractory prostate cancer.

Claims

1. A method for treating prostate cancer comprising administering a therapeutically effective amount of a compound selected from the group consisting of

2. The method of claim 1, wherein the compound is administered at a dosage in the range of from about 0.001 mg per kg body weight per day to about 100 mg per kg body weight per day.

3. The method of claim 1, wherein the compound is administered at a dosage in the range of from about 1 mg per kg body weight per day to about 10 mg per kg body weight per day.

4. The method of claim 1, wherein the compound is administered at a dosage in the range of from about 0.1 mg per kg body weight per day to about 10 mg per kg body weight per day.

5. The method of claim 1, wherein the compound is administered at a dosage of about 1 mg per kg body weight per day.

6. The method of claim 1, wherein the prostate cancer is hormone refractory prostate cancer.

7. The method of claim 1, wherein the compound is administered by intravenous injection, by injection into tissue, intraperitoneally, orally, topically, or nasally.

8. The method of claim 1, wherein the compound is administered orally.

9. The method of claim 1, wherein the compound is administered in a form selected from the group consisting of a solution, dispersion, suspension, powder, capsule, tablet, pill, time release capsule, time release tablet, and time release pill.

10. The method of claim 1, wherein the compound is administered in a form selected from the group consisting of a capsule, tablet, and pill.

11. The method of claim 1, wherein the prostate cancer is hormone sensitive prostate cancer.

12. The method of claim 1, wherein the compound is

13. The method of claim 1, wherein the compound is administered with a pharmaceutically acceptable carrier or diluent.

14. The method of claim 13, wherein the pharmaceutically acceptable carrier or diluent comprises one or more of dimethylsulfoxide (DMSO), polyethylene glycol (PEG), and water.

15. The method of claim 1, wherein the compound is administered at a dosage of about 2 mg per kg body weight per day.

16. The method of claim 1, wherein the compound is administered to achieve a peak plasma concentration in the range of from about 0.5 μ

M to about 75 μ

M.

17. The method of claim 1, wherein the compound is administered to achieve a peak plasma concentration of about 10 μ

M.

18. The method of claim 1, wherein the compound is administered to achieve a steady state plasma concentration of from about 5 μ

M to about 100 μ

M.

19. The method of claim 1, wherein the compound is administered to achieve a steady state plasma concentration of from about 10 μ

M to about 50 μ

M.

20. The method of claim 1, wherein the compound is administered to achieve a steady state plasma concentration of about 25 μ

M.

21. The method of claim 1, wherein the compound is administered daily.

22. The method of claim 1, wherein the compound is administered three times per day.

23. The method of claim 1, wherein the compound is administered in a unit dosage form comprising from about 5 mg to about 1000 mg of active ingredient per unit dosage form.

24. The method of claim 1, wherein the compound is administered in a unit dosage form comprising about 100 mg of active ingredient per unit dosage form.

26. The method of claim 1, wherein the compound is

27. The method of claim 1, wherein the compound is

31. The method of claim 12, wherein the prostate cancer is hormone refractory prostate cancer.

32. The method of claim 12, wherein the prostate cancer is hormone sensitive prostate cancer.

25. A method for treating benign prostate hyperplasia comprising administering a therapeutically effective amount of a compound selected from the group consisting of

28. The method of claim 25, wherein the compound is

29. The method of claim 25, wherein the compound is

30. The method of claim 25, wherein the compound is

33. A method for treating breast cancer comprising administering a therapeutically effective amount of a compound selected from the group consisting of

34. The method of claim 33, wherein the compound is

35. The method of claim 33, wherein the compound is

36. The method of claim 33, wherein the compound is

37. A method for treating ovarian cancer comprising administering a therapeutically effective amount of a compound selected from the group consisting of

38. The method of claim 37, wherein the compound is

39. The method of claim 37, wherein the compound is

40. The method of claim 37, wherein the compound is