Compounds and compositions for use in phototherapy and in treatment of ocular neovascular disease and cancers

• US 9,527,858 B2
• Filed: 06/26/2014
• Issued: 12/27/2016
• Est. Priority Date: 07/16/2009
• Status: Active Grant

• Current Assignee: SpecGx LLC (Mallinckrodt plc)
• Original Assignee: Mallinckrodt LLC (Mallinckrodt plc)
• Inventors: Cantrell, Gary L., Rajagopalan, Raghavan, Karwa, Amolkumar, Dorshow, Richard B.
• Primary Examiner(s): Otton, Alicia L
• Application Number:
  US14/316,443
• Publication Number:
  US 20140370006A1
• Time in Patent Office: 915 Days
• Field of Search: None
• US Class Current: 1/1
• 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 31/472 Non-condensed isoquinolines, e.g. papaverine
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 41/0057 Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61K 9/02 Suppositories; Bougies; Bases therefor; Ovulesapparatus for making A61J3/08; devices for introducing into the body A61M31/00
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2022 Organic macromolecular compounds
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2059 Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: C07D 221/28 : Morphinans
• CPC Class Codes: C07D 489/02 : with oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone

Abstract

The invention relates generally to anti-angiogenesis agents and related methods of using to anti-angiogenesis agents for biomedical applications including direct monotherapy and combination therapy for treatment of an angiogenesis related condition. In an embodiment, the invention provides a class of opioid compounds and structurally related opioid derivatives exhibiting anti-VEGF activity for use in therapeutic procedures, including phototherapy. Opioid compounds and structurally related opioid derivatives of the invention may be administered alone or in combination with administration of a phototherapy agent and/or other therapeutic agent.

Claims

1. A method for treating cancer, the method comprising:

administering to a patient in need of treatment an effective amount of a purified (+) enantiomer compound substantially free of a corresponding (−

) enantiomer, the (+) enantiomer compound having the formula (FX1);

2. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX11):

3. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX15):

4. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX17):

5. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX20):

6. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX22):

7. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX24):

8. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX26):

9. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX28):

10. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX29):

11. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX31)

12. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX33):

13. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX35):

14. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX37):

15. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX40):

16. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX42):

17. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX44):

18. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX46):

19. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX48):

20. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX49).

21. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX51):

22. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX53):

23. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX55):

24. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX57):

25. The method of claim 1 wherein said (+) enantiomer compound has the formula (FX59):

26. The method of claim 1 wherein said (+) enantiomer compound has the formula:

27. The method for treating cancer of claim 1, further comprising administering to said patient a mixture of two or more purified (+) enantiomer compounds each independently having a formula (FX1).

28. The method of claim 1, comprising a method for treating pancreatic cancer.

29. The method of claim 1, comprising a method of suppressing tumor growth or tumor metastasis.

30. The method of claim 1, further comprising administering to said patient one or more chemotherapeutic agents.

31. The method of claim 1, further comprising administering to said patient one or more VEGF inhibitors.

32. The method of claim 1, further comprising administering to said patient 5-fluorouracil, floxuridine, furtulon, capecitabine, gemcitabine, taxol, doxorubicin, cisplatin, thalidomide, paclitaxel, docetaxel or bevacizumab.

33. A method for treating cancer, the method comprising:

administering to a patient in need of treatment an effective amount of a purified (+) enantiomer compound substantially free of a corresponding (−

) enantiomer, the (+) enantiomer compound having the formula (FX13);

34. The method of claim 33, wherein said (+) enantiomer compound has the formula (FX72):

35. The method of claim 33, wherein said (+) enantiomer compound has the formula (FX74):

36. The method of claim 33, wherein said (+) enantiomer compound has the formula (FX80):

37. The method of claim 33, wherein said (+) enantiomer compound has the formula (FX82):

38. The method of claim 33, wherein said (+) enantiomer compound has the formula (FX84):

39. The method of claim 33, wherein said (+) enantiomer compound has the formula (FX87):

40. The method of claim 33, wherein said (+) enantiomer compound has the formula (FX100):

41. The method for treating cancer of claim 33 further comprising administering to said patient a mixture of two or more purified (+) enantiomer compounds each independently having a formula (FX13).

42. The method of claim 33, comprising a method for treating pancreatic cancer.

43. The method of claim 33, comprising a method of suppressing tumor growth or tumor metastasis.

44. The method of claim 33, further comprising administering to said patient one or more chemotherapeutic agents.

45. The method of claim 33, further comprising administering to said patient one or more VEGF inhibitors.

46. The method of claim 33, further comprising administering to said patient 5-fluorouracil, floxuridine, furtulon, capecitabine, gemcitabine, taxol, doxorubicin, cisplatin, thalidomide, paclitaxel, docetaxel or bevacizumab.

47. A method for treating cancer, the method comprising:

administering to a patient in need of treatment an effective amount of a purified (+) enantiomer compound substantially free of a corresponding (−

) enantiomer, the (+) enantiomer compound having the formula (FX15);

48. The method of claim 47, wherein said (+) enantiomer compound has the formula (FX92):

49. The method of claim 47, wherein said (+) enantiomer compound has the formula (FX95):

50. The method of claim 47, wherein said (+) enantiomer compound has the formula (FX106):

51. The method for treating cancer of claim 47, further comprising administering to said patient a mixture of two or more purified (+) enantiomer compounds each independently having a formula (FX15).

52. The method of claim 47, comprising a method for treating pancreatic cancer.

53. The method of claim 47, comprising a method of suppressing tumor growth or tumor metastasis.

54. The method of claim 47, further comprising administering to said patient one or more chemotherapeutic agents.

55. The method of claim 47, further comprising administering to said patient one or more VEGF inhibitors.

56. The method of claim 47, further comprising administering to said patient 5-fluorouracil, floxuridine, furtulon, capecitabine, gemcitabine, taxol, doxorubicin, cisplatin, thalidomide, paclitaxel, docetaxel or bevacizumab.