IP Library › Granted Patent US 7,034,014
Granted Patent B2
US 7,034,014 · App. 10/759,345 · Granted Apr 25, 2006

Phosphonate compounds

Assignee: The Regents of the University of California
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Quick Facts
Patent No.
US 7,034,014
App. No.
10/759,345
Granted
Apr 25, 2006
Kind
B2
Abstract

The present invention relates to phosphonate compounds, compositions containing them, processes for obtaining them, and their use for treating a variety of medical disorders, e.g., osteoporosis and other disorders of bone metabolism, cancer, viral infections, and the like.

Claims (75)

1. A compound, having a phosphonate ester formed by a covalent linking of an antiviral compound selected from the group consisting of cidofovir, adefovir, cyclic cidofovir and tenofovir, to an alcohol selected from the group consisting of an alkylglycerol, alkylpropanediol, 1-S-alkylthioglycerol, alkoxyalkanol or alkylethanediol, or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein the antiviral compound is cidofovir.

3. The compound of claim 2 , wherein the alcohol is an alkylpropanediol.

4. The compound of claim 2 , wherein the alcohol is an alkylethanediol.

5. The compound of claim 2 , wherein the alcohol is an alkoxyalkanol.

6. The compound of claim 2 wherein the alcohol is an alkylglycerol.

7. The compound of claim 2 , wherein the alcohol is an 1-S-alkylthioglycerol.

8. The compound of claim 1 , wherein the antiviral compound is adefovir.

9. The compound of claim 8 , wherein the alcohol is an alkylpropanediol.

10. The compound of claim 8 , wherein the alcohol is an alkylethanediol.

11. The compound of claim 8 , wherein the alcohol is an alkoxyalkanol.

12. The compound of claim 8 , wherein the alcohol is an alkylglycerol.

13. The compound of claim 8 , wherein the alcohol is an 1-S-alkylthioglycerol.

14. The compound of claim 1 , wherein the antiviral compound is cyclic cidofovir.

15. The compound of claim 14 wherein the alcohol is an alkylpropanediol.

16. The compound of claim 14 , wherein the alcohol is an alkylethanediol.

17. The compound of claim 14 , wherein the alcohol is an alkoxyalkanol.

18. The compound of claim 14 , wherein the alcohol is an alkylglycerol.

19. The compound of claim 14 , wherein the alcohol is an 1-S-alkylthioglycerol.

20. The compound of claim 1 , wherein the antiviral compound is tenofovir.

21. The compound of claim 20 , wherein the alcohol is an alkylpropanediol.

22. The compound of claim 20 , wherein the alcohol is an alkylethanediol.

23. The compound of claim 20 , wherein the alcohol is an alkoxyalkanol.

24. The compound of claim 20 , wherein the alcohol is an alkylglycerol.

25. The compound of claim 20 wherein the alcohol is an 1-S-alkylthioglycerol.

26. The compound of claim 1 , wherein the phosphonate ester is formed by linking the antiviral compound to the alcohol through the 3-position of the alkylglycerol, alkylpropanediol, or 1-S-alkylthioglycerol.

27. The compound of claim 1 , wherein the phosphonate moiety in the ester is a phosphonate or a methylene phosphonate.

28. The compound of claim 1 , wherein the alcohol is an alkylpropanediol.

29. The compound of claim 26 , wherein the antiviral compound is cidofovir.

30. The compound of claim 28 , wherein the alkylpropanediol is 1-O-hexadecylpropanediol or 1-octadecylpropanediol.

31. The compound of claim 28 , wherein the alkylpropanediol is 1-O-hexadecylpropanediol or 1-O-octadecylpropanediol and the antiviral compound is cyclic cidofovir.

32. The compound of claim 28 , wherein the alkylpropanediol is 1-O-octadecylpropanediol.

33. The compound of claim 1 , wherein the alcohol is an alkylethanediol.

34. The compound of claim 30 , wherein the antiviral compound is cidofovir.

35. The compound of claim 33 , wherein the alkylethanediol is 1-O-octadecylethanediol.

36. The compound of claim 1 , wherein the alcohol is an alkylglycerol.

37. The compound of claim 36 , wherein the antiviral compound is cidofovir.

38. The compound of claim 36 , wherein the alkylglycerol is a 1-O-alkylglycerol.

39. The compound of claim 36 , wherein the alkylglycerol is a 3-O-alkylglycerol.

40. The compound of claim 38 , wherein the antiviral compound is cyclic cidofovir.

41. The compound of claim 39 , wherein the antiviral compound is cyclic cidofovir.

42. The compound of claim 39 , wherein the antiviral compound is cidofovir.

43. The compound of claim 38 , wherein the antiviral compound is adefovir.

44. The compound of claim 39 , wherein the antiviral compound is adefovir.

45. The compound of claim 38 , wherein the antiviral compound is tenofovir.

46. The compound of claim 39 , wherein the antiviral compound is tenofovir.

47. The compound of claim 1 , wherein the alcohol is a 1-S-alkylthioglycerol.

48. The compound of claim 1 , wherein the alcohol is an alkyoxyalkanol.

49. The compound of claim 48 , wherein the alkoxyalkanol is a 1-O-alkylpropane-3-ol.

50. The compound of claim 49 , wherein the antiviral compound is cidofovir.

51. The compound of claim 49 , wherein the antiviral compound is cyclic cidofovir.

52. The compound of claim 49 , wherein the antiviral compound is tenofovir.

53. The compound of claim 49 , wherein the antiviral compound is adefovir.

54. A method for the treatment of a viral disease selected from human immunodeficiency virus, influenza, herpes simplex virus, human herpes virus, cytomegalovirus, hepatitis B and C virus, Epstein-Barr virus, varicella zoster virus, orthopox virus, ebola virus and papilloma virus comprising administering an effective amount of a compound of claim 16 optionally in a pharmaceutically acceptable carrier.

55. The method of claim 54 wherein the virus is an orthopox virus selected from variola major and minor, vaccinia, smallpox, cowpox, camelpox and monkeypox.

56. The method of claim 54 , wherein the virus is human immunodeficiency virus.

57. The method of claim 54 , wherein the virus is influenza.

58. The method of claim 54 , wherein the virus is herpes.

59. The method of claim 54 , wherein the virus is cytomegalovirus.

60. The method of claim 54 , wherein the virus is hepatitis B.

61. The method of claim 54 , wherein the virus is hepatitis C.

62. The method of claim 54 , wherein the virus is Epstein-Barr virus.

63. The method of claim 54 , wherein the virus is varicella zoster virus.

64. The method of claim 54 , wherein the virus is papilloma.

65. The compound of claim 1 , having the following structure or a pharmaceutically acceptable salt thereof:

66. The compound of claim 1 , having the following structure or a pharmaceutically acceptable salt thereof:

67. 1-O-octadecylpropanediol-3-cidofovir.

68. 1-O-octadecylethanediol-2-cidofovir.

69. 1-O-hexadecylpropanediol-3-cidofovir.

70. 1-O-hexadecylpropanediol-3-cyclic cidofovir.

71. 1-O-octadecylpropanediol-3-cyclic cidofovir.

72. 1-O-octadecylethanediol-2-cyclic cidofovir.

73. 1-O-hexadecylpropanediol-3-adefovir.

74. 1-O-octadecyl-sn-glycero-3-adefovir.

75. A pharmaceutical composition comprising an effective amount of compound of any one of claims 1 and 65 – 74 in combination with a pharmaceutically acceptable carrier.

Assignments (1)
CONFIRMATORY LICENSE Recorded Aug 6, 2008
From: UNIVERSITY OF CALIFORNIA SAN DIEGO
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 021345/0243 →
Continuity (4)
Continuation 1014837400
Provisional Application 6020571900 · May 19, 2000
Provisional Application 6016881300 · Dec 3, 1999
Related Publication 20040127735A1 · Jul 1, 2004