Phosphonate compounds
View Patent ↗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.
1. A compound having the structure of Formula I:
R 3 —O(CH 2 ) a —R 1 (I)
wherein:
R 1 is —O—(CH 2 ) t —CH 3 , wherein t is 11 to 19;
a is 2 to 4;
R 3 is either Formula II or Formula III:
B is selected from the group consisting of hydrogen, —CH 3 , and —CH 2 OH,
Z is
and the symbol * indicates that —*CH 2 — in Formula II or Formula III is attached to Z via N* in Formula A or B, or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein said compound is in the form of an enantiomer, diastereomer, racemate, or a mixture thereof.
3. A pharmaceutical composition comprising an effective amount of a compound having the structure of Formula I:
R 3 —O(CH 2 ) a —R 1 (I)
wherein:
R 1 is —O—(CH 2 ) t —CH 3 , wherein t is 11 to 19;
a is 2 to 4;
R 3 is either Formula II or Formula III:
B is selected from the group consisting of hydrogen, —CH 3 , and —CH 2 OH,
Z is
and the symbol * indicates that —*CH 2 — in Formula II or Formula III is attached to Z via N* in Formula A or B, or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier.
4. The pharmaceutical composition of claim 3 in a solid dosage form.
5. The pharmaceutical composition of claim 3 in a capsule, tablet, aerosol, solution, suspension, or in a topical formulation.
6. A method for the treatment of a viral disease selected from the group consisting of human immunodeficiency virus (HIV), influenza, herpes simplex virus, human herpes virus, cytomegalovirus, hepatitis B virus, hepatitis C virus, Epstein-Barr virus, varicella zoster virus, orthopox virus, ebola virus and papilloma virus comprising administering an effective amount of a compound having the structure of Formula I:
R 3 —O(CH 2 ) a —R 1 (I)
wherein:
R 1 is —O—(CH 2 ) t —CH 3 , wherein t is 11 to 19;
a is 2 to 4;
R 3 is either Formula II or Formula III:
B is selected from the group consisting of hydrogen, —CH 3 , and —CH 2 OH,
Z is
and the symbol * indicates that —*CH 2 — in Formula II or Formula III is attached to Z via N* in Formula A or B, or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier.
7. The method of claim 6 , wherein the orthopox is selected from the group consisting of variola major, variola minor, vaccinia, smallpox, cowpox, camelpox and monkeypox.
8. The method of claim 6 , wherein the virus is HIV.
9. The method of claim 6 , wherein the virus is influenza.
10. The method of claim 6 , wherein the virus is herpes.
11. The method of claim 6 , wherein the virus is cytomegalovirus.
12. The method of claim 6 , wherein the virus is hepatitis B.
13. The method of claim 6 , wherein the virus is hepatitis C.
14. The method of claim 6 , wherein the virus is Epstein-Barr virus.
15. The method of claim 6 , wherein the virus is varicella zoster virus.
16. The method of claim 6 , wherein the virus is papilloma.
17. A pharmaceutical composition comprising a compound having the structure (A) or a pharmaceutically acceptable salt thereof
and a pharmaceutically acceptable carrier, wherein the pharmaceutical composition is in a solid dosage form.
18. A pharmaceutical composition comprising a compound having the structure (A) or a pharmaceutically acceptable salt thereof
and a pharmaceutically acceptable carrier, wherein the pharmaceutical composition is in a capsule, tablet, aerosol, solution, suspension, or in a topical formulation.
19. The compound of claim 1 , wherein a is 3 and t is 15 or 17.
20. The method of claim 6 , wherein Z is
21. The method of claim 6 , wherein a is 3 and t is 15 or 17.
22. The method of claim 6 , wherein Z is
23. The compound of claim 1 , wherein a is 3; t is 15 or 17; R 3 has Formula II; B is —CH 2 OH; and Z is
or a pharmaceutically acceptable salt thereof.
24. The compound of claim 1 , wherein a is 3; t is 15 or 17; R 3 has Formula II; B is CH 3 ; and Z is
or a pharmaceutically acceptable salt thereof.
25. The compound of claim 1 , wherein a is 3; t is 15 or 17; R 3 has Formula II; B is H; and Z is
or a pharmaceutically acceptable salt thereof.
26. The compound of claim 1 , wherein a is 3; t is 15 or 17; R 3 has Formula III; and Z is
or a pharmaceutically acceptable salt thereof.
27. The compound of claim 1 , the compound having the structure:
or a pharmaceutically acceptable salt thereof.
28. The compound of claim 1 , the compound having the structure:
or a pharmaceutically acceptable salt thereof.
29. The method of claim 6 , wherein a is 3; t is 15 or 17; R 3 has Formula II; B is —CH 2 OH; and Z is
or a pharmaceutically acceptable salt thereof.
30. The method of claim 6 , wherein a is 3; t is 15 or 17; R 3 has Formula II; B is CH 3 ; and Z is
or a pharmaceutically acceptable salt thereof.
31. The method of claim 6 , wherein a is 3; t is 15 or 17; R 3 has Formula II; B is H; and Z is
or a pharmaceutically acceptable salt thereof.
32. The method of claim 6 , wherein a is 3; t is 15 or 17; R 3 has Formula III; and Z is
or a pharmaceutically acceptable salt thereof.
33. The method of claim 6 , wherein the compound has the structure:
or a pharmaceutically acceptable salt thereof.
34. The method of claim 6 , wherein the compound has the structure:
or a pharmaceutically acceptable salt thereof.
35. The method of claim 6 , wherein the compound is topically administered.
36. The method of claim 35 , wherein the compound is administered as a spray.
37. The method of claim 35 , wherein the compound is administered through the skin by an appliance.
38. The method of claim 37 , wherein the compound is administered through the skin by a transdermal patch.
39. The method of claim 6 , wherein the compound is rectally administered.
40. The method of claim 6 , wherein the compound is applied though nasal administration.
41. The method of claim 6 , wherein the compound is parenterally administered.
42. The method of claim 6 , wherein the compound is administered through subcutaneous, intravenous, intra-arterial, intramuscular, intravitaeal injection or infusion.
43. The method of claim 6 , wherein the compound is administered orally.
44. The method of claim 43 , wherein the compound is administered orally in the form of tablets, capsules, solutions, emulsions or suspensions, inhalded liquid, solid particles, microencapsulated particles.
45. The method of claim 6 , wherein the compound is
or a pharmaceutically acceptable salt thereof, and the viral disease is HIV and/or hepatitis B.
46. The method of claim 6 , wherein the viral disease is human herpes virus.
47. The method of claim 6 , wherein the viral disease is ebola virus.