Nitroxyl donors with improved therapeutic index
The disclosed subject matter provides N-substituted hydroxylamine derivative compounds, pharmaceutical compositions and kits comprising such compounds, and methods of using such compounds or pharmaceutical compositions. In particular, the disclosed subject matter provides methods of using such compounds or pharmaceutical compositions for treating heart failure.
1. A compound of formula (1):
2. A method of treating a cardiovascular disease, comprising administering an effective amount of the compound of claim 1 to a patient in need thereof.
3. The method of claim 2 , wherein the compound is administered intravenously.
4. The method of claim 2 , wherein the cardiovascular disease is heart failure.
5. The method of claim 4 , wherein the compound is administered intravenously.
6. The method of claim 2 , wherein the cardiovascular disease is acute decompensated heart failure.
7. The method of claim 6 , wherein the compound is administered intravenously.
8. A pharmaceutical composition comprising the compound of claim 1 and at least one pharmaceutically acceptable excipient.
9. The pharmaceutical composition of claim 8 , wherein the pharmaceutical composition is suitable for intravenous administration.
10. The pharmaceutical composition of claim 8 , wherein the at least one pharmaceutically acceptable excipient is at least one species of cyclodextrin.
11. The pharmaceutical composition of claim 10 , wherein the pharmaceutical composition is suitable for intravenous administration.
12. A method of treating a cardiovascular disease, comprising administering an effective amount of the pharmaceutical composition of claim 8 to a patient in need thereof.
13. The method of claim 12 , wherein the pharmaceutical composition is administered intravenously.
14. The method of claim 12 , wherein the cardiovascular disease is heart failure.
15. The method of claim 14 , wherein the pharmaceutical composition is administered intravenously.
16. The method of claim 12 , wherein the cardiovascular disease is acute decompensated heart failure.
17. The method of claim 16 , wherein the pharmaceutical composition is administered intravenously.
18. A compound of formula (2):
19. A method of treating a cardiovascular disease, comprising administering an effective amount of the compound of claim 18 a to patient in need thereof.
20. The method of claim 19 , wherein the compound is administered intravenously.
21. The method of claim 19 , wherein the cardiovascular disease is heart failure.
22. The method of claim 21 , wherein the compound is administered intravenously.
23. The method of claim 19 , wherein the cardiovascular disease is acute decompensated heart failure.
24. The method of claim 23 , wherein the compound is administered intravenously.
25. A pharmaceutical composition comprising the compound of claim 18 and at least one pharmaceutically acceptable excipient.
26. The pharmaceutical composition of claim 25 , wherein the pharmaceutical composition is suitable for intravenous administration.
27. The pharmaceutical composition of claim 25 , wherein the at least one pharmaceutically acceptable excipient is at least one species of cyclodextrin.
28. The pharmaceutical composition of claim 27 , wherein the pharmaceutical composition is suitable for intravenous administration.
29. A method of treating a cardiovascular disease, comprising administering an effective amount of the pharmaceutical composition of claim 25 to a patient in need thereof.
30. The method of claim 29 , wherein the pharmaceutical composition is administered intravenously.
31. The method of claim 29 , wherein the cardiovascular disease is heart failure.
32. The method of claim 31 , wherein the pharmaceutical composition is administered intravenously.
33. The method of claim 29 , wherein the cardiovascular disease is acute decompensated heart failure.
34. The method of claim 33 , wherein the pharmaceutical composition is administered intravenously.