Compounds, compositions and methods
Certain substituted urea derivatives selectively modulate the cardiac sarcomere, for example by potentiating cardiac myosin, and are useful in the treatment of systolic heart failure including congestive heart failure.
1. A compound that is methyl 4-[(3-fluoro-5-{[(6-methyl(3-pyridyl))amino]carbonylamino}-phenyl)methyl]piperazinecarboxylate
or a pharmaceutically acceptable salt thereof.
2. A pharmaceutical composition comprising a pharmaceutically acceptable excipient, carrier or adjuvant and a compound of claim 1 , or a pharmaceutically acceptable salt thereof.
3. A method of treating heart failure in a mammal which method comprises administering to a mammal in need thereof a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising said compound or a pharmaceutically acceptable salt thereof.
4. The method of claim 3 wherein the heart failure is congestive heart failure.
5. The method of claim 3 wherein the heart failure is systolic heart failure.
6. A compound that is methyl 4-[(4-fluoro-3{ L (6-ethyl′3-pyridyl))amino]carbonylamino}phenyl)-methyl]piperazinecarboxylate
or a pharmaceutically acceptable salt thereof.
7. A pharmaceutical composition comprising a pharmaceutically acceptable excipient, carrier or adjuvant and a compound of claim 6 , or a pharmaceutically acceptable salt thereof.
8. A method of treating heart failure in a mammal which method comprises administering to a mammal in need thereof a therapeutically effective amount of a compound of claim 6 , or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising said compound or a pharmaceutically acceptable salt thereof.
9. The method of claim 8 wherein the heart failure is congestive heart failure.
10. The method of claim 8 wherein the heart failure is systolic heart failure.
11. A compound that is methyl 4-[(2-fluoro-3-{[(6-methyl(3-pyridyl))amino]carbonylamino}-phenyl)methyl]piperazinecarboxylate
or a pharmaceutically acceptable salt thereof.
12. A pharmaceutical composition comprising a pharmaceutically acceptable excipient, carrier or adjuvant and a compound of claim 11 , or a pharmaceutically acceptable salt thereof.
13. A method of treating heart failure in a mammal which method comprises administering to a mammal in need thereof a therapeutically effective amount of a compound of claim 11 , or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising said compound or a pharmaceutically acceptable salt thereof.
14. The method of claim 13 wherein the heart failure is congestive heart failure.
15. The method of claim 13 wherein the heart failure is systolic heart failure.
16. A compound that is methyl 4-[(3-{[(6-methyl-3-pyridyl)amino]carbonylamino}phenyl)-methyl]piperazinecarboxylate
or a pharmaceutically acceptable salt thereof.
17. A pharmaceutical composition comprising a pharmaceutically acceptable excipient, carrier or adjuvant and a compound of claim 16 , or a pharmaceutically acceptable salt thereof.
18. A method of treating heart failure in a mammal which method comprises administering to a mammal in need thereof a therapeutically effective amount of a compound of claim 16 , or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising said compound or a pharmaceutically acceptable salt thereof.
19. The method of claim 18 wherein the heart failure is congestive heart failure.
20. The method of claim 18 wherein the heart failure is systolic heart failure.
21. A compound that is methyl 4-[(1S)-1-(5-fluoro-3-{[(6-methyl(3-pyridyl))amino]carbonylamino}-phenyl)ethyl]piperazinecarboxylate
or a pharmaceutically acceptable salt thereof.
22. A pharmaceutical composition comprising a pharmaceutically acceptable excipient, carrier or adjuvant and a compound of claim 21 , or a pharmaceutically acceptable salt thereof.
23. A method of treating heart failure in a mammal which method comprises administering to a mammal in need thereof a therapeutically effective amount of a compound of claim 21 , or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising said compound or a pharmaceutically acceptable salt thereof.
24. The method of claim 23 wherein the heart failure is congestive heart failure.
25. The method of claim 23 wherein the heart failure is systolic heart failure.
26. A compound that is N-{3-[(1S)-1-(4-acetylpiperazinyl)ethyl]-2-fluorophenyl}[(6-methyl(3-pyridyl))amino]carboxamide
or a pharmaceutically acceptable salt thereof.
27. A pharmaceutical composition comprising a pharmaceutically acceptable excipient, carrier or adjuvant and a compound of claim 26 , or a pharmaceutically acceptable salt thereof.
28. A method of treating heart failure in a mammal which method comprises administering to a mammal in need thereof a therapeutically effective amount of a compound of claim 26 , or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising said compound or a pharmaceutically acceptable salt thereof.
29. The method of claim 28 wherein the heart failure is congestive heart failure.
30. The method of claim 28 wherein the heart failure is systolic heart failure.