Certain chemical entities, 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 method of increasing systolic ejection time in a subject, the method comprising administering to the subject a compound of formula
or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the extent but not the velocity of cardiac contraction is increased.
3. The method of claim 1 , wherein the extent of contraction but not +/−dP/dt is increased.
4. The method of claim 1 , wherein the compound is administered intravenously.
5. The method of claim 4 , wherein the compound is administered in an aqueous solution, wherein the aqueous solution further comprises citric acid.
6. The method of claim 1 , wherein the compound is administered orally.
7. A method of treating heart failure in a subject, the method comprising administering to the subject a compound of the formula
or a pharmaceutically acceptable salt thereof, wherein systolic ejection time is increased in the subject.
8. The method of claim 7 , wherein the extent but not the velocity of cardiac contraction is increased.
9. The method of claim 7 , wherein the extent of contraction but not +/−dP/dt is increased.
10. The method of claim 7 , wherein the compound is administered intravenously.
11. The method of claim 10 , wherein the compound is administered in an aqueous solution, wherein the aqueous solution further comprises citric acid.
12. The method of claim 1 , wherein the compound is administered orally.