Compositions and methods for treating heart failure

1. A method of potentiating cardiac myosin, which method comprises administering to a mammal in need thereof an amount of a compound represented by Formula I effective to potentiate cardiac myosin

wherein:

R 1 is alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl;

R 2 is acetyl, acetylamino, acetylene, alkoxycarbonyl, carboxamido, cyano, halo, heteroaryl, hydrogen, nitro or trifluoromethyl; and

R 3 is aryl, substituted aryl, heteroaryl or substituted heteroaryl;

or a single stereoisomer, or mixture of stereoisomers, or a pharmaceutically acceptable salt thereof,

wherein “substituted” alkyl, aryl, and heteroaryl refer respectively to alkyl, aryl, and heteroaryl wherein one to three hydrogen atoms are replaced by a substituent independently selected from alkyl, fluoroalkyl, alkoxy, cyano, halogen, hydroxy, and nitro.

2. The method of claim 1 where R 1 is phenyl, substituted phenyl or pyridinyl.

3. The method of claim 2 where R 1 is 3-chlorophenyl, 4-fluorophenyl, 4-hydroxyphenyl, 3-methylphenyl, pyridin-2-yl or pyridin-3-yl.

4. The method of claim 1 where R 2 is acetyl, acetylene, alkoxycarbonyl, cyano, halo, heteroaryl, hydrogen, nitro or trifluoromethyl.

5. The method of claim 4 where R 2 is acetylene, cyano, ethoxycarbonyl, fluoro, hydrogen, nitro, oxazol-2-yl, pyridin-2-yl, pyrimidin-2-yl, thiazol-2-yl or trifluoromethyl.

6. The method of claim 1 where R 3 is:

phenyl, optionally substituted with lower alkoxy, lower alkyl, halo, hydroxy, or nitro; or

furanyl, indolyl, isoxazolyl, pyrazolyl, pyridinyl or thiophen-2-yl, each of which is optionally substituted with lower alkyl, lower alkoxy, or halo.

7. The method of claim 6 where R 3 is 3-hydroxyphenyl, 4-hydroxyphenyl, 4-fluorophenyl, isoxazol-5-yl, pyridin-3-yl, pyridin-4-yl, thiophen-2-yl or 5-methyl-thiophen-2-yl.

8. The method of claim 1 where R 1 is substituted phenyl and R 2 is nitro.

9. The method of claim 8 where R 1 is 4-fluorophenyl.

10. The method of claim 1 where R 1 is heteroaryl and R 2 is fluoro.

11. The method of claim 10 where R 1 is pyridin-3-yl.

12. The method of claim 1 where R 1 is heteroaryl and R 2 is nitro.

13. The method of claim 12 where R 1 is pyridin-3-yl.

14. The method of claim 13 where R 3 is phenyl, 4-fluorophenyl, 4-cyanophenyl, 4-methoxyphenyl or 4-methylphenyl.

15. The method of claim 1 where the compound is:

N-[3-(4-fluoro-phenoxy)-(5-nitro-phenyl)]-isonicotinamide;

4-fluoro-N-[3-(pyridin-3-yloxy)-phenyl]-benzamide;

thiophene-2-carboxylic acid [3-(4-fluoro-phenoxy)-5-nitro-phenyl]-amide;

isoxazole-5-carboxylic acid [3-(4-fluoro-phenoxy)-5-nitro-phenyl]-amide;

N-[3-cyano-5-(pyridin-3-yloxy)-phenyl]-4-fluoro-benzamide;

4-fluoro-N-[3-(pyridin-3-yloxy)-5-trifluoromethyl-phenyl]-benzamide;

3-(4-fluoro-benzoylamino)-5-(pyridin-3-yloxy)-benzoic acid ethyl ester;

5-methyl-thiophene-2-carboxylic acid [3-nitro-5-(pyridin-3-yloxy)phenyl]-amide;

4-fluoro-N-[3-pyridin-2-yl-5-(pyridin-3-yloxy)-phenyl]-benzamide;

4-fluoro-N-[3-pyrazin-2-yl-5-(pyridin-3-yloxy)-phenyl]-benzamide;

4-fluoro-N-[3-nitro-5-(pyridin-2-yloxy)-phenyl]-benzamide;

N-[3-fluoro-5-(pyridin-3-yloxy)-phenyl]-3-hydroxy-benzamide;

N-[3-fluoro-5-(pyridin-3-yloxy)-phenyl]-4-hydroxy-benzamide;

N-[3-fluoro-5-(pyridin-3-yloxy)-phenyl]-nicotinamide; and

isoxazole-5-carboxylic acid [3-fluoro-5-(pyridin-3-yloxy)-phenyl]-amide.