Compounds for treatment of cardiac arrhythmia and methods of use

1. A pharmaceutically acceptable salt of a compound of structural Formula II:

wherein

R 1 is H or C 1 -C 10 alkyl;

R 2 is H or optionally substituted C 1 -C 10 alkyl, heteroalkyl, cycloalkyl or heterocycloalkyl;

n=0 to 4;

p=0 or 1;

R 3 and R 4 are, independently, H or C 1 -C 4 alkyl, and wherein the salt is selected from hydrochloride, hydrobromide, p-toluenesulfonate, phosphate, sulfate, perchlorate, acetate, trifluororacetate, propionate, citrate, malonate, succinate, lactate, oxalate, (L)-tartrate, (D)-tartrate, meso-tartrate, benzoate, alkali metal, morpholine, piperidine, dimethylamine, and diethylamine salts.

2. The salt according to claim 1 wherein

R 1 is H or ethyl;

R 2 is (S)-2-butyl, (R)-2-butyl, (S)-3-methyl-2-butyl or (R)-3-methyl-2-butyl;

n=0 or 1;

p=0; and

R 3 and R 4 are, independently, H or methyl.

3. The salt according to claim 2 wherein R 1 is ethyl.

4. The salt according to claim 2 wherein n is 1.

5. The salt according to claim 2 wherein R 1 is ethyl and n is 1.

6. The salt according to claim 1 wherein the compound is selected from:

7. The salt according to claim 1 wherein the compound is selected from:

a) (S)-{3-[4-(2-Ethylamino-ethoxy)-3,5-diiodo-benzoyl]-benzofuran-2-yl}-acetic acid sec-butyl ester;

b) {3-[4-(2-Ethylamino-ethoxy)-3,5-diiodo-benzoyl]-benzofiiran-2-yl}-acetic acid;

c) (S)-{3-[4-(2-Amino-ethoxy)-3,5-diiodo-benzoyl]-benzofuran-2-yl}-acetic acid sec-butyl ester;

d) {3-[4-(2-Amino-ethoxy)-3,5-diiodo-benzoyl]-benzofuran-2-yl}-acetic acid;

e) (R)-{3-[4-(2-Ethylamino-ethoxy)-3,5-diiodo-benzoyl]-benzofuran-2-yl}-acetic acid sec-butyl ester;

f) (R)-{3-[4-(2-Amino-ethoxy)-3,5-diiodo-benzoyl]benzofuran-2-yl}-acetic acid sec-butyl ester;

g) (S)-{3-[4-(2-Ethylamino-ethoxy)-3,5-diiodo-benzoyl]benzofuran-2-yl}-acetic acid 1,2-dimethyl-propyl ester;

h) (R)-{3-[4-(2-Ethylamino-ethoxy)-3,5-diiodo-benzoyl]-benzofuran-2-yl}-acetic acid 1,2-dimethyl-propyl ester;

i) (S)-{3-[4-(2-Amino-ethoxy)-3,5-diiodo-benzoyl]benzofuran-2-yl}-acetic acid 1,2-dimethyl-propyl ester; and

j) (R)-{3-[4-(2-Amino-ethoxy)-3,5-diiodobenzoyl]benzofuran-2-yl}-acetic acid 1,2-dimethyl-propyl ester.

8. A composition comprising a salt according to claim 1 and a pharmaceutically acceptable carrier, diluent, or excipient.

9. A composition comprising a salt according to claim 2 and a pharmaceutically acceptable carrier, diluent, or excipient.

10. A composition comprising a salt according to claim 3 and a pharmaceutically acceptable carrier, diluent, or excipient.

11. A composition comprising a salt according to claim 4 and a pharmaceutically acceptable carrier, diluent, or excipient.

12. A composition comprising a salt according to claim 5 and a pharmaceutically acceptable carrier, diluent, or excipient.

13. A composition comprising a salt according to claim 6 and a pharmaceutically acceptable carrier, diluent, or excipient.

14. A composition comprising a salt according to claim 7 and a pharmaceutically acceptable carrier, diluent, or excipient.

15. A compound of structural Formula II:

or a pharmaceutically acceptable salt thereof, wherein

R 1 is H or C 1 -C 10 alkyl;

R 2 is H or optionally substituted C 1 -C 10 alkyl, heteroalkyl, cycloalkyl or heterocycloalkyl;

n=0 to 4;

p=0 or 1;

R 3 and R 4 are, independently, H or C 1 -C 4 alkyl;

and wherein a compound contains less than 20% impurities on a weight basis.

16. A compound according to claim 15 wherein a compound contains less than 10% impurities.

17. A compound according to claim 16 wherein a compound contains less than 5% impurities.

18. The compound according to claim 15 wherein

R 1 is H or ethyl;

R 2 is (S)-2-butyl, (R)-2-butyl, (S)-3-methyl-2-butyl or (R)-3-methyl-2-butyl;

n=0 or 1;

p=0; and

R 3 and R 4 are, independently, H or methyl.

19. A compound according to claim 18 wherein a compound contains less than 10% impurities.

20. A compound according to claim 19 wherein a compound contains less than 5% impurities.

21. The compound according to claim 18 wherein R 1 is ethyl.

22. A compound according to claim 21 wherein a compound contains less than 10% impurities.

23. A compound according to claim 22 wherein a compound contains less than 5% impurities.

24. The compound according to claim 18 wherein n is 1.

25. A compound according to claim 24 wherein a compound contains less than 10% impurities.

26. A compound according to claim 25 wherein a compound contains less than 5% impurities.

27. A compound according to claim 18 wherein R 1 is ethyl and n is 1.

28. A compound according to claim 27 wherein a compound contains less than 10% impurities.

29. A compound according to claim 28 wherein a compound contains less than 5% impurities.

30. The compound according to claim 15 wherein the compound is selected from:

31. A compound according to claim 30 wherein a compound contains less than 10% impurities.

32. A compound according to claim 31 wherein a compound contains less than 5% impurities.

33. The compound according to claim 15 wherein the compound is selected from:

a) (S)-{3-[4-(2-Ethylamino-ethoxy)-3,5-diiodo-benzoyl]-benzofuran-2-yl}-acetic acid sec-butyl ester;

b) {3-[4-(2-Ethylamino-ethoxy)-3,5-diiodo-benzoyl]-benzofuran-2-yl}-acetic acid;

c) (S)-{3-[4-(2-Amino-ethoxy)-3,5-diiodo-benzoyl]-benzofuran-2-yl}1-acetic acid sec-butyl ester;

d) {3-[4-(2-Amino-ethoxy)-3,5-diiodo-benzoyl]-benzofuran-2-yl}-acetic acid;

e) (R)-{3-[4-(2-Ethylamino-ethoxy)-3,5-diiodo-benzoyl]-benzofuran-2-yl}-acetic acid sec-butyl ester;

f) (R)-{3-[4-(2-Amino-ethoxy)-3,5-diiodo-benzoyl]benzofuran-2-yl}-acetic acid sec-butyl ester;

g) (S)-{3-[4-(2-Ethylamino-ethoxy)-3,5-diiodo-benzoyl]benzofuran-2-yl}-acetic acid 1,2-dimethyl-propyl ester;

h) (R)-{3-[4-(2-Ethylamino-ethoxy)-3,5-diiodo-benzoyl]-benzofuran-2-yl}-acetic acid 1,2-dimethyl-propyl ester;

i) (S)-{(3-[4-(2-Amino-ethoxy)-3,5-diiodo-benzoyl]benzofuran-2-yl}-acetic acid 1,2-dimethyl-propyl ester; and

j) (R)-{3-[4-(2-Amino-ethoxy)-3,5-diiodobenzoyl]benzofuran-2-yl}-acetic acid 1,2-dimethyl-propyl ester.

34. A compound according to claim 33 wherein a compound contains less than 10% impurities.

35. A compound according to claim 34 wherein a compound contains less than 5% impurities.

36. A composition comprising a compound according to claim 16 and a pharmaceutically acceptable carrier, diluent, or excipient.

37. A composition comprising a compound according to claim 19 and a pharmaceutically acceptable carrier, diluent, or excipient.

38. A composition comprising a compound according to claim 22 and a pharmaceutically acceptable carrier, diluent, or excipient.

39. A composition comprising a compound according to claim 25 and a pharmaceutically acceptable carrier, diluent, or excipient.

40. A composition comprising a compound according to claim 28 and a pharmaceutically acceptable carrier, diluent, or excipient.

41. A composition comprising a compound according to claim 31 and a pharmaceutically acceptable carrier, diluent, or excipient.

42. A composition comprising a compound according to claim 34 and a pharmaceutically acceptable carrier, diluent, or excipient.