Claims
- 1. A compound of formula (I)
- 2. The compound of claim 1, wherein R1, R2 and R3 are hydrogen atoms.
- 3. The compound of claim 1, wherein n=1 and R1 is selected from the group consisting of a methyl group, a methoxy group, a halogen and a nitro group.
- 4. The compound of claim 3, wherein the halogen is chlorine or bromine.
- 5. The compound of claim 1, wherein m=1 and R2 is a chlorine atom.
- 6. The compound of claim 1, wherein p and s=0.
- 7. The compound of claim 1, wherein Ar is selected from the group consisting of phenyl, furanyl, thiophenyl, pyridinyl, and thiazolyl.
- 8. The compound of claim 1, wherein R4 is a hydroxyl group.
- 9. The compound of claim 1, wherein R4 is proline, attached to the compound through its nitrogen atom.
- 10. The compound of claim 1, wherein the compound is selected from the group consisting of
3-(3-Chloro-biphenyl-4-yloxymethyl)-benzoic acid; 3-(Biphenyl-3-yloxymethyl)-benzoic acid; 3-(4′-Methyl-biphenyl-4-yloxymethyl)-benzoic acid; 3-(4′-Bromo-biphenyl-4-yloxymethyl)-benzoic acid; 3-(4′-Chloro-biphenyl-4-yloxymethyl)-benzoic acid; 3-(2′-Nitro-biphenyl-4-yloxymethyl)-benzoic acid; 3-(4′-Methoxy-biphenyl-4-yloxymethyl)-benzoic acid; 2-(3-Chloro-biphenyl-4-yloxymethyl)-benzoic acid; 2-(4′-Methyl-biphenyl-4-yloxymethyl)-benzoic acid; 2-(2′-Nitro-biphenyl-4-yloxymethyl)-benzoic acid; and 2-(Biphenyl-4-yloxymethyl)-benzoic acid.
- 11. The compound of claim 1, wherein the compound is selected from the group consisting of
5-(3-Chloro-biphenyl-4-yloxymethyl)-furan-2-carboxylic acid; 5-(Biphenyl-3-yloxymethyl)-furan-2-carboxylic acid; 5-(4′-Methyl-biphenyl-4-yloxymethyl)-furan-2-carboxylic acid; 5-(4′-Bromo-biphenyl-4-yloxymethyl)-furan-2-carboxylic acid; 5-(4′-Chloro-biphenyl-4-yloxymethyl)-furan-2-carboxylic acid; 5-(2′-Nitro-biphenyl-4-yloxymethyl)-furan-2-carboxylic acid; and 5-(4′-Nitro-biphenyl-4-yloxymethyl)-furan-2-carboxylic acid.
- 12. The compound of claim 1, wherein the compound is 5-(2′-Nitro-biphenyl-4-yloxymethyl)-thiophene-2-carboxylic acid.
- 13. The compound of claim 1, wherein the compound is selected from the group consisting of
6-(2′-Nitro-biphenyl-4-yloxymethyl)-pyridine-2-carboxylic acid; and 6-(Biphenyl-4-yloxymethyl)-pyridine-2-carboxylic acid.
- 14. The compound of claim 1, wherein the compound is selected from the group consisting of
2-(3-Chloro-biphenyl-4-yloxymethyl)-thiazole-4-carboxylic acid; 2-(Biphenyl-3-yloxymethyl)-thiazole-4-carboxylic acid; 2-(4′-Methyl-biphenyl-4-yloxymethyl)-thiazole-4-carboxylic acid; 2-(4′-Bromo-biphenyl-4-yloxymethyl)-thiazole-4-carboxylic acid; 2-(4′-Chloro-biphenyl-4-yloxymethyl)-thiazole-4-carboxylic acid; 2-(2′-Nitro-biphenyl-4-yloxymethyl)-thiazole-4-carboxylic acid; 2-(4′-Methoxy-biphenyl-4-yloxymethyl)-thiazole-4-carboxylic acid; 2-(Biphenyl-4-yloxymethyl)-thiazole-4-carboxylic acid; 4-(4′-Chloro-biphenyl-4-yloxymethyl)-thiazole-2-carboxylic acid; and 4-(Biphenyl-4-yloxymethyl)-thiazole-2-carboxylic acid.
- 15. The compound of claim 1, wherein the compound is selected from the group consisting of
1-[5-(Biphenyl-4-yloxymethyl)-furan-2-carbonyl]-D-pyrrolidine-2-carboxylic acid; (rac)-1-[5-(Biphenyl-4-yloxymethyl)-furan-2-carbonyl]-piperidine-2-carboxylic acid; and 1-{[5-(Biphenyl-4-yloxymethyl)-furan-2-carbonyl]-amino}-cyclopentanecarboxylic acid.
- 16. A method for treating or preventing a disease mediated by the activation of the glycogen synthase enzyme, comprising administering to a patient in need thereof, a therapeutically effective amount of a compound of the following formula (Ia)
- 17. A method for treating or preventing diabetes, comprising administering to a patient in need thereof, a therapeutically effective amount of a compound of the following formula (Ia)
- 18. The method of claim 17, wherein R1, R2 and R3 are hydrogen atoms.
- 19. The method of claim 17, wherein n=1 and R1 is selected from the group consisting of a methyl group, a methoxy group, a halogen and a nitro group.
- 20. The method of claim 19, wherein the halogen is chlorine or bromine.
- 21. The method of claim 17, wherein m=1 and R2 is a chlorine atom.
- 22. The method of claim 17, wherein p and s=0.
- 23. The method of claim 17, wherein Ar is selected from the group consisting of phenyl, furanyl, thiophenyl, pyridinyl, and thiazolyl.
- 24. The method of claim 17, wherein R4 is a hydroxyl group.
- 25. The method of claim 17, wherein R4 is proline, attached to the compound through its nitrogen atom.
- 26. The method of claim 17, wherein the compound is selected from the group consisting of
3-(3-Chloro-biphenyl-4-yloxymethyl)-benzoic acid; 3-(Biphenyl-3-yloxymethyl)-benzoic acid; 3-(4′-Methyl-biphenyl-4-yloxymethyl)-benzoic acid; 3-(4′-Bromo-biphenyl-4-yloxymethyl)-benzoic acid; 3-(4′-Chloro-biphenyl-4-yloxymethyl)-benzoic acid; 3-(2′-Nitro-biphenyl-4-yloxymethyl)-benzoic acid; 3-(4′-Methoxy-biphenyl-4-yloxymethyl)-benzoic acid; 3-(Biphenyl-4- yloxymethyl)-benzoic acid; 2-(3-Chloro-biphenyl-4-yloxymethyl)-benzoic acid; 2-(4′-Methyl-biphenyl-4-yloxymethyl)-benzoic acid; 2-(2′-Nitro-biphenyl-4-yloxymethyl)-benzoic acid; and 2-(Biphenyl-4-yloxymethyl)- benzoic acid.
- 27. The method of claim 17, wherein the compound is selected from the group consisting of
5-(3-Chloro-biphenyl-4-yloxymethyl)-furan-2-carboxylic acid; 5-(Biphenyl-3-yloxymethyl)-furan-2-carboxylic acid; 5-(4′-Methyl-biphenyl-4-yloxymethyl)-furan-2-carboxylic acid; 5-(4′-Bromo-biphenyl-4-yloxymethyl)-furan-2-carboxylic acid; 5-(4′-Chloro-biphenyl-4-yloxymethyl)-furan-2-carboxylic acid; 5-(2′-Nitro-biphenyl-4-yloxymethyl)-furan-2-carboxylic acid; 5-(4′-Nitro-biphenyl-4-yloxymethyl)-furan-2-carboxylic acid; and 5-(Biphenyl-4-yloxymethyl)-furan-2-carboxylic acid.
- 28. The method of claim 17, wherein the compound is selected from the group consisting of
5-(2′-Nitro-biphenyl-4-yloxymethyl)-thiophene-2-carboxylic acid; 5-(Biphenyl-4-yloxymethyl)-thiophene-2-carboxylic acid.
- 29. The method of claim 17, wherein the compound is selected from the group consisting of
6-(2′-Nitro-biphenyl-4-yloxymethyl)-pyridine-2-carboxylic acid; and 6-(Biphenyl-4-yloxymethyl)-pyridine-2-carboxylic acid.
- 30. The method of claim 17, wherein the compound is selected from the group consisting of
2-(3-Chloro-biphenyl-4-yloxymethyl)-thiazole-4-carboxylic acid; 2-(Biphenyl-3-yloxymethyl)-thiazole-4-carboxylic acid; 2-(4′-Methyl-biphenyl-4-yloxymethyl)-thiazole-4-carboxylic acid; 2-(4′-Bromo-biphenyl-4-yloxymethyl)-thiazole-4-carboxylic acid; 2-(4′-Chloro-biphenyl-4-yloxymethyl)-thiazole-4-carboxylic acid; 2-(2′-Nitro-biphenyl-4-yloxymethyl)-thiazole-4-carboxylic acid; 2-(4′-Methoxy-biphenyl-4-yloxymethyl)-thiazole-4-carboxylic acid; 2-(Biphenyl-4-yloxymethyl)-thiazole-4-carboxylic acid; 4-(4′-Chloro-biphenyl-4-yloxymethyl)-thiazole-2-carboxylic acid; and 4-(Biphenyl-4-yloxymethyl)-thiazole-2-carboxylic acid.
- 31. A pharmaceutical composition comprising a compound of formula(1a)
- 32. The pharmaceutical composition of claim 31, wherein R1, R2 and R3 are hydrogen atoms.
- 33. The pharmaceutical composition of claim 31, wherein n=1 and R1 is selected from the group consisting of a methyl group, a methoxy group, a halogen and a nitro group.
- 34. The pharmaceutical composition of claim 31, wherein the halogen is chlorine or bromine.
- 35. The pharmaceutical composition of claim 31, wherein m=1 and R2 is a chlorine atom.
- 36. The pharmaceutical composition of claim 31, wherein p and s=0.
- 37. The pharmaceutical composition of claim 31, wherein Ar is selected from the group consisting of phenyl, furanyl, thiophenyl, pyridinyl, and thiazolyl.
- 38. The pharmaceutical composition of claim 31, wherein R4 is a hydroxyl group.
- 39. The pharmaceutical composition of claim 31, wherein R4 is proline, attached to the compound through its nitrogen atom.
- 40. The pharmaceutical composition of claim 31, wherein the compound is selected from the group consisting of
3-(3-Chloro-biphenyl-4-yloxymethyl)-benzoic acid; 3-(Biphenyl-3-yloxymethyl)-benzoic acid; 3-(4′-Methyl-biphenyl-4-yloxymethyl)-benzoic acid; 3-(4′-Bromo-biphenyl-4-yloxymethyl)-benzoic acid; 3-(4′-Chloro-biphenyl-4-yloxymethyl)-benzoic acid; 3-(2′-Nitro-biphenyl-4-yloxymethyl)-benzoic acid; 3-(4′-Methoxy-biphenyl-4-yloxymethyl)-benzoic acid; 3-(Biphenyl-4-yloxymethyl)-benzoic acid; 2-(3-Chloro-biphenyl-4-yloxymethyl)-benzoic acid; 2-(4′-Methyl-biphenyl-4-yloxymethyl)-benzoic acid; 2-(2′-Nitro-biphenyl-4-yloxymethyl)-benzoic acid; and 2-(Biphenyl-4-yloxymethyl)-benzoic acid.
- 41. The pharmaceutical composition of claim 31, wherein the compound is selected from the group consisting of
5-(3-Chloro-biphenyl-4-yloxymethyl)-furan-2-carboxylic acid; 5-(Biphenyl-3-yloxymethyl)-furan-2-carboxylic acid; 5-(4′-Methyl-biphenyl-4-yloxymethyl)-furan-2-carboxylic acid; 5-(4′-Bromo-biphenyl-4-yloxymethyl)-furan-2-carboxylic acid; 5-(4′-Chloro-biphenyl-4-yloxymethyl)-furan-2-carboxylic acid; 5-(2′-Nitro-biphenyl-4-yloxymethyl)-furan-2-carboxylic acid; 5-(4′-Nitro-biphenyl-4-yloxymethyl)-furan-2-carboxylic acid; and 5-(Biphenyl-4-yloxymethyl)-furan-2-carboxylic acid.
- 42. The pharmaceutical composition of claim 31, wherein the compound is selected from the group consisting of
5-(2′-Nitro-biphenyl-4-yloxymethyl)-thiophene-2-carboxylic acid; 5-(Biphenyl-4-yloxymethyl)-thiophene-2-carboxylic acid.
- 43. The method of claim 31, wherein the compound is selected from the group consisting of
6-(2′-Nitro-biphenyl-4-yloxymethyl)-pyridine-2-carboxylic acid; and 6-(Biphenyl-4-yloxymethyl)-pyridine-2-carboxylic acid.
- 44. The pharmaceutical composition of claim 31, wherein the compound is selected from the group consisting of
2-(3-Chloro-biphenyl-4-yloxymethyl)-thiazole-4-carboxylic acid; 2-(Biphenyl-3-yloxymethyl)-thiazole-4-carboxylic acid; 2-(4′-Methyl-biphenyl-4-yloxymethyl)-thiazole-4-carboxylic acid; 2-(4′-Bromo-biphenyl-4-yloxymethyl)-thiazole-4-carboxylic acid; 2-(4′-Chloro-biphenyl-4-yloxymethyl)-thiazole-4-carboxylic acid; 2-(2′-Nitro-biphenyl-4-yloxymethyl)-thiazole-4-carboxylic acid; 2-(4′-Methoxy-biphenyl-4-yloxymethyl)-thiazole-4-carboxylic acid; 2-(Biphenyl-4-yloxymethyl)-thiazole-4-carboxylic acid; 4-(4′-Chloro-biphenyl-4-yloxymethyl)-thiazole-2-carboxylic acid; and 4-(Biphenyl-4-yloxymethyl)-thiazole-2-carboxylic acid.
- 45. The pharmaceutical composition of claim 31, wherein the compound is selected from the group consisting of
1-[5-(Biphenyl-4-yloxymethyl)-furan-2-carbonyl]-L-pyrrolidine-2-carboxylic acid; 1-[5-(Biphenyl-4-yloxymethyl)-furan-2-carbonyl]-D-pyrrolidine-2-carboxylic acid; (rac)-1-[5-(Biphenyl-4-yloxymethyl)-furan-2-carbonyl]-piperidine-2-carboxylic acid; and 1-{[5-(Biphenyl-4-yloxymethyl)-furan-2-carbonyl]-amino}-cyclopentanecarboxylic acid.
Priority to Provisional Application(s) Under 35 U.S.C. § 119(e)
[0001] This application claims priority under 35 U.S.C.§ 119(e) of Provisional Application Serial Nos. 60/480,900 filed Jun. 24, 2003; 60/482,147 filed June 24, 2003 and 60/569,356 filed May 7, 2004.
Provisional Applications (3)
|
Number |
Date |
Country |
|
60480900 |
Jun 2003 |
US |
|
60482147 |
Jun 2003 |
US |
|
60569356 |
May 2004 |
US |