Claims
- 1. A compound of formula I, a prodrug thereof or a pharmaceutically acceptable salt of said compound or said prodrug, wherein:R is N,N-dimethylamino or isopropyl.
- 2. The compound of claim 1 of the formula
- 3. The compound of claim 1 of the formula
- 4. A pharmaceutical composition comprising a compound of claim 1, a prodrug thereof or a pharmaceutically acceptable salt of said compound or said prodrug and a pharmaceutically acceptable carrier or diluent.
- 5. A method of inhibiting sorbitol dehydrogenase in a mammal in need of such inhibition comprising administering to said mammal a sorbitol dehydrogenase inhibiting amount of a compound of claim 1, a prodrug thereof or a pharmaceutically acceptable salt of said prodrug or said compound.
- 6. A method of treating diabetes in a mammal suffering from diabetes comprising administering to said mammal an effective amount of a compound of claim 1, a prodrug thereof or a pharmaceutically acceptable salt of said prodrug or said compound.
- 7. A method of treating or preventing diabetic complications in a mammal comprising administering to said mammal an effective amount of a compound of claim 1, a prodrug thereof or a pharmaceutically acceptable salt of said prodrug or said compound.
- 8. A method of claim 7 wherein said mammal is suffering from diabetes.
- 9. A method of claim 8 wherein said diabetic complication is diabetic neuropathy.
- 10. A method of claim 8 wherein said diabetic complication is diabetic nephropathy.
- 11. A method of claim 8 wherein said diabetic complication is diabetic retinopathy.
- 12. A method of claim 8 wherein said diabetic complication is foot ulcers.
- 13. A method of claim 8 wherein said diabetic complication is a cardiovascular condition.
- 14. A pharmaceutical composition comprising a compound of claim 1, a prodrug thereof or a pharmaceutically acceptable salt of said prodrug or said compound, and an aldose reductase inhibitor (ARI), a prodrug of said ARI or a pharmaceutically acceptable salt of said ARI or said prodrug.
- 15. A composition of claim 14 additionally comprising a pharmaceutically acceptable carrier or diluent.
- 16. A method of treating diabetes in a mammal suffering from diabetes comprising administering to said mammal an effective amount of a compound of claim 1, a prodrug thereof or a pharmaceutically acceptable salt of said prodrug or said compound, and an aldose reductase inhibitor (ARI), a prodrug of said ARI or a pharmaceutically acceptable salt of said ARI or said prodrug.
- 17. A method of treating or preventing diabetic complications in a mammal comprising administering to said mammal an effective amount of a compound of claim 1, a prodrug thereof or a pharmaceutically acceptable salt of said prodrug or said compound, and an aldose reductase inhibitor (ARI), a prodrug of said ARI or a pharmaceutically acceptable salt of said ARI or said prodrug.
- 18. A method of claim 17 wherein said mammal is suffering from diabetes.
- 19. A method of claim 17 wherein said diabetic complication is diabetic neuropathy.
- 20. A method of claim 17 wherein said diabetic complication is diabetic nephropathy.
- 21. A method of claim 17 wherein said diabetic complication is diabetic retinopathy.
- 22. A method of claim 17 wherein said diabetic complication is foot ulcers.
- 23. A method of claim 17 wherein said diabetic complication is a cardiovascular condition.
- 24. A pharmaceutical composition comprising a compound of claim 1, a prodrug thereof or a pharmaceutically acceptable salt of said prodrug or said compound, and a sodium hydrogen ion exchange (NHE-1) inhibitor, a prodrug of said NHE-1 inhibitor or a pharmaceutically acceptable salt of said NHE-1 inhibitor or said prodrug.
- 25. A method of treating ischemia in a mammal suffering from ischemia comprising administering to said mammal an effective amount of a compound of claim 1, a prodrug thereof or a pharmaceutically acceptable salt of said prodrug or said compound, and a sodium hydrogen ion exchange (NHE-1) inhibitor, a prodrug of said NHE-1 inhibitor or a pharmaceutically acceptable salt of said NHE-1 inhibitor or said prodrug.
- 26. A method of claim 25 wherein said ischemia is perioperative myocardial ischemia.
- 27. A method of treating or preventing diabetic complications in a mammal comprising administering to said mammal an effective amount of a compound of claim 1, a prodrug thereof or a pharmaceutically acceptable salt of said prodrug or said compound, and a sodium hydrogen ion exchange (NHE-1) inhibitor, a prodrug of said NHE-1 inhibitor or a pharmaceutically acceptable salt of said NHE-1 inhibitor or said prodrug.
- 28. A method of claim 27 wherein said mammal is suffering from diabetes.
- 29. A method of claim 27 wherein said diabetic complication is diabetic neuropathy.
- 30. A method of claim 27 wherein said diabetic complication is diabetic nephropathy.
- 31. A method of claim 27 wherein said diabetic complication is diabetic retinopathy.
- 32. A method of claim 27 wherein said diabetic complication is foot ulcers.
- 33. A method of claim 27 wherein said diabetic complication is a cardiovascular condition.
- 34. A method of treating diabetes in a mammal suffering from diabetes comprising administering to said mammal an effective amount of a compound of claim 1, a prodrug thereof or a pharmaceutically acceptable salt of said prodrug or said compound, and a sodium hydrogen ion exchange (NHE-1) inhibitor, a prodrug of said NHE-1 inhibitor or a pharmaceutically acceptable salt of said NHE-1 inhibitor or said prodrug.
- 35. A kit comprising:a. a compound of claim 1, a prodrug thereof or a pharmaceutically acceptable salt of said prodrug or said compound in a first unit dosage form; b. an aldose reductase inhibitor, a prodrug thereof or a pharmaceutically acceptable salt of said prodrug or said aldose reductase inhibitor in a second unit dosage form; and c. a container.
- 36. A kit comprising:a. a compound of claim 1, a prodrug thereof or a pharmaceutically acceptable salt of said prodrug or said compound in a first unit dosage form; b. a sodium hydrogen ion exchange (NHE-1) inhibitor, a prodrug thereof or a pharmaceutically acceptable salt of said prodrug or said NHE-1 inhibitor in a second unit dosage form; and c. a container.
- 37. A method of inhibiting sorbitol dehydrogenase in a mammal in need thereof comprising administering to said mammal a pharmaceutical composition of claim 4.
- 38. A method of treating ischemia in a mammal suffering from ischemia comprising administering to said mammal a pharmaceutical composition of claim 24.
- 39. A method of treating or preventing diabetic complications in a mammal comprising administering to said mammal a pharmaceutical composition of claim 4.
- 40. A method of treating or preventing diabetic complications in a mammal comprising administering to said mammal a pharmaceutical composition of claim 14.
- 41. A method of treating or preventing diabetic complications in a mammal comprising administering to said mammal a pharmaceutical composition of claim 24.
- 42. A compound of the formula II, wherein:R is N,N-dimethylamino or isopropyl; and R1 is (C1-C4)alkyl, benzyl or phenyl, said benzyl and phenyl being optionally substituted with up to three (C1-C4)alkyl, (C1-C4)alkoxy, halo or nitro.
- 43. A compound of the formula III, wherein:R is N,N-dimethylamino or isopropyl; and R5 is
- 44. A compound of the formula IV:
- 45. A pharmaceutical composition comprising a compound of claim 1, a prodrug thereof or a pharmaceutically acceptable salt of said prodrug or said compound, and a glycogen phosphorylase inhibitor (GPI), a prodrug of said GPI or a pharmaceutically acceptable salt of said GPI or said prodrug.
- 46. A kit comprising:a. a compound of claim 1, a prodrug thereof or a pharmaceutically acceptable salt of said prodrug or said compound in a first unit dosage form; b. a glycogen phosphorylase inhibitor (GPI), a prodrug thereof or a pharmaceutically acceptable salt of said prodrug or said GPI in a second unit dosage form; and c. a container.
Parent Case Info
This application is filed claiming priority from co-pending Provisional Application No. 60/127,430 filed Apr. 1, 1999.
US Referenced Citations (4)
Number |
Name |
Date |
Kind |
5138058 |
Geisen et al. |
Aug 1992 |
|
5215990 |
Geisen et al. |
Jun 1993 |
|
5728704 |
Mylari et al. |
Mar 1998 |
|
5866578 |
Mylari et al. |
Feb 1999 |
|
Foreign Referenced Citations (1)
Number |
Date |
Country |
0384370 |
Aug 1990 |
EP |
Non-Patent Literature Citations (3)
Entry |
S. Ao et al., Metabolism, 40, 77-87, 1991. |
N. E. Cameron and M. A. Cotter, Diabetic Medicine, 8, Suppl. 1, 35A-36A, 1991. |
D. J. Brown, The Pyrimidines, 1962. |
Provisional Applications (1)
|
Number |
Date |
Country |
|
60/127430 |
Apr 1999 |
US |