IP Library › Granted Patent US 6,897,228
Granted Patent B2
US 6,897,228 · App. 10/411,552 · Granted May 24, 2005

Pyridoxine and pyridoxal analogues: new uses

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Quick Facts
Patent No.
US 6,897,228
App. No.
10/411,552
Granted
May 24, 2005
Kind
B2
Abstract

The invention provides pyridoxal and pyridoxine analogues, pharmaceutical compositions containing pyridoxine and pyridoxal analogues, and methods of administering pharmaceutical compositions containing a therapeutically effective amount of at least one of these analogues. In accordance with the present invention, the pyridoxal and pyridoxine analogues can be used in the treatment or prevention of of heparin induced thrombocytopenia (HIT, stroke, and ischemia, and in the treatment of symptoms thereof. The the pyridoxal and pyridoxine analogues can be used in neuroprotection.

Claims (100)

1. A method of treating heparin induced thrombocytopenia (HIT), in a mammalian patient comprising administering a therapeutically effective amount of a compound of Formula V:

or a pharmaceutically acceptable acid addition salt thereof, wherein:

R 5 is CH 2 OH or CHO;

R 1 is

n is an integer of 1 to 5;

R 2 , R 3 , and R 4 are each independently

hydrogen;

alkyl;

aryl or biaryl,

wherein the aryl or biaryl can be substituted with a cyano, alkyl, alkoxy, amino, hydroxy, halo, nitro, or alkanoyloxy;

amino;

acylamino;

anilino,

wherein the aniline ring can be substituted with a cyano, alkyl, alkoxy, amino, hydroxy, halo, nitro, or alkanoyloxy;

nitro; or

guanidino.

2. The method of claim 1 wherein said compound is administered to induce a plasma level of said compound of between about 100 nM and 10,000 μM.

3. The method of claim 2 wherein said plasma level is between 200 μM and 4000 μM.

4. The method of claim 3 wherein said plasma level is between 500 μM and 2000 μM.

5. The method of claim 1 wherein said therapeutically effective dose is between about 0.1 to 100 mg/kg body weight per day.

6. The method of claim 5 wherein said compound is administered intravenously, orally, sublingually, intraperitoneally, transdermally, intramuscularly or subcutaneously.

7. The method of claim 1 wherein said compound is administered intravenously.

8. The method of claim 1 wherein said compound is administered orally.

9. The method of claim 1 wherein the compound is

10. The method of claim 3 wherein the compound is

11. A method of treating stroke in a mammalian patient comprising administering a therapeutically effective amount of a compound of Formula V:

or a pharmaceutically acceptable acid addition salt thereof, wherein:

R 5 is CH 2 OH or CHO;

R 1 is

n is an integer of 1 to 5;

R 2 , R 3 , and R 4 are each independently

hydrogen;

alkyl;

aryl or biaryl,

wherein the aryl or biaryl can be substituted with a cyano, alkyl, alkoxy, amino, hydroxy, halo, nitro, or alkanoyloxy;

amino;

acylamino;

anilino,

wherein the aniline ring can be substituted with a cyano, alkyl, alkoxy, amino, hydroxy, halo, nitro, or alkanoyloxy;

nitro; or

guanidino.

12. The method of claim 11 wherein said compound is administered to induce a plasma level of said compound of between about 100 nM and 10,000 μM.

13. The method of claim 11 wherein said therapeutically effective dose is between about 0.1 to 100 mg/kg body weight per day.

14. The method of claim 13 wherein said dosage is between 1 mg/kg and 100 mg/kg body weight.

15. The method of claim 14 wherein said dosage is between 5 mg/kg and 80 mg/kg body weight.

16. The method of claim 13 wherein said compound is administered intravenously, orally, sublingually, intraperitoneally, transdermally, intramuscularly or subcutaneously.

17. The method of claim 11 wherein said compound is administered intravenously.

18. The method of claim 11 wherein said compound is administered orally.

19. The method of claim 11 wherein the compound is

20. The method of claim 13 wherein the compound is

21. A method of treating ischemia in a mammalian patient comprising administering a therapeutically effective amount of a compound of Formula V:

or a pharmaceutically acceptable acid addition salt thereof, wherein:

R 5 is CH 2 OH or CHO;

R 1 is

n is an integer of 1 to 5;

R 2 , R 3 , and R 4 are each independently

hydrogen;

alkyl;

aryl or biaryl,

wherein the aryl or biaryl can be substituted with a cyano, alkyl, alkoxy, amino, hydroxy, halo, nitro, or alkanoyloxy;

amino;

acylamino;

anilino;

wherein the aniline ring can be substituted with a cyano, alkyl, alkoxy, amino, hydroxy, halo, nitro, or alkanoyloxy;

nitro; or

guanidino.

22. The method of claim 21 wherein said compound is administered to induce a plasma level of said compound of between about 100 nM and 10,000 μM.

23. The method of claim 21 wherein said therapeutically effective dose is between about 0.1 to 100 mg/kg body weight per day.

24. The method of claim 23 wherein said dosage is between 1 mg/kg and 100 mg/kg body weight.

25. The method of claim 24 wherein said dosage is between 5 mg/kg and 80 mg/kg body weight.

26. The method of claim 23 wherein said compound is administered intravenously, orally, sublingually, intraperitoneally, transdermally, intramuscularly or subcutaneously.

27. The method of claim 21 wherein said compound is administered intravenously.

28. The method of claim 21 wherein said compound is administered orally.

29. The method of claim 21 wherein the compound is

30. The method of claim 23 wherein the compound is

31. A method of providing a neuroprotective effect in a mammalian patient comprising administering a therapeutically effective amount of a compound of Formula V:

or a pharmaceutically acceptable acid addition salt thereof, wherein:

R 5 is CH 2 OH or CHO;

R 1 is

n is an integer of 1 to 5;

R 2 , R 3 , and R 4 are each independently

hydrogen;

alkyl;

aryl or biaryl,

wherein the aryl or biaryl can be substituted with a cyano, alkyl, alkoxy, amino, hydroxy, halo, nitro, or alkanoyloxy;

amino;

acylamino;

anilino,

wherein the aniline ring can be substituted with a cyano, alkyl, alkoxy, amino, hydroxy, halo, nitro, or alkanoyloxy;

nitro; or

guanidino.

32. The method of claim 31 wherein said compound is administered to in a dosage of between 0.1 mg/kg and 100 mg/kg.

33. The method of claim 32 wherein said dosage is between 1 mg/kg and 100 mg/kg.

34. The method of claim 33 wherein said plasma level is between 5 mg/kg and 80 mg/kg.

35. The method of claim 31 wherein said compound is administered to induce a plasma level of said compound of between about 100 nM and 10,000 μM.

36. The method of claim 33 wherein said compound is administered intravenously, orally, sublingually, intraperitoneally, transdermally, intramuscularly or subcutaneously.

37. The method of claim 31 wherein said compound is administered intravenously.

38. The method of claim 31 wherein said compound is administered orally.

39. The method of claim 31 wherein the compound is

40. The method of claim 33 wherein the compound is