Pyridoxal analogues and methods of treatment

1. A compound of the founula:

or a pharmaceutically acceptable acid addition salt thereof; wherein

R 1 is alkoxy;

dialkylamino;

alkanoyloxy;

alkanoyloxyaryl;

alkoxyalkanoyl;

alkoxycarbonyl;

dialkylcarbamoyloxy; or

aryl,

aryloxy,

arylthio, or

arakyl,

in which aryl can be substituted by alkyl, alkoxy, amino, hydroxy, halo, nitro, or alkanoyloxy.

2. A compound according to claim 1 , wherein R 1 is phenyl or naphthyl in which phenyl or naphthyl is unsubstituted or substituted by one or more groups of C 1-4 alkyl, C 1-4 alkoxy, amino, hydroxy, halo, nitro, or C 1-4 alkanoyloxy.

3. A compound according to claim 1 , wherein R 1 is (2-acetoxy-2-methyl)propanyl, dimethylamino, or 1-ethanoyloxy-1-methylethyl.

4. A compound according to claim 1 , wherein R 1 is methoxy or ethoxy.

5. A compound according to claim 1 , wherein R 1 is toluyl, naphthyl, phenyl, acetylphenyl, or 1-ethanoyloxyphenyl.

6. A compound according to claim 1 , wherein R 1 is acetylsalicyl, dimethylamino, or 2,2-dimethylethyl.

7. The compound of claim 1 that is 2-methyl-3-toluoyloxy-4-formyl-5-hydroxymethylpyridine.

8. The compound of claim 1 that is 2-methyl-3-β-naphthoyloxy-4-formyl-5-hydroxymethylpyridine.

9. A pharmaceutical composition comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound according to claim 1 .

10. A pharmaceutical composition of claim 9 , wherein the pharmaceutical composition is in a form suitable for enteral or parenteral administration.

11. A pharmaceutical composition of claim 9 , wherein the compound is 2-methyl-3-toluoyloxy-4-formyl-5-hydroxymethylpyridine, 2-methyl-3-β-naphthoyloxy-4-formyl-5-hydroxymethylpyridine, or a pharmaceutically acceptable acid addition salt thereof.

12. A method of treating cardiovascular and related diseases comprising: administering to the mammal a therapeutically effective amount of a compound of the formula:

or a pharmaceutically acceptable acid addition salt thereof in a unit dosage form, wherein

R 1 is C 1 -C 8 alkyl,

alkenyl,

in which alkyl or alkenyl

can be interrupted by nitrogen, oxygen, or sulfur, and

can be substituted at the terminal carbon by hydroxy, alkoxy; alkanoyloxy, alkanoyloxyaryl, alkoxyalkanoyl, alkoxycarbonyl, or dialkylcarbamoyloxy;

alkoxy;

dialkylamino;

alkanoyloxy;

alkanoyloxyaryl;

alkoxyalkanoyl;

allkoxycarbonyl;

dialkylcarbamoyloxy; or

aryl,

aryloxy,

arylthio, or

aralkyl,

in which aryl can be substituted by alkyl, alkoxy, amino, hydroxy, halo, nitro, or alkanoyloxy.

13. The method of claim 12 , wherein the compound is administered enterally or parenterally.

14. The method of claim 12 , wherein the disease is hypertension.

15. The method of claim 14 , wherein the compound is administered concurrently with a therapeutic cardiovascular compound selected from the group consisting of an angiotensin converting enzyme inhibitor, a calcium channel blocker, a β-adrenergic receptor antagonist, a vasodilator, a diuretic, an α-adrenergic receptor antagonist, and a mixture thereof.

16. The method of claim 12 , wherein the disease is myocardial infarction.

17. The method of claim 16 , wherein the compound is administered concurrently with a therapeutic cardiovascular compound selected from the group consisting of an angiotensin converting enzyme inhibitor, a calcium channel blocker, an antithromblytic agent, a β-adrenergic receptor antagonist, a diuretic, an α-adrenergic receptor antagonist, and a mixture thereof.

18. The method of claim 12 , wherein the disease is isehemia reperfusion injury.

19. The method of claim 18 , wherein the compound is administered concurrently with a therapeutic cardiovascular compound selected from the group consisting of an angiotensin converting enzyme inhibitor, an angiotensin II receptor antagonist, a calcium channel blocker, and a mixture thereof.

20. The method of claim 12 , wherein the disease is myocardial ischemia.

21. The method of claim 20 , wherein the compound is administered concurrently with a therapeutic cardiovascular compound selected from the group consisting of an angiotensin converting enzyme inhibitor, an angiotensin II receptor antagonist, a calcium channel blocker, an antithrombolytic agent, a β-adrenergic receptor antagonist, a diuretic, an α-adrenergic receptor antagonist, and a mixture thereof.

22. The method of claim 12 , wherein the disease is congestive heart failure.

23. The method of claim 22 , wherein the compound is administered concurrently with a therapeutic cardiovascular compound selected from the group consisting of an angiotensin converting enzyme inhibitor, an angiotensin II receptor antagonist, a calcium channel blocker, a vasodilator, a diuretic, and a mixture thereof.

24. The method of claim 12 , wherein the disease is arrhythmia.

25. The method of claim 24 , wherein the compound is administered concurrently with a therapeutic cardiovascular compound selected from the group consisting of a calcium channel blocker, a β-adrenergic receptor antagonist, and a mixture thereof.

26. The method of claim 12 , wherein the disease is blood coagulation.

27. The method of claim 26 , wherein the compound is administered concurrently with an antithrombolytic agent.

28. The method of claim 12 , wherein the disease is hypertrophy.

29. The method of claim 28 , wherein the compound is administered concurrently with a therapeutic cardiovascular compound selected from the group consisting of an angiotensin converting enzyme inhibitor, an angiotensin II receptor antagonist, a calcium channel blocker, and a mixture thereof.

30. The method of claim 12 , wherein the disease arises from thrombotic and prothrombotic states in which the coagulation cascade is activated.

31. The method of claim 30 , wherein the disease comprises deep vein thrombosis.

32. The method of claim 30 , wherein the disease comprises disseminated intravascular coagulopathy.

33. The method of claim 30 , wherein the disease comprises pulmonary embolism.

34. The method of claim 12 , wherein the disease is platelet aggregation.