Cardioprotective phosphonates and malonates
View Patent ↗The present invention provides for pyridoxine phosphonate analogues such as, for example, ((2-methyl-3-hydroxy-4-hydroxymethyl-5-pyridyl)alkylphosphonates, and (2-methyl-3-hydroxy-4-hydroxymethyl-5-pyridyl)azaalkylphosphonates) and to pyridoxine malonate analogues, such as, for example, ((2-methyl-3-hydroxy-4-hydroxymethyl-5-pyridylmethyl)malonates), pharmaceutical compositions, and methods for treatment of cardiovascular and related diseases, and diabetes mellitus and related diseases.
1. A compound of the formula I
in which
R 1 is hydrogen or alkyl;
R 2 is CHO,
R 3 is hydrogen and R 4 is hydroxy, halo, alkoxy, alkylcarbonyloxy, alkylamino or arylamino; and
R 5 is hydrogen, alkyl, aryl, aralkyl, or —CO 2 R 7 in which R 7 is hydrogen, alkyl, aryl, or aralkyl;
or a pharmaceutically acceptable acid addition salt thereof.
2. A compound according to claim 1 , wherein R 1 is hydrogen.
3. A compound according to claim 1 , wherein R 3 is hydrogen and R 4 is F, MeO—, or CH 3 C(O)O—.
4. A compound according to claim 1 , wherein R 5 is alkyl or aralkyl.
5. A compound according to claim 4 , wherein R 5 is t-butyl or benzyl.
6. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound according to claim 1 .
7. A pharmaceutical composition of claim 6 , wherein the pharmaceutical composition is in a form suitable for enteral or parenteral administration.
8. A method of treating hypertension in a mammal comprising administering to the mammal a therapeutically effective amount of a compound according to claim 1 in a unit dosage form.
9. The method of claim 8 , wherein the compound is administered enterally or parenterally.
10. A method of treating myocardial infarction, ischemia reperfusion injury, myocardial ischemia, congestive heart failure, or arrhythmia in a mammal comprising administering to the mammal a therapeutically effective amount of a compound according to claim 1 in a unit dosage form.
11. The method of claim 10 , wherein the compound is administered enterally or parenterally.