Pyridoxal analogues and methods of treatment
View Patent ↗Pyridoxal analogues can be useful for treating B 6 deficiency and related diseases; cardiovascular and related diseases; melanoma and related diseases; and symptoms thereof. One such analogue is a compound of the formula: or a pharmaceutically acceptable acid addition salt thereof, in which R 1 is 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; alkoxycarbonyl; dialkylcarbamoyloxy; or aryl, aryloxy, arylthio, or aralkyl, in which aryl can be substituted by alkyl, alkoxy, amino, hydroxy, halo, nito, or alkanoyloxy. These analogues can be administered, either alone or concurrently with known medications, to treat the above-described diseases.
1. A composition comprising a compound of formula VI
wherein
R 1 is 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;
alkoxycarbonyl;
dialkylcarbamoyloxy; or
aryl, in which aryl can be substituted by alkyl, alkoxy, amino, hydroxy, halo, nitro, or alkanoyloxy
aryloxy,
arylthio, or
aralkyl; and
R 2 is of the formula
wherein R 3 and R 4 are each independently alkyl, alkenyl, cycloalkyl, aryl, or, when R 3 and R 4 are taken together to form a ring with the nitrogen atom, which may optionally be interrupted by a heteroatom, wherein said heteroatom is selected from the group consisting of nitrogen, sulfur, and oxygen,
or a pharmaceutically acceptable acid addition salt thereof;
an angiotensin converting enzyme inhibitor, pyridoxal phosphate-6-azophenyl-2′,4′-disulphonic acid, or a mixture thereof, wherein said angiotensin converting enzyme inhibitor is selected from the group consisting of: captopril, enalapril, lisinopril, benazapril, fosinopril, quinapril, ramipril, spirapril, imidapril, moexipril, and combinations thereof; and
a therapeutically acceptable carrier.
2. A composition 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 composition according to claim 1 , wherein R 1 is (2-acetoxy-2-methyl)propanyl, dimethylamino, or 1-ethanoyloxy-1-methylethyl.
4. A composition according to claim 1 , wherein R 1 is tert-butyl.
5. A composition according to claim 1 , wherein R 1 is methoxy or ethoxy.
6. A composition according to claim 1 , wherein R 1 is toluyl, naphthyl, phenyl, acetylphenyl, or 1-ethanoyloxyphenyl.
7. A composition according to claim 1 , wherein R 1 is acetylsalicyl, dimethylamino, or 2,2-dimethylethyl.
8. A composition according to claim 1 , wherein said compound is 2-methyl-3-toluoyloxy-4-formyl-5-hydroxymethylpyridine.
9. A composition according to claim 1 , wherein said compound is 2-methyl-3-β-naphthoyloxy-4-formyl-5-hydroxymethylpyridine.
10. A composition of claim 1 , wherein said R 2 of the formula
is selected from the group consisting of dimethylamino, methylethylamino, diethylamino, dialkylamino, phenylmethylamino, and diphenylamino.
11. A composition of claim 1 , wherein R 2 is selected from the group consisting of piperazino and morpholino.