Treatment of Diabetes and Related Pathologies
Methods for treating diabetes mellitus and related conditions and symptoms are described. The methods are directed to administering a therapeutically effective amount of a compound. Compounds suitable for the invention include pyridoxal-5′-phosphate, pyridoxal, pyridoxamine, pyridoxine, a 3-acylated pyridoxal analogue, a pharmaceutically acceptable acid addition salt thereof, or a mixture thereof. Also disclosed are methods directed to concurrently administering a therapeutically effective amount of a compound with other compounds known in the treatment of diabetes mellitus. In one embodiment, a therapeutically effective amount of a compound is administered concurrently with a therapeutically effective amount of insulin. In another embodiment, a therapeutically effective amount of a compound is administered concurrently with a therapeutically effective amount of a hypoglycemic compound.
1 - 27 . (canceled)
28 . A method of treating insulin resistance in a mammal comprising: administering to the mammal a therapeutically effective amount of a compound selected from the group consisting of pyridoxal-5′-phosphate, pyridoxamine, pyridoxal, a 3-acylated pyridoxal analogue, a pharmaceutically acceptable acid addition salt thereof, and a mixture thereof.
29 . A method according to claim 28 , wherein the 3-acylated pyridoxal analogue is a compound of the formula
wherein
R 1 is a straight or branched alkyl group, a straight or branched alkenyl group, in which an alkyl or alkenyl group may be interrupted by a nitrogen or oxygen atom; an alkoxy group; a dialkylamino group; or an unsubstituted or substituted aryl group.
30 . A method according to claim 28 , wherein the 3-acylated pyridoxal analogue is a compound of the formula
wherein
R 1 is a straight or branched alkyl group, a straight or branched alkenyl group, in which an alkyl or alkenyl group may be interrupted by a nitrogen or oxygen atom; an alkoxy group; a dialkylamino group; or an unsubstituted or substituted aryl group; 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; or
a pharmaceutically acceptable acid addition salt thereof.
31 . The method of claim 28 comprising: concurrently administering insulin with the compound.
32 . A method according to claim 31 , wherein the 3-acylated pyridoxal analogue is a compound of the formula
wherein
R 1 is a straight or branched alkyl group, a straight or branched alkenyl group, in which an alkyl or alkenyl group may be interrupted by a nitrogen or oxygen atom; an alkoxy group; a dialkylamino group; or an unsubstituted or substituted aryl group.
33 . A method according to claim 31 , wherein the 3-acylated pyridoxal analogue is a compound of the formula
wherein
R 1 is a straight or branched alkyl group, a straight or branched alkenyl group, in which an alkyl or alkenyl group may be interrupted by a nitrogen or oxygen atom; an alkoxy group; a dialkylamino group; or an unsubstituted or substituted aryl group; 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; or
a pharmaceutically acceptable acid addition salt thereof.
34 . The method of claim 28 comprising: concurrently administering a hypoglycemic compound with the compound selected.
35 . A method according to claim 34 , wherein the 3-acylated pyridoxal analogue is a compound of the formula
wherein
R 1 is a straight or branched alkyl group, a straight or branched alkenyl group, in which an alkyl or alkenyl group may be interrupted by a nitrogen or oxygen atom; an alkoxy group; a dialkylamino group; or an unsubstituted or substituted aryl group.
36 . A method according to claim 34 , wherein the 3-acylated pyridoxal analogue is a compound of the formula
wherein
R 1 is a straight or branched alkyl group, a straight or branched alkenyl group, in which an alkyl or alkenyl group may be interrupted by a nitrogen or oxygen atom; an alkoxy group; a dialkylamino group; or an unsubstituted or substituted aryl group; 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; or
a pharmaceutically acceptable acid addition salt thereof.
37 . A method according to claim 34 , wherein the hypoglycemic compound is acarbose, acetohexamide, chlorpropamide, glimepiride, glipizide, glyburide, metformin, tolazamide, tolbutamide, or a mixture thereof.
38 . A method according to claim 34 , wherein the hypoglycemic compound is tolbutamide.
39 . A method according to claim 34 further comprising:
concurrently administering to the mammal the compound and the hypoglycemic compound in combination with a therapeutically effective amount of insulin.
40 . A method of treating hyperinsulinemia in a mammal comprising: administering to the mammal a therapeutically effective amount of a compound selected from the group consisting of pyridoxal-5′-phosphate, pyridoxamine, pyridoxal, a 3-acylated pyridoxal analogue, a pharmaceutically acceptable acid addition salt thereof, and a mixture thereof,
wherein the 3-acylated pyridoxal analogue is a compound of the formula
wherein R 1 is a straight or branched alkyl group, a straight or branched alkenyl group, in which an alkyl or alkenyl group may be interrupted by a nitrogen or oxygen atom; an alkoxy group; a dialkylamino group; or an unsubstituted or substituted aryl group; and
wherein the 3-acylated pyridoxal analogue is a compound of the formula
wherein
R 1 is a straight or branched alkyl group, a straight or branched alkenyl group, in which an alkyl or alkenyl group may be interrupted by a nitrogen or oxygen atom; an alkoxy group; a dialkylamino group; or an unsubstituted or substituted aryl group; 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; or
a pharmaceutically acceptable acid addition salt thereof.
41 - 42 . (canceled)
43 . The method of claim 40 comprising: concurrently administering insulin with the compound.
44 - 45 . (canceled)
46 . The method of claim 43 comprising: concurrently administering hypoglycemic compound with the compound.
47 - 48 . (canceled)
49 . A method according to claim 46 , wherein the hypoglycemic compound is acarbose, acetohexamide, chlorpropamide, glimepiride, glipizide, glyburide, metformin, tolazamide, tolbutamide, or a mixture thereof.
50 . A method according to claim 46 , wherein the hypoglycemic compound is tolbutamide.
51 . A method according to claim 46 further comprising:
concurrently administering to the mammal the compound and the hypoglycemic compound in combination with a therapeutically effective amount of insulin.
52 - 75 . (canceled)