US2003008847A1PendingUtilityA1
Treatment of diabetes and related pathologies
Est. expiryJul 13, 2019(expired)· nominal 20-yr term from priority
A61K 31/675A61K 31/64A61K 31/4415A61K 31/5375A61K 31/435A61K 31/44A61K 31/4355A61P 3/10A61K 31/715A61K 45/06
58
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
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.
Claims
exact text as granted — not AI-modifiedWe claim:
1 . A method of treating diabetes mellitus 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, pyidoxine, a 3-acylated pyridoxal analogue, a pharmaceutically acceptable acid addition salt thereof, and a mixture thereof.
2 . A method according to claim 1 , wherein the diabetes mellitus treated is insulin-dependent diabetes mellitus.
3 . A method according to claim 1 , wherein the diabetes mellitus treated is noninsulin-dependent diabetes mellitus.
4 . A method according to claim 1 , 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.
5 . A method according to claim 4 , wherein R 1 is phenyl or naphthyl in which phenyl or naphthyl is unsubstituted or substituted by an alkyl group of 1 to 4 carbon atoms, an alkoxy group of 1 to 4 carbon atoms, an amino group, a hydroxy group, or an acetyloxy group.
6 . A method according to claim 4 , wherein the 3-acylated pyridoxal analogue is 2-methyl-3-toluoyloxy-4-formyl-5-hydroxymethylpyridine.
7 . A method according to claim 4 , wherein the 3-acylated pyridoxal analogue is 2-methyl-3-β-naphthoyloxy-4-formyl-5-hydroxymethylpyridine.
8 . A method according to claim 1 , 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 a secondary amino group.
9 . A method according to claim 8 , wherein R 1 is an alkyl group; an alkoxy group; a dialkylamino group; or phenyl or naphthyl in which phenyl or naphthyl is unsubstituted or substituted by an alkyl group of 1 to 4 carbon atoms, an alkoxy group of 1 to 4 carbon atoms, an amino group, a hydroxy group, or an acetyloxy group.
10 . A method according to claim 8 , wherein R 2 is a group of the formula
wherein R 3 and R 4 are each independently alkyl or when taken together form a ring with the nitrogen atom and which ring may optionally be interrupted by a nitrogen or oxygen atom.
11 . A method according to claim 8 , wherein the 3-acylated pyridoxal analogue is 1-morpholino-1,3-dihydro-7-(p-toluoyloxy)-6-methylfuro(3,4-c)pyridine.
12 . A method according to claim 8 , wherein the 3-acylated pyridoxal analogue is 1-morpholino-1,3-dihydro-7-(β-naphthoyloxy)-6-methylfuro(3,4-c)pyridine.
13 . A method according to claim 8 , wherein the 3-acylated pyridoxal analogue is 1-morpholino-1,3-dihydro-7-pivaloyloxy-6-methylfuro(3,4-c)pyridine.
14 . A method according to claim 8 , wherein the 3-acylated pyridoxal analogue is 1-morpholino-1,3-dihydro-7-(dimethylcarbamoyloxy-6-methylfuro(3,4-c)pyridine.
15 . A method according to claim 8 , wherein the 3-acylated pyridoxal analogue is 1-morpholino-1,3-dihydro-7-acetylsalicyloxy-6-methylfuro(3,4-c)pyridine.
16 . A method according to claim 1 , wherein the compound is administered enterally or parenterally.
17 . A method according to claim 1 , wherein the therapeutically effective amount is in a range of about 0.5-100 mg/kg of the mammal's body weight per day.
18 . A method of treating diabetes mellitus in a mammal comprising: concurrently administering to the mammal a therapeutically effective amount of a combination of insulin and a compound selected from the group consisting of pyridoxal-5′-phosphate, pyridoxamine, pyridoxal, pyridoxine, a 3-acylated pyridoxal analogue, a pharmaceutically acceptable acid addition salt thereof, and a mixture thereof.
19 . A method according to claim 18 , wherein the diabetes mellitus treated is insulin-dependent diabetes mellitus.
20 . A method according to claim 18 , 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.
21 . A method according to claim 18 , 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 a secondary amino group.
22 . A method of treating noninsulin-dependent diabetes mellitus in a mammal comprising: concurrently administering to the mammal a therapeutically effective amount of a combination of a hypoglycemic compound and a compound selected from the group consisting of pyridoxal-5′-phosphate, pyridoxamine, pyridoxal, pyridoxine, a 3-acylated pyridoxal analogue, a pharmaceutically acceptable acid addition salt thereof, and a mixture thereof.
23 . A method according to claim 22 , 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.
24 . A method according to claim 22 , 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 a secondary amino group.
25 . A method according to claim 22 , wherein the hypoglycemic compound is acarbose, acetohexamide, chlorpropamide, glimepiride, glipizide, glyburide, metformin, tolazamide, tolbutamide, or a mixture thereof.
26 . A method according to claim 22 , wherein the hypoglycemic compound is tolbutamide.
27 . A method according to claim 22 further comprising:
concurrently administering to the mammal the compound and the hypoglycemic compound in combination with a therapeutically effective amount of insulin.
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, pyridoxine, 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 a secondary amino group.
31 . A method of treating insulin resistance in a mammal comprising: concurrently administering to the mammal a therapeutically effective amount of a combination of insulin and a compound selected from the group consisting of pyridoxal-5′-phosphate, pyridoxamine, pyridoxal, pyridoxine, a 3-acylated pyridoxal analogue, a pharmaceutically acceptable acid addition salt thereof, and a mixture thereof.
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 a secondary amino group.
34 . A method of treating insulin resistance in a mammal comprising: concurrently administering to the mammal a therapeutically effective amount of a combination of a hypoglycemic compound and a compound selected from the group consisting of pyridoxal-5′-phosphate, pyridoxamine, pyridoxal, pyridoxine, a 3-acylated pyridoxal analogue, a pharmaceutically acceptable acid addition salt thereof, and a mixture thereof.
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 a secondary amino group.
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, pyridoxine, a 3-acylated pyridoxal analogue, a pharmaceutically acceptable acid addition salt thereof, and a mixture thereof.
41 . A method according to claim 40 , 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.
42 . A method according to claim 40 , 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 a secondary amino group.
43 . A method of treating hyperinsulinemia in a mammal comprising: concurrently administering to the mammal a therapeutically effective amount of a combination of insulin and a compound selected from the group consisting of pyridoxal-5′-phosphate, pyridoxamine, pyridoxal, pyridoxine, a 3-acylated pyridoxal analogue, a pharmaceutically acceptable acid addition salt thereof, and a mixture thereof.
44 . A method according to claim 43 , 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.
45 . A method according to claim 43 , 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 a secondary amino group.
46 . A method of treating hyperinsulinemia in a mammal comprising: concurrently administering to the mammal a therapeutically effective amount of a combination of a hypoglycemic compound and a compound selected from the group consisting of pyridoxal-5′-phosphate, pyridoxamine, pyridoxal, pyridoxine, a 3-acylated pyridoxal analogue, a pharmaceutically acceptable acid addition salt thereof, and a mixture thereof.
47 . A method according to claim 46 , 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.
48 . A method according to claim 46 , 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 a secondary amino group.
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 . A method of treating diabetes-induced hypertension 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, pyridoxine, a 3-acylated pyridoxal analogue, a pharmaceutically acceptable acid addition salt thereof, and a mixture thereof.
53 . A method according to claim 52 , 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.
54 . A method according to claim 52 , 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 a secondary amino group.
55 . A method of treating diabetes-induced hypertension in a mammal comprising: concurrently administering to the mammal a therapeutically effective amount of a combination of insulin and a compound selected from the group consisting of pyridoxal-5′-phosphate, pyridoxamine, pyridoxal, pyridoxine, a 3-acylated pyridoxal analogue, a pharmaceutically acceptable acid addition salt thereof, and a mixture thereof.
56 . A method according to claim 55 , 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.
57 . A method according to claim 55 , 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 a secondary amino group.
58 . A method of treating diabetes-induced hypertension in a mammal comprising: concurrently administering to the mammal a therapeutically effective amount of a combination of a hypoglycemic compound and a compound selected from the group consisting of pyridoxal-5′-phosphate, pyridoxamine, pyridoxal, pyridoxine, a 3-acylated pyridoxal analogue, a pharmaceutically acceptable acid addition salt thereof, and a mixture thereof.
59 . A method according to claim 58 , 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.
60 . A method according to claim 58 , 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 a secondary amino group.
61 . A method according to claim 58 , wherein the hypoglycemic compound is acarbose, acetohexamide, chlorpropamide, glimepiride, glipizide, glyburide, metformin, tolazamide, tolbutamide, or a mixture thereof.
62 . A method according to claim 58 , wherein the hypoglycemic compound is tolbutamide.
63 . A method according to claim 58 further comprising:
concurrently administering to the mammal the compound and the hypoglycemic compound in combination with a therapeutically effective amount of insulin.
64 . A method of treating diabetes-related damage to blood vessels, eyes, kidneys, nerves, autonomic nervous system, skin, connective tissue, or immune system 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, pyridoxine, a 3-acylated pyridoxal analogue, a pharmaceutically acceptable acid addition salt thereof, and a mixture thereof.
65 . A method according to claim 64 , 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.
66 . A method according to claim 64 , 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 a secondary amino group.
67 . A method of treating diabetes-related damage to blood vessels, eyes, kidneys, nerves, autonomic nervous system, skin, connective tissue, or immune system in a mammal comprising: concurrently administering to the mammal a therapeutically effective amount of a combination of insulin and a compound selected from the group consisting of pyridoxal-5′-phosphate, pyridoxamine, pyridoxal, pyridoxine, a 3-acylated pyridoxal analogue, a pharmaceutically acceptable acid addition salt thereof, and a mixture thereof.
68 . A method according to claim 67 , 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.
69 . A method according to claim 67 , 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 a secondary amino group.
70 . A method of treating diabetes-related damage to blood vessels, eyes, kidneys, nerves, autonomic nervous system, skin, connective tissue, or immune system in a mammal comprising: concurrently administering to the mammal a therapeutically effective amount of a combination of a hypoglycemic compound and a compound selected from the group consisting of pyridoxal-5′-phosphate, pyridoxamine, pyridoxal, pyridoxine, a 3-acylated pyridoxal analogue, a pharmaceutically acceptable acid addition salt thereof, and a mixture thereof.
71 . A method according to claim 70 , 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.
72 . A method according to claim 70 , 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 a secondary amino group.
73 . A method according to claim 70 , wherein the hypoglycemic compound is acarbose, acetohexamide, chlorpropamide, glimepiride, glipizide, glyburide, metformin, tolazamide, tolbutamide, or a mixture thereof.
74 . A method according to claim 70 , wherein the hypoglycemic compound is tolbutamide.
75 . A method according to claim 70 further comprising:
concurrently administering to the mammal the compound and the hypoglycemic compound in combination with a therapeutically effective amount of insulin.Join the waitlist — get patent alerts
Track US2003008847A1 — get alerts on status changes and closely related new filings.
We store only your email — no account needed. See our privacy policy.