Treatment of diabetes
The present invention relates to methods and compounds for regulating glucose metabolism, achieving glucose homeostasis, and decreasing blood glucose levels. Methods and compounds for treating or preventing diabetes, hyperglycemia, and disorders and conditions associated with altered or impaired glucose metabolism are also provided.
1. A method for treating diabetes in a diabetic subject, the method comprising administering to the subject an effective amount of a heterocyclic carbonyl glycine compound which inhibits a hypoxia inducible factor (HIF) hydroxylase, thereby treating diabetes in the subject.
2. A method for treating hyperglycemia in a hyperglycemic subject, the method comprising administering to the subject an effective amount of a heterocyclic carbonyl glycine compound which inhibits a HIF hydroxylase, thereby treating hyperglycemia in the subject.
3. A method for decreasing blood glucose levels in a diabetic or hyperglycemic subject, the method comprising administering to the subject an effective amount of a heterocyclic carbonyl glycine compound which inhibits a HIF hydroxylase, thereby decreasing blood glucose levels in the subject.
4. The method of any one of claims 1 , 2 , and 3 , wherein the HIF hydroxylase is a HIF prolyl hydroxylase.
5. The method of any one of claims 1 , 2 , and 3 , wherein the subject is a mammal.
6. The method of claim 5 , wherein the mammal is a human.
7. The method of any one of claims 1 , 2 , and 3 , wherein the compound is [(7-Chloro-3-hydroxy-quinoline-2-carbonyl)-amino]-acetic acid.
8. The method of any one of claims 1 , 2 , and 3 , wherein the compound is [(1-Chloro-4-hydroxy-isoquinoline-3-carbonyl)-amino]-acetic acid.
9. The method of any one of claims 1 , 2 , and 3 , wherein the compound is [(4-Hydroxy-7-phenoxy-isoquinoline-3-carbonyl)-amino]-acetic acid.
10. The method of any one of claims 1 , 2 , and 3 , wherein the compound is [(1-Chloro-4-hydroxy-7-methoxy-isoquinoline-3-carbonyl)-amino]-acetic acid.
11. The method of any one of claims 1 , 2 , and 3 , wherein the compound is [(3-Hydroxy-6-isopropoxy-quinoline-2-carbonyl)-amino]-acetic acid.
12. The method of any one of claims 1 , 2 , and 3 , wherein the compound is [(3-Hydroxy-pyridine-2-carbonyl)-amino]-acetic acid.
13. The method of any one of claims 1 , 2 , and 3 , wherein the compound is [(7-Benzyloxy-1-chloro-4-hydroxy-isoquinoline-3-carbonyl)-amino]-acetic acid methyl ester.
14. The method of claim 4 , wherein the HIF prolyl hydroxylase is selected from the group consisting of EGLN1, EGLN2, and EGLN3.
15. The method of any one of claims 1 , 2 , and 3 , wherein the heterocyclic carbonyl glycine is a substituted quinoline-2-carboxamide or esters thereof; a substituted isoquinoline-3-carboxamide or esters thereof; a 3-methoxy pyridine carbonyl glycine or esters thereof; a 3-hydroxypyridine carbonyl glycine or esters thereof; or a 5-sulfonamideocarbonyl pyridine carboxylate or esters thereof.