5-deutero-2,4-thiazolidinedione derivatives and compositions comprising and methods of using the same
The invention provides 5-deuterium-enriched 2,4-thiazolidinediones (e.g., 5-[4-[2-(5-ethyl-2-pyridyl)-2-oxoethoxy]benzyl]-5-deutero-thiazolidine-2,4-dione), deuterated derivatives thereof, stereoisomers thereof, pharmaceutically acceptable salt forms thereof, and methods of treatment using the same.
1. A deuterium-enriched compound represented by:
or a stereoisomer or pharmaceutically acceptable salt form thereof; wherein Z is H or D, provided that the abundance of deuterium in Z is at least 30%.
2. The deuterium-enriched compound of claim 1 , wherein the compound is
or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein Z is H or D, provided that the abundance of deuterium in Z is at least 50%.
3. The deuterium-enriched compound of claim 1 , wherein the compound is
or a stereoisomer thereof, wherein Z is H or D, provided that the abundance of deuterium in Z is at least 50%.
4. The deuterium-enriched compound of claim 2 , wherein the abundance of deuterium in Z is at least 80%.
5. The deuterium-enriched compound of claim 2 , wherein the abundance of deuterium in Z is at least 90%.
6. The deuterium-enriched compound of claim 2 , wherein the abundance of deuterium in Z is at least 95%.
7. The deuterium-enriched compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt form thereof, wherein the compound has an enantiomeric excess, with respect to the C—Z carbon, of at least 80%, and Z is H or D, provided that the abundance of deuterium in Z is at least 50%.
8. The deuterium-enriched compound of claim 1 , wherein the compound is
wherein the compound has an enantiomeric excess, with respect to the C—Z carbon, of at least 80%, and Z is H or D, provided that the abundance of deuterium in Z is at least 50%.
9. The deuterium-enriched compound of claim 7 , wherein the abundance of deuterium in Z is at least 80%.
10. The deuterium-enriched compound of claim 7 , wherein the abundance of deuterium in Z is at least 90%.
11. The deuterium-enriched compound of claim 7 , wherein the abundance of deuterium in Z is at least 95%.
12. The deuterium-enriched compound of claim 10 , wherein the compound has an enantiomeric excess, with respect to the C—Z carbon, of at least 90%.
13. The deuterium-enriched compound of claim 11 , wherein the compound has an enantiomeric excess, with respect to the C—Z carbon, of at least 95%.
14. The deuterium-enriched compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt form thereof, wherein the compound has an enantiomeric excess, with respect to the C—Z carbon, of at least 80%, and Z is H or D, provided that the abundance of deuterium in Z is at least 50%.
15. The deuterium-enriched compound of claim 1 , wherein the compound is
wherein the compound has an enantiomeric excess, with respect to the C—Z carbon, of at least 80%, and Z is H or D, provided that the abundance of deuterium in Z is at least 50%.
16. The deuterium-enriched compound of claim 14 , wherein the abundance of deuterium in Z is at least 80%.
17. The deuterium-enriched compound of claim 14 , wherein the abundance of deuterium in Z is at least 90%.
18. The deuterium-enriched compound of claim 14 , wherein the abundance of deuterium in Z is at least 95%.
19. The deuterium-enriched compound of claim 17 , wherein the compound has an enantiomeric excess, with respect to the C—Z carbon, of at least 90%.
20. The deuterium-enriched compound of claim 18 , wherein the compound has an enantiomeric excess, with respect to the C—Z carbon, of at least 95%.
21. The deuterium-enriched compound of claim 1 wherein the abundance of deuterium in Z is at least 80%.
22. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and a compound of claim 1 .
23. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and a compound of claim 2 .
24. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and a compound of claim 7 .
25. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and a compound of claim 14 .
26. A method of treating a metabolic inflammation mediated disease selected from the group consisting of Type I diabetes, Type II diabetes, insulin resistance, and inadequate glucose tolerance, comprising administering to a patient in need thereof a therapeutically effective amount a compound of claim 1 to treat the disease.
27. The method of claim 26 , wherein the disease is Type II diabetes.
28. The method of claim 26 , wherein the compound is a compound of claim 2 .
29. The method of claim 27 , wherein the compound is a compound of claim 2 .
30. The method of claim 26 , wherein the compound is a compound of claim 7 .
31. The method of claim 26 , wherein the compound is a compound of claim 14 .