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 of formula VI 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%;
R A is C 1-4 alkoxy.
2. The deuterium-enriched compound of claim 1 , wherein the compound is of formula Via or Vib, or a pharmaceutically acceptable salt form thereof:
wherein the compound has an enantiomeric excess, with respect to the C—Z carbon, of at least 5%.
3. A The deuterium-enriched compound having the formula:
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%.
4. The deuterium-enriched compound of claim 3 , 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 5%.
5. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and a compound of claim 3 .
6. 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 of a compound of claim 3 to treat the disease.
7. The method of claim 6 , wherein the disease is Type II diabetes.
8. The deuterium-enriched compound of claim 3 , wherein the abundance of deuterium in Z is at least 90%.
9. The deuterium-enriched compound of claim 3 , wherein the abundance of deuterium in Z is at least 95%.
10. The deuterium-enriched compound of claim 4 , 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%.
11. The deuterium-enriched compound of claim 10 , wherein the abundance of deuterium in Z is at least 90%.
12. The deuterium-enriched compound of claim 10 , wherein the abundance of deuterium in Z is at least 95%.
13. The deuterium-enriched compound of claim 10 , wherein the abundance of deuterium in Z is at least 97%.
14. The deuterium-enriched compound of claim 11 , wherein the compound has an enantiomeric excess, with respect to the C—Z carbon, of at least 90%.
15. 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%.
16. The deuterium-enriched compound of claim 12 , wherein the compound has an enantiomeric excess, with respect to the C—Z carbon, of at least 95%.
17. The deuterium-enriched compound of claim 12 , wherein the compound has an enantiomeric excess, with respect to the C—Z carbon, of at least 98%.
18. The deuterium-enriched compound of claim 13 , wherein the compound has an enantiomeric excess, with respect to the C—Z carbon, of at least 98%.
19. The deuterium-enriched compound of claim 4 , 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%.
20. The deuterium-enriched compound of claim 19 , wherein the abundance of deuterium in Z is at least 90%.
21. The deuterium-enriched compound of claim 19 , wherein the abundance of deuterium in Z is at least 95%.
22. The deuterium-enriched compound of claim 19 , wherein the abundance of deuterium in Z is at least 97%.
23. The deuterium-enriched compound of claim 20 , wherein the compound has an enantiomeric excess, with respect to the C—Z carbon, of at least 90%.
24. The deuterium-enriched compound of claim 20 , wherein the compound has an enantiomeric excess, with respect to the C—Z carbon, of at least 95%.
25. The deuterium-enriched compound of claim 21 , wherein the compound has an enantiomeric excess, with respect to the C—Z carbon, of at least 95%.
26. The deuterium-enriched compound of claim 21 , wherein the compound has an enantiomeric excess, with respect to the C—Z carbon, of at least 98%.
27. The deuterium-enriched compound of claim 22 , wherein the compound has an enantiomeric excess, with respect to the C—Z carbon, of at least 98%.
28. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and a deuterium-enriched compound of claim 11 .
29. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and a deuterium-enriched compound of claim 16 .
30. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and a deuterium-enriched compound of claim 20 .
31. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and a deuterium-enriched compound of claim 25 .
32. The method of claim 6 , wherein the compound is a compound of claim 16 .
33. The method of claim 6 , wherein the compound is a compound of claim 25 .
34. The method of claim 7 , wherein the compound is a compound of claim 16 .
35. The method of claim 7 , wherein the compound is a compound of claim 25 .