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 formula V or a stereoisomer or pharmaceutically acceptable salt form thereof:
wherein:
R 10 is H or D;
Z is H or D, provided that the abundance of deuterium in Z is at least 30%;
R A is selected from: H, halo, C 1-4 alkyl optionally substituted with 1 halo, and C 1-4 alkoxy optionally substituted with 1 halo; and
R 11 is selected from: OH and OD.
2. The deuterium-enriched compound of claim 1 , wherein the compound is a compound of formula Va or Vb 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. The deuterium-enriched compound of claim 1 , wherein the compound is a compound of formula Vc, Vd, Ve, or Vf or a pharmaceutically acceptable salt form thereof:
wherein the compound has a stereomeric purity of at least 5%.
4. The deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in Z is selected from: (f) at least 90%, (g) at least 95%, (h) at least 97%, and (i) about 100%.
5. The deuterium-enriched compound of claim 2 , wherein the enantiomeric excess, with respect to the C—Z carbon, is selected from: (h) at least 80%, (i) at least 90%, (j) at least 95%, (k) at least 97%, (l) at least 98%, and (m) at least 99%.
6. The deuterium-enriched compound of claim 2 , wherein the enantiomeric excess, with respect to the C—Z carbon, is at least 90%.
7. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and a compound of claim 1 .
8. 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 1 to treat the disease.
9. A method of treating nonalcoholic steatohepatitis (NASH), comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 .