5-DEUTERO-THIAZOLIDINE-2,4-DIONE COMPOUNDS AND METHODS OF TREATING MEDICAL DISORDERS USING SAME

1 . A compound represented by Formula I:

or a pharmaceutically acceptable salt thereof, wherein:

Z is H or D, provided that the abundance of deuterium in Z is at least 30%;

A 1 is one of the following:

R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , and R 26 are independently H or D; and

the compound has a stereochemical purity of at least 75% enantiomeric excess at the carbon atom bearing variable Z.

2 . The compound of claim 1 , wherein the compound is one of the following:

(i) a compound of Formula I-A:

or a pharmaceutically acceptable salt thereof, wherein:

Z is H or D, provided that the abundance of deuterium in Z is at least 30%;

R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , and R 16 are independently H or D; and

the compound has an enantiomeric excess of at least 75%;

(ii) a compound of Formula I-B:

or a pharmaceutically acceptable salt thereof, wherein:

Z is H or D, provided that the abundance of deuterium in Z is at least 30%;

R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 0 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 and R 22 are independently H or D; and

the compound has an enantiomeric excess of at least 75%;

(iii) a compound of Formula I-C:

or a pharmaceutically acceptable salt thereof, wherein:

Z is H or D, provided that the abundance of deuterium in Z is at least 30%;

R 1 , R 2 , R 1 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 0 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , and R 19 are independently H or D; and

the compound has an enantiomeric excess of at least 75%; or

(iv) a compound of Formula I-D:

or a pharmaceutically acceptable salt thereof, wherein:

Z is H or D, provided that the abundance of deuterium in Z is at least 30%;

R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 1 , R 9 , R 10 , R 11 , R 2 , R 13 , R 14 , R 15 , R 16 , R 17 , and R 18 are independently H or D; and

the compound has a stereochemical purity of at least 75% enantiomeric excess at the carbon atom bearing variable Z.

3 . (canceled)

4 . The compound of claim 1 , wherein the compound is one of the following:

having a stereochemical purity of at least 85% enantiomeric excess, or a pharmaceutically acceptable salt thereof;

having a stereochemical purity of at least 85% enantiomeric excess, or a pharmaceutically acceptable salt thereof;

having a stereochemical purity of at least 85% enantiomeric excess, or a pharmaceutically acceptable salt thereof; or

having a stereochemical purity of at least 85% enantiomeric excess at the carbon atom bearing variable Z, or a pharmaceutically acceptable salt thereof.

5 - 17 . (canceled)

18 . The compound of claim 1 , wherein the compound is a compound of Formula I-E:

or a pharmaceutically acceptable salt thereof, wherein:

Z is H or D, provided that the abundance of deuterium in Z is at least 30%;

R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 0 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , and R 23 are independently H or D; and

the compound has an enantiomeric excess of at least 75%.

19 . The compound of claim 18 , wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , and R 23 are H.

20 . The compound of claim 18 , wherein the compound is

having a stereochemical purity of at least 85% enantiomeric excess, or a pharmaceutically acceptable salt thereof.

21 . The compound of claim 18 , wherein the compound is

having a stereochemical purity of at least 90% enantiomeric excess, or a pharmaceutically acceptable salt thereof.

22 . The compound of claim 1 , wherein the compound is one of the following:

(i) a compound of Formula I-F:

or a pharmaceutically acceptable salt thereof, wherein:

Z is H or D, provided that the abundance of deuterium in Z is at least 30%;

R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , and R 16 are independently H or D; and

the compound has an enantiomeric excess of at least 75%;

(ii) a compound of Formula I-G:

or a pharmaceutically acceptable salt thereof, wherein:

Z is H or D, provided that the abundance of deuterium in Z is at least 30%;

R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , and R 15 are independently H or D; and

the compound has an enantiomeric excess of at least 75%;

(iii) a compound of Formula I-H:

or a pharmaceutically acceptable salt thereof, wherein:

Z is H or D, provided that the abundance of deuterium in Z is at least 30%;

R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 0 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 and R 18 are independently H or D; and

the compound has an enantiomeric excess of at least 75%; or

(iv) a compound of Formula I-I:

or a pharmaceutically acceptable salt thereof, wherein:

Z is H or D, provided that the abundance of deuterium in Z is at least 30%;

R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 0 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , and R 26 are independently H or D; and

the compound has a stereochemical purity of at least 75% enantiomeric excess at the carbon atom bearing variable Z.

23 . (canceled)

24 . The compound of claim 22 , wherein the compound is one of the following:

having a stereochemical purity of at least 85% enantiomeric excess, or a pharmaceutically acceptable salt thereof;

having a stereochemical purity of at least 85% enantiomeric excess, or a pharmaceutically acceptable salt thereof;

having a stereochemical purity of at least 85% enantiomeric excess, or a pharmaceutically acceptable salt thereof; or

having a stereochemical purity of at least 85% enantiomeric excess at the carbon atom bearing variable Z, or a pharmaceutically acceptable salt thereof.

25 - 39 . (canceled)

40 . The compound of claim 18 , wherein the abundance of deuterium in Z is at least 90%.

41 . (canceled)

42 . The compound of claim 18 , wherein the compound has a stereochemical purity of at least 90% enantiomeric excess.

43 . The compound of claim 18 , wherein the compound has a stereochemical purity of at least 95% enantiomeric excess.

44 . A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

45 . (canceled)

46 . A method of treating a medical disorder in a patient, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 to treat the disorder.

47 . (canceled)

48 . A method of treating a medical disorder in a patient, comprising orally administering to a patient in need thereof a therapeutically effective amount of a compound of Formula I-J to treat the disorder, wherein Formula I-J is represented by:

or a pharmaceutically acceptable salt thereof, wherein:

Z is H or D, provided that the abundance of deuterium in Z is at least 30%;

R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , and R is are independently H or D; and

the compound has a stereochemical purity of at least 75% enantiomeric excess at the carbon atom bearing variable Z.

49 . (canceled)

50 . The method of claim 48 , wherein the compound is

having a stereochemical purity of at least 85% enantiomeric excess, or a pharmaceutically acceptable salt thereof.

51 . (canceled)

52 . The method of claim 46 , wherein the disorder is a metabolic disorder.

53 . The method of claim 52 , wherein the metabolic disorder is nonalcoholic steatohepatitis.

54 . The method of claim 52 , wherein the metabolic disorder is type I diabetes, non-alcoholic fatty liver disease, viral hepatitis, liver cirrhosis, liver fibrosis, diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, beta cell depletion, insulin resistance in a patient with congenital adrenal hyperplasia treated with a glucocorticoid, dysmetabolism in peritoneal dialysis patients, reduced insulin secretion, improper distribution of brown fat cells and white fat cells, obesity, or improper modulation of leptin levels.

56 - 72 . (canceled)