5-DEUTERO-THIAZOLIDINYLDIONE COMPOUNDS AND METHODS OF TREATING MEDICAL DISORDERS USING SAME

1 . A deuterium-enriched compound represented by Formula I:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 , R 2 , R 3 , R 4 , and R 5 are independently hydrogen, halogen, hydroxyl, alkyl, cycloalkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxyl, cyano, nitro, —C(O)-alkyl, —CO 2 -alkyl, or —CO 2 H; or R 1 and R 2 are taken together to form the 4-carbon chain —CH═CH—CH═CH— which results in a fused phenyl group at the R 1 and R 2 positions, wherein said fused phenyl group is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, hydroxyl, alkyl, cycloalkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxyl, cyano, nitro, and —S(O 2 )alkyl;

Y is N or —C(R 5 )—;

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

any hydrogen atom in Formula I may be replaced with D.

2 . A deuterium-enriched compound represented by Formula II:

or a pharmaceutically acceptable salt thereof, wherein:

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

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

3 . (canceled)

4 . The compound of claim 2 , wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and R 12 are H.

5 . The compound of claim 2 , wherein the compound is represented by Formula II-A:

or a pharmaceutically acceptable salt thereof, wherein:

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

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

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

6 . (canceled)

7 . The compound of claim 5 , wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and R 12 are H.

8 . The compound of claim 2 , wherein the compound is represented by Formula II-B:

or a pharmaceutically acceptable salt thereof, wherein:

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

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

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

9 . (canceled)

10 . The compound of claim 8 , wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and R 12 are H.

11 . (canceled)

12 . (canceled)

13 . The compound of claim 2 , wherein the abundance of deuterium in Z is at least 90%.

14 . The compound of claim 2 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

15 . The compound of claim 2 , wherein the compound is

16 . The compound of claim 2 , wherein the compound is

or a pharmaceutically acceptable salt thereof, wherein the compound has a stereochemical purity of at least 75% enantiomeric excess at the carbon atom bearing D.

17 . The compound of claim 2 , wherein the compound is

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

18 . The compound of claim 2 , wherein the compound is

or a pharmaceutically acceptable salt thereof, wherein the compound has a stereochemical purity of at least 75% enantiomeric excess at the carbon atom bearing D.

19 . The compound of claim 2 , wherein the compound is

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

20 . A deuterium-enriched compound represented by Formula III:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is alkyl, cycloalkyl, or haloalkyl;

R 2 , R 3 , and R 4 each represent independently for each occurrence hydrogen, halogen, hydroxyl, alkyl, cycloalkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxyl, cyano, nitro, —C(O)-alkyl, —CO 2 -alkyl, or —CO 2 H;

m and n are independently 1, 2, or 3;

Y is N or —C(R 4 )—;

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

any hydrogen atom in Formula III may be replaced with D.

21 - 38 . (canceled)

39 . A deuterium-enriched compound represented by Formula V:

or a pharmaceutically acceptable salt thereof, wherein:

Ar 1 is arylene or heteroarylene, each of which is optionally substituted with from 1 to 4 R a groups;

Ar 2 is aryl or heteroaryl, each of which is optionally substituted with from 1-5 R a groups;

X and Y are independently —O—, —S—, —N(R b )—, or —CH 2 —;

Y* is O or S;

n is 0, 1, 2, or 3;

R a is C 1-15 alkanoyl, C 1-15 alkyl, C 2-15 alkenyl, C 2-15 alkynyl, halogen, —OR b , aryl, heteroaryl, cycloalkyl having from 3-8 carbon atoms, or a 3-10 membered heterocyclyl having one or more heteroatoms selected from N, S, O, and SO 2 ; wherein said alkyl, alkenyl, alkynyl, and alkanoyl are optionally substituted with from 1-5 groups selected from R c , and said aryl, heteroaryl, cycloalkyl, and heterocyclyl are optionally substituted with 1 to 5 groups selected from R d ;

R b is hydrogen, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, C 1-15 alkanoyl, or C 3-8 cycloalkyl, wherein said alkyl, alkenyl, and alkynyl are optionally substituted with one to four substituents independently selected from R c , and said cycloalkyl, aryl, and heteroaryl are optionally substituted with one to four substituents independently selected from R d ;

R c represents independently for each occurrence halogen, aryl, heteroaryl, cyano, nitro, —OR f , —S(O) m R f (where m=0, 1, or 2, provided that R f is not H when m is 1 or 2), —NR f R f , —NR f COR f , —NR f CO 2 R f , —NR f CON(R f ) 2 , —NR f SO 2 R f (provided that R f is not H), —COR f , —CO 2 R f , —CON(R f ) 2 , —SO 2 N(R f ) 2 , —OCON(R f ) 2 , or C 3-8 cycloalkyl; wherein said cycloalkyl, aryl, and heteroaryl are optionally substituted with 1 to 3 substituents independent selected from the group consisting of halogen and C 1-6 alkyl;

R d represents independently for each occurrence a group selected from R c , C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, aralkyl, or heteroaralkyl, wherein said alkyl, alkenyl, alkynyl, aralkyl, and heteroaralkyl are optionally substituted with a group independently selected from R e ;

R e represents independently for each occurrence halogen, amino, carboxy, C 1-4 alkyl, C 1-4 alkoxy, hydroxy, aryl, aralkyl, or aryloxy;

R f represents independently for each occurrence hydrogen, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, C 1-15 alkanoyl, or C 3-8 cycloalkyl, wherein said alkyl, alkenyl, alkynyl, aryl, heteroaryl, alkanoyl, and cycloalkyl are optionally substituted with one to four groups independently selected from R e ; and

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

40 - 58 . (canceled)

59 . The compound of claim 16 , wherein the compound has an enantiomeric excess of at least 90%.

60 . The compound of claim 16 , wherein the compound has an enantiomeric excess of at least 95%.

61 . (canceled)

62 . (canceled)

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

64 . (canceled)

65 . 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.

66 . The method of claim 65 , wherein the disorder is a metabolic disorder.

67 - 86 . (canceled)