5-DEUTERO-THIAZOLIDINE-2,4-DIONE COMPOUNDS AND METHODS OF TREATING MEDICAL DISORDERS USING SAME
The invention provides deuterium-enriched thiazolidine-2,4-dione compounds (i.e., deuterium-enriched glitazone compounds), enantiopure forms of deuterium-enriched glitazone compounds, pharmaceutical compositions, and methods of treating medical disorders, such as a metabolic disorder, neurological disorder, cancer, or other disorder using deuterium-enriched glitazone compounds, which are preferably in enantiopure form.
1 - 72 . (canceled)
73 . A compound of Formula I-E or II-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 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 independently H or D; and
the compound has an enantiomeric excess of at least 75%.
74 . The compound of claim 73 , 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.
75 . The compound of claim 73 , wherein the compound is
having a stereochemical purity of at least 85% enantiomeric excess, or a pharmaceutically acceptable salt thereof.
76 . The compound of claim 75 , wherein the abundance of deuterium in Z is at least 60%.
77 . The compound of claim 75 , wherein the abundance of deuterium in Z is at least 90%.
78 . The compound of claim 75 , wherein the compound has a stereochemical purity of at least 90% enantiomeric excess.
79 . The compound of claim 73 , wherein the compound is
having a stereochemical purity of at least 85% enantiomeric excess, or a pharmaceutically acceptable salt thereof.
80 . The compound of claim 79 , wherein the abundance of deuterium in Z is at least 60%.
81 . The compound of claim 79 , wherein the abundance of deuterium in Z is at least 90%.
82 . The compound of claim 79 , wherein the compound has a stereochemical purity of at least 90% enantiomeric excess.
83 . A pharmaceutical composition comprising a compound of claim 73 and a pharmaceutically acceptable carrier.
84 . A compound of Formula I-J or Formula II-J:
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 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.
85 . The compound of claim 84 , 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 , and R 18 are H.
86 . The compound of claim 84 , wherein the compound is
having a stereochemical purity of at least 85% enantiomeric excess, or a pharmaceutically acceptable salt thereof.
87 . The compound of claim 86 , wherein the abundance of deuterium in Z is at least 60%.
88 . The compound of claim 86 , wherein the abundance of deuterium in Z is at least 90%.
89 . The compound of claim 86 , wherein the compound has a stereochemical purity of at least 90% enantiomeric excess.
90 . The compound of claim 84 , wherein the compound is
having a stereochemical purity of at least 85% enantiomeric excess, or a pharmaceutically acceptable salt thereof.
91 . The compound of claim 90 , wherein the abundance of deuterium in Z is at least 60%.
92 . The compound of claim 90 , wherein the abundance of deuterium in Z is at least 90%.
93 . The compound of claim 90 , wherein the compound has a stereochemical purity of at least 90% enantiomeric excess.
94 . A pharmaceutical composition comprising a compound of claim 84 and a pharmaceutically acceptable carrier.
95 . 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 73 to treat the disorder.