Methods of treating neurological, metabolic, and other disorders using enantiopure deuterium-enriched pioglitazone
AssigneePoxel
InventorsSheila DeWitt, Vincent Jacques, Leonardus van der Ploeg
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Abstract
The invention provides enantiopure deuterium-enriched pioglitazone, pharmaceutical compositions, and methods of treating neurological disorders, cancer, respiratory disorders, metabolic disorders, and other disorders using enantiopure deuterium-enriched pioglitazone. A preferred aspect of the invention provides methods of treating Alzheimer's disease, non-small cell lung cancer, hepatocellular carcinoma, and chronic obstructive pulmonary disease using enantiopure deuterium-enriched pioglitazone.
Claims18
A method of treating a metabolic disorder selected from the group consisting of 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, and improper modulation of leptin levels, comprising administering to a patient in need thereof a therapeutically effective amount of a deuterium-enriched compound of Formula II having an optical purity of at least 75% enantiomeric excess to treat the disorder, wherein Formula II is represented by:
- or a pharmaceutically acceptable salt thereof, wherein:
- A1, A2, A3, and A4 are independently —C(R9)(R10)—;
- A5 is —C(R11)(R12)(R13);
- R1, R2, R3, R4, R5, R6, R7, and R8 are independently H or D;
- R9, R10, R11, R12, and R13 each represent independently for each occurrence H or D;
- and
- Z is D.
A method of treating a metabolic disorder selected from the group consisting of 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, and improper modulation of leptin levels, comprising administering to a patient in need thereof a therapeutically effective amount of a deuterium-enriched compound of Formula I having an optical purity of at least 75% enantiomeric excess to treat the neurological disorder, wherein Formula I is represented by:
- or a pharmaceutically acceptable salt thereof, wherein:
- A1, A2, A3, and A4 are independently —C(R9)(R10)—;
- A5 is —C(R11)(R12)(R13);
- R1, R2, R3, R4, R5, R6, R7, and R8 are independently H or D;
- R9, R10, R11, R12, and R13 each represent independently for each occurrence H or D;
- and
- Z is D.
Dependencies are inferred from the claim text.