Thiazolidinedione analogues

• US 20120015982A1
• Filed: 05/18/2011
• Published: 01/19/2012
• Est. Priority Date: 03/16/2006
• Status: Active Grant

• Current Assignee: Metabolic Solution Development Company
• Original Assignee: Metabolic Solution Development Company
• Inventors: Colca, Gerard R., Kletzien, Rolf F.
• Granted Patent: US 8,389,556 B2
• Time in Patent Office: Days
• US Class Current: 514/342
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

The present invention relates to thiazolidinedione analogues that are useful for treating metabolic inflammation mediated diseases such as diabetes.

Claims

1. A method of treating a metabolic inflammation mediated disease comprising administering to a patient a pharmaceutical composition including a compound of formula I:

6. The method of claim 1, wherein R₁ is an optionally substituted straight or branched C_1-6 alkyl, an optionally substituted straight or branched C_2-6 alkenyl, or an optionally substituted straight or branched C_2-6 alkynyl.

7. The method of claim 1, wherein R₁ is a methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, pentyl, or hexyl, each of which is unsubstituted.

8. The method of claim 1, wherein R₁ is a hydrogen or a halo.

9. The method of claim 1, wherein R₂ is hydroxy or oxo.

10. The method of claim 1, wherein R₂ is an optionally substituted C_1-6 aliphatic.

11. The method of claim 1, wherein R₂ is an optionally substituted straight or branched C_1-6 alkyl, an optionally substituted straight or branched C_2-6 alkenyl, or an optionally substituted straight or branched C_1-6 alkynyl.

12. The method of claim 1, wherein R₂ is a methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, pentyl, or hexyl, each of which is optionally substituted with hydroxy.

13. The method of claim 1, wherein R₂ is methyl or ethyl, each of which is substituted with hydroxy.

14. The method of claim 1, wherein R₃ is hydrogen or halo.

15. The method of claim 1, wherein R₃ is an optionally substituted C_1-6 aliphatic.

16. The method of claim 1, wherein R₃ is an optionally substituted straight or branched C_1-6 alkyl, an optionally substituted straight or branched C_2-6 alkenyl, or an optionally substituted straight or branched C_2-6 alkynyl.

17. The method of claim 1, wherein R₃ is a methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, pentyl, or hexyl, each of which is unsubstituted.

18. The method of claim 1, wherein ring A is a monocyclic 5-6 membered heteroaryl having 1-3 heteroatoms selected from N, O, or S.

19. The method of claim 1, wherein ring A is a furan-yl, thiophene-yl, pyrrole-yl, pyridine-yl, pyrazole-yl, 1,3,4-thiadiaziole-yl, 1,3,5-triazine-yl, pyrazine-yl, pyrimidine-yl, pyridazine-yl, isoxazole-yl, or isothiazole-yl.

20. The method of claim 1, wherein ring A is a pyridine-yl.

21. The method of claim 1, wherein ring A is a pyridine-2-yl, pyridine-3-yl, or pyridine-4-yl.

22. The method of claim 1, wherein ring A is a pyridine-2-yl or pyridine-3-yl.

2. A method of treating a metabolic inflammation mediated disease comprising administering to a patient a pharmaceutical composition including a compound of formula III:

3. A method of treating a metabolic inflammation mediated disease comprising administering to a patient a pharmaceutical composition including a compound of formula IV:

4. A method of treating a metabolic inflammation mediated disease comprising administering to a patient a pharmaceutical composition including a compound of formula V:

5. A method of treating a metabolic inflammation mediated disease comprising administering to a patient a pharmaceutical composition including a compound of formula VI:

23. A method of treating a metabolic inflammation mediated disease comprising administering to a patient a pharmaceutical composition including a compound selected from

24. A method of treating or reducing the severity of inflammatory disease comprising administering metformin and a compound of formula I

25. A method of treating or reducing the severity of a disease in a patient, wherein said disease is selected from dyslipidemia, central obesity, rheumatoid arthritis, lupus, myasthenia gravis, vasculitis, multiple schlerosis, Chronic Obstructive Pulmonary Disease (COPD), inflammatory bowel disease, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), acute allergic reactions, transplant rejection, Alzheimer'"'"'s disease, Parkinson'"'"'s disease, and multiple sclerosis, wherein said method comprises the step of contacting said patient with a compound of formula I:

26. A pharmaceutical composition useful for treating metabolic mediated disease comprising metformin and a compound of formula I: