Pyridine derivative

• US 8,946,264 B2
• Filed: 10/20/2012
• Issued: 02/03/2015
• Est. Priority Date: 03/05/2009
• Status: Expired due to Fees

• Current Assignee: Daiichi Sankyo Company Limited
• Original Assignee: Daiichi Sankyo Company Limited
• Inventors: Shinozuka, Tsuyoshi, Fujii, Kunihiko, Mori, Makoto, Tsukada, Tomoharu
• Primary Examiner(s): Morris, Patricia L
• Application Number:
  US13/656,664
• Publication Number:
  US 20130045994A1
• Time in Patent Office: 836 Days
• Field of Search: 546/273.4, 514/338
• US Class Current: 514/338
• 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 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: A61P 19/06 Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/04 Artificial tears; Irrigation solutions
• 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 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 : Antihyperlipidemics
• CPC Class Codes: A61P 3/08 : for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• 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 5/50 : for increasing or potentiating the activity of insulin
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links

Abstract

The present invention relates to a novel pyridine derivative or a pharmacologically acceptable ester thereof, or a pharmacologically acceptable salt of the derivative or ester, which has an excellent hypoglycemic effect or treats and/or prevents the onset of a disorder of carbohydrate or lipid metabolism or a disease mediated by peroxisome proliferator-activated receptor (PPAR) γ. A compound represented by the general formula (I):

[wherein R represents a pyridyl group substituted with 1 to 3 group(s) independently selected from Substituent Group A, and Substituent Group A represents a halogen atom, a C₁-C₆ alkyl group and a C₁-C₆ alkoxy group] or a pharmacologically acceptable ester thereof, or a pharmacologically acceptable salt of the compound or ester.

Claims

1. A compound having a formula (I):

2. The compound according to claim 1 that is:

3-({6-[(3,5-dimethylpyridin-2-yl)oxy]-1-methyl-1H-benzimidazol-2-yl}methoxy)benzoic acid.

3. The compound according to claim 1 that is:

a pharmacologically acceptable salt of 3-({6-[(3,5-dimethylpyridin-2-yl)oxy]-1-methyl-1H-benzimidazol-2-yl}methoxy)benzoic acid.

4. The compound according to claim 1 that is:

a calcium salt of 3-({6-[(3,5-dimethylpyridin-2-yl)oxy]-1-methyl-1H-benzimidazol-2-yl}methoxy)benzoic acid.

5. The compound according to claim 1 that is:

a sodium salt of 3-({6-[(3,5-dimethylpyridin-2-yl)oxy]-1-methyl-1H-benzimidazol-2-yl}methoxy)benzoic acid.

6. The compound according to claim 1 that is:

a hydrochloride salt of 3-({6-[(3,5-dimethylpyridin-2-yl)oxy]-1-methyl-1H-benzimidazol-2-yl}methoxy)benzoic acid.

7. A composition comprising the compound, or the pharmacologically acceptable C₁ to C₄ alkyl ester of the compound, or the pharmacologically acceptable salt of the compound or the ester of claim 1 and an inert carrier or diluent.

8. The composition according to claim 7, further comprising an additive.

9. The composition according to claim 8, wherein the additive is selected from the group consisting of:

excipients, lubricants, binders, disintegrants, stabilizers, corrigents, diluents, and a combination thereof.

10. The composition according to claim 7, wherein the composition is for oral administration.

11. A method for the treatment of a disease selected from the group consisting of:

diabetes, type II diabetes, impaired glucose tolerance, and gestational diabetes mellitus, the method comprising

administering a pharmacologically effective amount of the compound, or the pharmacologically acceptable ester of the compound, or the pharmacologically acceptable salt of the compound or the ester of claim 1 to a warm-blooded animal.

12. The method according to claim 11, wherein the warm-blooded animal is a human.

13. The method according to claim 12, wherein the disease is diabetes.

14. The method according to claim 12, wherein the disease is type II diabetes.

15. A method for lowering blood glucose levels in a human comprising

administering a pharmacologically effective amount of the compound, or the pharmacologically acceptable ester of the compound, or the pharmacologically acceptable salt of the compound or the ester of claim 1 to the human.

16. A method for improving insulin resistance in a human comprising

administering a pharmacologically effective amount of the compound, or the pharmacologically acceptable ester of the compound, or the pharmacologically acceptable salt of the compound or the ester of claim 1 to the human.

17. A method for activating peroxisome proliferator-activated receptor (PPAR) γ

in a human, comprising

administering a pharmacologically effective amount of the compound, or the pharmacologically acceptable ester of the compound, or the pharmacologically acceptable salt of the compound or the ester of claim 1 to the human.