Dipeptidyl peptidase-IV inhibitors

• US 8,076,330 B2
• Filed: 01/13/2011
• Issued: 12/13/2011
• Est. Priority Date: 04/22/2005
• Status: Expired due to Fees

• Current Assignee: Amgen Inc.
• Original Assignee: Amgen Inc.
• Inventors: Kroth, Heiko, Feuerstein, Tim, Richter, Frank, Boer, Jürgen, Essers, Michael, Nolte, Bert, Schneider, Matthias, Hochgürtel, Matthias, Frickel, Fritz-Frieder, Taveras, Arthur G., Steeneck, Christoph
• Primary Examiner(s): Anderson, Rebecca
• Assistant Examiner(s): SHTERENGARTS, SAMANTHA L
• Application Number:
  US13/006,363
• Publication Number:
  US 20110112051A1
• Time in Patent Office: 334 Days
• Field of Search: 514/236.2, 514/235.5, 514/381, 514/408, 544/111, 544/132, 544/152, 548/250, 548/530
• US Class Current: 514/236.2
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• 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 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 15/16 Masculine contraceptives
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/26 Psychostimulants, e.g. nicotine, cocaine
• 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 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 25/32 Alcohol-abuse
• CPC Class Codes: A61P 25/34 Tobacco-abuse
• CPC Class Codes: A61P 25/36 Opioid-abuse
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 27/06 : Antiglaucoma agents or miotics
• CPC Class Codes: A61P 27/12 : for cataracts
• 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 31/18 : for HIV
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 37/02 : Immunomodulators
• 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 5/38 : of the suprarenal hormones
• 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 207/16 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 209/02 : condensed with one carbocyclic ring
• CPC Class Codes: C07D 209/52 : condensed with a ring other than six-membered
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 487/08 : Bridged systems
• CPC Class Codes: C07D 495/04 : Ortho-condensed systems

Abstract

The present invention relates generally to pyrrolidine and thiazolidine DPP-IV inhibitor compounds. The present invention also provides synthetic methods for preparation of such compounds, methods of inhibiting DPP-IV using such compounds and pharmaceutical formulations containing them for treatment of DPP-IV mediated diseases, in particular, Type-2 diabetes.

Claims

1. A compound of formula (I):

A-B-D 

 

(I)

or a pharmaceutically acceptable salt thereof,

wherein A is;

2. A compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein:

Q^b is CH;

U is (—

CH₂—

)_p;

p is 1;

R⁷ and R⁸ are each independently H or alkyl; and

R⁹ is H.

3. A compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein:

D is;

4. A compound of claim 1, or a pharmaceutically acceptable salt, thereof, wherein:

Y is —

CH₂—

CH₂—

.

5. A compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein:

Y is —

CH₂—

CH₂—

;

D is

6. A compound of claim 1, or a pharmaceutically acceptable salt, thereof, wherein:

A is;

7. A compound of claim 1, or a pharmaceutically acceptable salt, thereof, wherein:

A is;

21. A pharmaceutical composition comprising a compound in accordance with claim 1, or a pharmaceutically acceptable salt thereof.

22. A method of treating type-2 diabetes comprising administering to a patient in need thereof an effective amount of a compound in accordance with claim 1, or a pharmaceutically acceptable salt thereof.

23. A pharmaceutical composition comprising a compound in accordance with claim 7, or a pharmaceutically acceptable salt thereof.

24. A method of treating type-2 diabetes comprising administering to a patient in need thereof an effective amount of a compound in accordance with claim 7, or a pharmaceutically acceptable salt thereof.

8. A compound according to the following formula:

9. A compound according to the following formula:

10. A compound according to the following formula:

11. A compound according to the following formula:

12. A compound according to the following formula:

13. A compound according to the following formula:

14. A compound according to the following formula:

15. A compound according to the following formula:

16. A compound according to the following formula:

17. A compound according to the following formula:

18. A compound according to the following formula:

19. A compound according to the following formula:

20. A compound according to the following formula: