Dipeptidyl peptidase inhibitors

• US 7,807,689 B2
• Filed: 03/15/2005
• Issued: 10/05/2010
• Est. Priority Date: 03/15/2004
• Status: Active Grant

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Takeda Pharmaceutical Company Limited
• Inventors: Isbester, Paul K., Ulysse, Luckner G., Zhang, Zhiyuan, Palmer, Grant J., Elder, Bruce J.
• Primary Examiner(s): Balasubramanian; Venkataraman
• Application Number:
  US11/080,992
• Publication Number:
  US 20050261271A1
• Time in Patent Office: 2,030 Days
• Field of Search: 544/309, 514/274
• US Class Current: 514/274
• 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 15/18 Feminine contraceptives
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/10 for osteoporosis
• 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 3/10 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 35/04 specific for metastasis
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 39/02 Antidotes
• CPC Class Codes: A61P 5/02 of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: C07D 239/545 : with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
• CPC Class Codes: C07D 401/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/14 : containing three or more hetero rings
• CPC Class Codes: C07D 403/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 403/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/14 : containing three or more hetero rings

Abstract

The present invention provides a compound of the formula:

• • or stereoisomers or pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, articles of manufacture comprising the same, and methods of using the same.

Claims

1. A compound of the formula

2. The compound according to claim 1, wherein the compound is present as a mixture of stereoisomers.

3. The compound according to claim 1, wherein the compound comprises a single stereoisomer.

45. A method of treating breast cancer in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a compound according to claim 1.

4. A compound of the formula

5. A compound of the formula

6. The compound according to claim 5, wherein the compound is present as a mixture of stereoisomers.

7. The compound according to claim 5, wherein the compound is present as a single stereoisomer.

8. A compound of the formula

46. A method of treating type II diabetes in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a compound according to claim 8.

47. A method of treating type I diabetes in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a compound according to claim 8.

48. A method of treating breast cancer in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a compound according to claim 8.

9. A compound of the formula

10. The compound according to claim 9, wherein the compound is present as a mixture of stereoisomers.

11. The compound according to claim 10, wherein the compound is present as a single stereoisomer.

12. A compound of the formula

49. A method of treating type II diabetes in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a compound according to claim 12.

50. A method of treating type I diabetes in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a compound according to claim 12.

51. A method of treating breast cancer in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a compound according to claim 12.

13. A pharmaceutical composition comprising, as an active ingredient, a compound of the formula

14. The pharmaceutical composition according to claim 13, wherein the composition is a solid formulation adapted for oral administration.

15. The pharmaceutical composition according to claim 13, wherein the composition is a tablet.

16. The pharmaceutical composition according to claim 13, wherein the composition is a liquid formulation adapted for oral administration.

17. The pharmaceutical composition according to claim 13, wherein the composition is a liquid formulation adapted for parenteral administration.

18. The pharmaceutical composition according to claim 13, wherein the composition is adapted for administration by a route selected from the group consisting of orally, parenterally, intraperitoneally, intravenously, intraarterially, transdermally, sublingually, intramuscularly, rectally, transbuccally, intranasally, liposomally, via inhalation, vaginally, intraoccularly, via local delivery, subcutaneously, intraadiposally, intraarticularly, and intrathecally.

19. A pharmaceutical composition comprising, as an active ingredient, a compound of the formula

20. The pharmaceutical composition according to claim 19, wherein the composition is a solid formulation adapted for oral administration.

21. The pharmaceutical composition according to claim 19, wherein the composition is a tablet.

22. The pharmaceutical composition according to claim 19, wherein the composition is a liquid formulation adapted for oral administration.

23. The pharmaceutical composition according to claim 19, wherein the composition is a liquid formulation adapted for parenteral administration.

24. The pharmaceutical composition according to claim 19, wherein the composition is adapted for administration by a route selected from the group consisting of orally, parenterally, intraperitoneally, intravenously, intraarterially, transdermally, sublingually, intramuscularly, rectally, transbuccally, intranasally, liposomally, via inhalation, vaginally, intraoccularly, via local delivery, subcutaneously, intraadiposally, intraarticularly, and intrathecally.

25. A pharmaceutical composition comprising, as an active ingredient, a compound of the formula

26. The pharmaceutical composition according to claim 25, wherein the composition is a solid formulation adapted for oral administration.

27. The pharmaceutical composition according to claim 25, wherein the composition is a tablet.

28. The pharmaceutical composition according to claim 25, wherein the composition is a liquid formulation adapted for oral administration.

29. The pharmaceutical composition according to claim 25, wherein the composition is a liquid formulation adapted for parenteral administration.

30. The pharmaceutical composition according to claim 25, wherein the composition is adapted for administration by a route selected from the group consisting of orally, parenterally, intraperitoneally, intravenously, intraarterially, transdermally, sublingually, intramuscularly, rectally, transbuccally, intranasally, liposomally, via inhalation, vaginally, intraoccularly, via local delivery, subcutaneously, intraadiposally, intraarticularly, and intrathecally.

31. An article of manufacture comprising:

a compound of the formula

32. The article of manufacture of claim 31, wherein the packaging material comprises a container for housing the compound.

33. The article of manufacture of claim 32, wherein the container comprises a label indicating one or more members of the group consisting of a disease state for which the compound is to be administered wherein the disease state is diabetes, storage information, dosing information and/or instructions regarding how to administer the composition.

34. The article of manufacture of claim 31, wherein the article of manufacture comprises the compound in a multiple dose form.

35. An article of manufacture comprising:

a compound of the formula

36. The article of manufacture of claim 35, wherein the packaging material comprises a container for housing the compound.

37. The article of manufacture of claim 36, wherein the container comprises a label indicating one or more members of the group consisting of a disease state for which the compound is to be administered wherein the disease state is diabetes, storage information, dosing information and/or instructions regarding how to administer the composition.

38. The article of manufacture of claim 35, wherein the article of manufacture comprises the compound in a multiple dose form.

39. An article of manufacture comprising:

a compound of the formula

40. The article of manufacture of claim 39, wherein the packaging material comprises a container for housing the compound.

41. The article of manufacture of claim 40, wherein the container comprises a label indicating one or more members of the group consisting of a disease state for which the compound is to be administered wherein the disease state is diabetes, storage information, dosing information and/or instructions regarding how to administer the composition.

42. The article of manufacture of claim 39, wherein the article of manufacture comprises the compound in a multiple dose form.

43. A method of treating type II diabetes in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a compound of the formula

44. A method of treating type I diabetes in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a compound of the formula