IP Library › Granted Patent US 10,828,302
Granted Patent B2
US 10,828,302 · App. 15/454,628 · Granted Nov 10, 2020

Methods of treating depression using orexin-2 receptor antagonists

Inventors: Peter De Boer (Breda, NL); Justine M. Kent (Titusville, NJ); Wayne C. Drevets (Titusville, NJ)
Assignee: Janssen Pharmaceutica NV
A61K31/506A61K9/0095A61K9/10A61K9/2018A61K9/2027A61K45/06A61K47/38A61K31/50A61K31/53
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Quick Facts
Patent No.
US 10,828,302
App. No.
15/454,628
Granted
Nov 10, 2020
Kind
B2
Abstract

The present disclosure is directed to, inter alia, methods of treating a subject suffering from or diagnosed with depression, comprising administering to a subject in need of such treatment an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R 1 to R 4 are described herein and wherein the compound is administered prior to sleep.

Claims (65)

1. A method of treating depression in a subject, comprising administering to the subject in need of such treatment an effective amount of a compound of formula (I):

wherein:

R 1 is C 1-4 alkyl;

R 2 is C 1-4 alkyl;

R 3 is H or halogen; and

R 4 is H or C 1-4 alkoxy;

or a pharmaceutically acceptable salt or hydrate thereof

2. The method of claim 1 wherein the subject is not suffering from or diagnosed with an insomnia disorder.

3. The method of claim 1 , wherein R 3 is halogen.

4. The method of claim 3 , wherein R 3 is fluorine.

5. The method of claim 1 , wherein R 4 is H.

6. The method of claim 1 , wherein R 4 is C 1-4 alkoxy.

7. The method of claim 6 , wherein R 4 is methoxy.

8. The method of claim 1 , wherein R 3 is H.

9. The method of claim 1 , wherein R 1 is CH 3.

10. The method of claim 1 , wherein R 2 is CH 3.

11. The method of claim 1 , wherein the compound is [5-(4,6-dimethyl-pyrimidin-2-yl)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl]-(2-fluoro-6-[1,2,3]triazol-2-yl-phenyl)-methanone or a pharmaceutically acceptable salt thereof.

12. The method of claim 1 , wherein the compound is [5-(4,6-dimethyl-pyrimidin-2-yl)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl]-(2-fluoro-6-[1,2,3]triazol-2-yl-phenyl)-methanone.

13. The method of claim 1 , wherein the compound is [5-(4,6-dimethyl-pyrimidin-2-yl)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl]-(2-fluoro- 6 -[1,2,3]triazol-2-yl-phenyl)-methanone hydrochloride.

14. The method of claim 1 wherein the compound is (5-(4,6-dimethylpyrimidin-2-yl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)(4-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone or a pharmaceutically acceptable salt thereof

15. The method of claim 1 , wherein the compound is (5-(4,6-dimethylpyrimidin-2-yl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)(4-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone.

16. The method of claim 1 , wherein the compound is administered at night.

17. The method of claim 1 , wherein the compound is administered daily.

18. The method of claim 1 , wherein the compound is administered orally.

19. The method of claim 1 , wherein the effective amount is about 10 to about 40 mg.

20. The method of claim 1 , wherein the depression is major depressive disorder.

21. The method of claim 1 , wherein the depression is treatment resistant depression.

22. The method of claim 1 , further comprising administering a second antidepressant.

23. The method of claim 22 , wherein said second antidepressant is a selective serotonin reuptake inhibitor, serotonin and noradrenaline reuptake inhibitor, or combinations thereof.

24. The method of claim 2 , wherein the compound is [5-(4,6-dimethyl-pyrimidin-2-yl)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl]-(2-fluoro- 6 ]1,2,3]triazol-2-yl-phenyl)-methanone or a pharmaceutically acceptable salt thereof.

25. The method of claim 24 , wherein the compound is administered at night.

26. The method of claim 25 , wherein the depression is major depressive disorder.

27. The method of claim 26 , further comprising administering a second antidepressant.

28. The method of claim 16 , wherein the compound is [5-(4,6-dimethyl-pyrimidin-2-yl)-hexahydro-pyrrolo [3,4-pyrrolo-2-yl]-(2-fluoro-6-[1,2,3]triazol-2-yl-phenyl)-methanone or a pharmaceutically acceptable salt thereof.

29. The method of claim 28 , wherein the depression is major depressive disorder.

30. The method of claim 29 , further comprising administering a second antidepressant.

31. The method of claim 20 , wherein the compound is [5(4,6-dimethyl-pyrimidin-2-yl)-hexahydro-pyrrolo [3,4-c]pyrrol-2-yl]-(2-fluoro-6-[1,2,3]triazol-2-yl-phenyl)-methanone or a pharmaceutically acceptable salt thereof.

32. The method of claim 31 , further comprising administering a second antidepressant.

33. The method of claim 22 , wherein the compound is [5(4,6-dimethyl-pyrimidin-2-yl)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl]-(2-fluoro-6-[1,2,3]triazol-2-yl-phenyl)-methanone or a pharmaceutically acceptable salt thereof.

34. The method of claim 32 , wherein the second antidepressant is a selective serotonin reuptake inhibitor, serotonin and noradrenaline reuptake inhibitor, or combinations thereof.

35. The method of claim 32 , wherein the effective amount of the compound is about 10 to about 40 mg.

36. The method of claim 34 , wherein the effective amount of the compound is about 10 to about 40 mg.

37. The method of claim 32 , wherein the effective amount of the compound is about 20 mg.

38. The method of claim 34 , wherein the effective amount of the compound is about 20 mg.

39. The method of claim 35 , wherein the compound is administered once daily.

40. The method of claim 36 , wherein the compound is administered once daily.

41. The method of claim 37 , wherein the compound is administered once daily.

42. The method of claim 38 , wherein the compound is administered once daily.

43. The method of claim 1 , wherein the compound is administered prior to sleep.

44. The method of claim 43 , wherein the compound is administered at night.

45. The method of claim 44 , wherein the compound is [5(4,6-dimethyl-pyrimidin-2-yl)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl]-(2-fluoro-6-[1,2,3]triazol-2-yl-phenyl)-methanone or a pharmaceutically acceptable salt thereof.

46. The method of claim 45 , wherein the depression is major depressive disorder.

47. The method of claim 46 , further comprising administering a second antidepressant.

48. The method of claim 46 , wherein the compound is [5(4,6-dimethyl-pyrimidin-2-yl)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl]-(2-fluoro- 6 -[1,2,3]triazol-2-yl-phenyl)-methanone or a pharmaceutically acceptable salt thereof.

49. The method of claim 48 , wherein the depression is major depressive disorder.

50. The method of claim 49 , further comprising administering a second antidepressant.

51. The method of claim 50 , wherein the second antidepressant is a selective serotonin reuptake inhibitor, serotonin and noradrenaline reuptake inhibitor, or combinations thereof.

52. The method of claim 50 , wherein the effective amount of the compound is about 10 to about 40 mg.

53. The method of claim 51 , wherein the effective amount of the compound is about 10 to about 40 mg.

54. The method of claim 50 , wherein the effective amount of the compound is about 20 mg.

55. The method of claim 51 , wherein the effective amount of the compound is about 20 mg.

56. The method of claim 52 , wherein the compound is administered once daily.

57. The method of claim 53 , wherein the compound is administered once daily.

58. The method of claim 54 , wherein the compound is administered once daily.

59. The method of claim 55 , wherein the compound is administered once daily.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 12, 2020
From: DE BOER, PETER; KENT, JUSTINE M.; DREVETS, WAYNE C.
To: JANSSEN PHARMACEUTICA NV
Reel/Frame 052099/0820 →
Continuity (2)
Provisional Application 62306487 · Mar 10, 2016
Related Publication 20170258790A1 · Sep 14, 2017
Cited By (2)
US 12,201,634 US 12,378,254