Quinoline and isoquinoline derivatives as phosphodiesterase 10 inhibitors

• US 20070299067A1
• Filed: 03/08/2007
• Published: 12/27/2007
• Est. Priority Date: 03/08/2006
• Status: Abandoned Application

• Current Assignee: Amgen Inc., Memory Pharmaceuticals Corp. (Roche Holding AG)
• Original Assignee: Amgen Inc.
• Inventors: Liu, Ruiping, Hitchcock, Stephen, Conticello, Richard, Hopper, Allen, Arrington, Mark
• Application Number:
  US11/716,307
• Publication Number:
  US 20070299067A1
• Time in Patent Office: Days
• US Class Current: 514/233.5
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 413/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 417/04 directly linked by a ring-member-to-ring-member bond

Abstract

The present invention is directed to certain quinoline and isoquinoline compounds that are PDE10 inhibitors, pharmaceutical compositions containing such compounds and processes for preparing such compounds. The invention is also directed to methods of treating diseases mediated by PDE10 enzyme, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

Claims

1. A compound of Formula (I):

2. The compound of claim 1, wherein X is nitrogen and Y and Z are —

CH═

.

3. The compound of claim 1, wherein Y is nitrogen and X and Z are —

CH═

.

4. The compound of claim 1, wherein Z is nitrogen and X and Y are —

CH═

.

5. The compound of claim 2, wherein R¹ is hydrogen and R² and R³ are independently alkoxy.

6. The compound of claim 2, wherein R¹ is hydrogen, one of R² and R³ is alkoxy, and the other is alkyl.

7. The compound of claim 2, wherein R¹ is hydrogen, one of R² and R³ is alkoxy and the other is halo or haloalkoxy.

8. The compound of claim 3, wherein R¹ is hydrogen and R² and R³ are independently alkoxy.

9. The compound of claim 3, wherein R¹ is hydrogen, one of R² and R³ is alkoxy, and the other is alkyl.

10. The compound of claim 3, wherein R¹ is hydrogen, one of R² and R³ is alkoxy, and the other is halo or haloalkoxy.

11. The compound of claim 4, wherein R¹ is hydrogen, and R² and R³ are independently alkoxy.

12. The compound of claim 4, wherein R¹ is hydrogen, one of R² and R³is alkoxy, and the other is alkyl.

13. The compound of claim 4, wherein R¹ is hydrogen, one of R² and R³ is alkoxy and the other is halo or haloalkoxy.

14. The compound of claim 2, wherein R¹ is hydrogen, R² and R³ are independently alkoxy, and R^3a is a ring of formula:

15. The compound of claim 2, wherein R¹ is hydrogen, one of R² and R³is alkoxy and the other is alkyl, and R^3a is a ring of formula:

16. The compound of claim 2 wherein R¹ is hydrogen, one of R² and R³ is alkoxy and the other is halo or haloalkoxy, and R^3a is a ring of formula:

17. The compound of claim 3, wherein R¹ is hydrogen, R² and R³ are each independently alkoxy, and R^3a is a ring of formula:

18. The compound of claim 3, wherein R¹ is hydrogen, one of R² and R³ is alkoxy and the other is alkyl, and R^3a is a ring of formula:

19. The compound of claim 3, wherein R¹ is hydrogen, one of R² and R³ is alkoxy and the other is halo or haloalkoxy, and R^3a is a ring of formula:

20. The compound of claim 4, wherein R¹ is hydrogen, R² and R³ are each independently alkoxy, and R^3a is a ring of formula:

21. The compound of claim 4, wherein R¹ is hydrogen, one of R² and R³ is alkoxy and the other is alkyl, and R^3a is a ring of formula:

22. The compound of claim 4, wherein R¹ is hydrogen, one of R² and R³ is alkoxy and the other is halo or haloalkoxy, and R^3a is a ring of formula:

23. The compound of claim 2, wherein R¹ is hydrogen, R² and R³ are each independently alkoxy, and R^3a is a ring of formula:

24. The compound of claim 2, wherein R¹ is hydrogen, one of R² and R³ is alkoxy and the other is alkyl, and R^3a is a ring of formula:

25. The compound of claim 2, wherein R¹ is hydrogen, one of R² and R³ is alkoxy and the other is halo or haloalkoxy, and R^3a is a ring of formula:

26. The compound of claim 3, wherein R¹ is hydrogen, R² and R³ are independently alkoxy, and R^3a is a ring of formula:

27. The compound of claim 3, wherein R¹ is hydrogen, one of R² and R³ is alkoxy and the other is alkyl, and R^3a is a ring of formula:

28. The compound of claim 3, wherein R¹ is hydrogen, one of R² and R³ is alkoxy and the other is halo or haloalkoxy, and R^3a is a ring of formula:

29. The compound of claim 4, wherein R¹ is hydrogen, R² and R³ are each independently alkoxy, and R^3a is a ring of formula:

30. The compound of claim 4, wherein R¹ is hydrogen, one of R² and R³ is alkoxy and the other is alkyl, and R^3a is a ring of formula:

31. The compound of claim 4, wherein R¹ is hydrogen, one of R² and R³ is alkoxy and the other is halo or haloalkoxy, and R^3a is a ring of formula:

32. The compound of claim 1, wherein R^3a is a ring of formula:

33. The compound of claim 1, wherein R¹ is hydrogen, R² and R³ are each independently alkoxy, alkyl, haloalkoxy, or halo, and R^3a is a ring of formula:

34. The compound of claim 2, wherein R¹ is hydrogen, R² and R³ are each independently alkoxy, alkyl, haloalkoxy, or halo, and R^3a is 5-, 6-, 7-, or -8-azaindolyl or benzthiazolyl, substituted with R⁴, R⁵, or R⁶.

35. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable expicient.

36. A method of treating a disorder or disease treatable by inhibition of PDE10 enzyme in a patient which method comprises administering to the patient a pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable expicient.

37. The method of claim 36, wherein the disease is schizophrenia, bipolar disorder, or obsessive-compulsive disorder.