HETEROCYCLIC COMPOUNDS FOR THE TREATMENT OF NEUROLOGICAL AND PSYCHOLOGICAL DISORDERS

• US 20110015156A1
• Filed: 06/24/2010
• Published: 01/20/2011
• Est. Priority Date: 06/25/2009
• Status: Active Grant

• Current Assignee: Alkermes Pharma Ireland Limited (Alkermes plc)
• Original Assignee: Alkermes Pharma Ireland Limited (Alkermes plc)
• Inventors: Blumberg, Laura Cook, Zeidan, Tarek A., Remenar, Julius F.
• Granted Patent: US 8,431,576 B2
• Time in Patent Office: Days
• US Class Current: 514/82
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/497 containing further heterocyclic rings
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• 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 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 215/22 attached in position 2 or 4
• CPC Class Codes: C07D 215/227 only one oxygen atom which is attached in position 2
• CPC Class Codes: C07D 241/04 having no double bonds between ring members or between ring members and non-ring members
• CPC Class Codes: C07D 263/58 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 413/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 413/14 containing three or more hetero rings
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/14 containing three or more hetero rings
• CPC Class Codes: C07D 471/04 : Ortho-condensed systems
• CPC Class Codes: C07F 9/6558 : containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
• CPC Class Codes: C07F 9/65583 : each of the hetero rings containing nitrogen as ring hetero atom

Abstract

Lactam compounds of Formula I and their use for the treatment of neurological and psychiatric disorders including schizophrenia, bipolar disorder, anxiety disorder and insomnia is disclosed.

Claims

1. What is claimed is a compound represented by Formula I:

2. A compound of claim 1, wherein, R₁ is selected from:

3. A compound of claim 1, wherein Cy₁ is selected from:

4. A compound of claim 1, wherein R₅ is selected from:

5. A compound of claim 1, wherein R₅ is selected from:

6. A compound of claim 1 having the Formula:

7. A compound of claim 6 having the Formula:

8. A compound of claim 7 having the Formula:

9. A compound of claim 8 having the Formula:

10. A compound of claim 6 having the Formula:

11. A compound of claim 10 having the Formula:

12. A compound of claim 1 having the Formula:

13. A compound of claim 12 having the Formula:

14. A compound of claim 13 having the Formula:

15. A compound of claim 14 having the Formula:

16. A compound of claim 12 having the Formula:

17. A compound of claim 16 having the Formula:

18. A compound of claim 1, wherein R₅ is selected from Table 1, 2, 3 or 4.

19. A compound of claim 12 having the Formula:

20. A compound of claim 12 having the Formula:

21. A compound of claim 12 having the Formula:

22. A compound of claim 12 having the Formula:

23. A compound of claim 12 having the Formula:

24. A compound of claim 1 selected from Table A, B, C, D or E and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof:

25. A method of treating a neurological or psychiatric disorder by administering a compound according to claim 1 to a patient in need thereof.

26. A method according to claim 25, wherein said disorder is schizophrenia.

27. A method for sustained delivery of a compound of Formula XXIII:

28. The method of claim 27, wherein sustained release comprises a therapeutically effective amount of said compound of Formula XXIII in the blood stream of the patient for a period of at least about 36 hours after administration of the prodrug.

29. The method of claim 28, wherein said compound of Formula XXIII is present in the blood stream of the patient for a period selected from:

at least 7, 15, 30, 60, 75 or 90 days.

30. The method of claim of claim 29, wherein the administering step is by injection.

31. A method for the synthesis of a compound of Formula XXIV:

32. The process according to claim 31, wherein said aldehyde is paraformaldehyde.

33. The process according to claim 31 further comprising the step of reacting said compound of Formula XXIII with an acid anhydride.

34. The process according to claim 33, wherein said acid anhydride is selected from acetic anhydride, butyric anhydride, hexanoic anhydride, octanoic anhydride, decanoic anhydride, dodecanoic anhydride, lauric anhydride, and palmitic anhydride.