FUSED HETEROCYCLES

• US 20100022612A1
• Filed: 08/07/2009
• Published: 01/28/2010
• Est. Priority Date: 06/30/2006
• Status: Abandoned Application

• Current Assignee: Sepracor Incorporated
• Original Assignee: Sepracor Incorporated
• Inventors: Spear, Kerry L., Ogbu, Cyprian O., Dorsey, James M., Hopkins, Seth C., Heffernan, Michele L. R., Fang, Qun Kevin, Soukri, Mustapha, Foglesong, Robert J.
• Application Number:
  US12/537,925
• Publication Number:
  US 20100022612A1
• Time in Patent Office: Days
• US Class Current: 514/412
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• 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 25/24 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 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 491/04 Ortho-condensed systems
• CPC Class Codes: C07D 495/04 Ortho-condensed systems

Abstract

This invention provides fused heterocycles having the formula:

in which R¹ is a member selected from the group consisting of H, substituted or unsubstituted arylalkyl and substituted or unsubstituted heteroarylalkyl. R² is a member selected from the group consisting of H substituted or unsubstituted alkenyl, substituted or unsubstituted arylalkyl and substituted or unsubstituted heteroarylalkyl. R³ is a member selected from the group consisting of H, C₁-C₆ substituted or unsubstituted alkyl, substituted or unsubstituted arylalkyl and substituted or unsubstituted heteroarylalkyl. R⁴ is a member selected from OH and O⁻X⁺, in which X⁺ is positive ion which is a member selected from organic positive ions and inorganic positive ions. Substituted or unsubstituted arylalkyl and substituted or unsubstituted heteroarylalkyl moieties have the formula:

in which Ar is a member selected from the group consisting of substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. The index n is an integer from 1 to 4.

Claims

1. A method of treating pain in a subject, said method comprising administering to said subject a therapeutically effective amount of a D-amino oxidase inhibitor having the formula:

in which

R¹ is a member selected from the group consisting of H, and substituted or unsubstituted arylalkyl;

R² is a member selected from the group consisting of H, and substituted or unsubstituted arylalkyl; and

R⁴ is a member selected from OH and O⁻

X⁺

wherein

X⁺ is a positive ion which is a member selected from organic positive ions and inorganic positive ions,

wherein

substituted or unsubstituted arylalkyl has the formula;

in which

Ar is substituted or unsubstituted aryl; and

n is an integer from 1 to 4.

2. The method according to claim 1 wherein said pain is neuropathic pain.

3. The method according to claim 2 wherein said neuropathic pain in a member selected from diabetic peripheral neuropathic pain and post-herpetic neuralgia.

4. The method according to claim 1 wherein said D-amino oxidase inhibitor is administered to said subject as a pharmaceutical composition in unit dosage form comprising, per dosage unit, a pharmaceutically acceptable carrier and a daily dosage of said D-amino oxidase inhibitor in an amount from about 0.1 mg to about 7000 mg.

5. The method according to claim 4 wherein said D-amino oxidase inhibitor is present in said pharmaceutical composition in an amount of about 50 mg to about 500 mg.

6. The method according to claim 5 wherein said D-amino oxidase inhibitor is present in said pharmaceutical composition in an amount of about 1 mg to about 100 mg.

7. The method according to claim 6 wherein said D-amino oxidase inhibitor is present in said pharmaceutical composition in an amount of about 25 mg to about 50 mg.

8. The method according to claim 4 wherein said unit dosage is an oral dosage form.

9. The method according to claim 6 wherein oral dosage form is a member selected from a tablet and a capsule.

18. A method of claim 1

wherein

R¹ is H;

R² is H; and

R⁴ is a member selected from OH and O⁻

X⁺

wherein

X⁺ is a positive ion which is a member selected from organic positive ions and inorganic positive ions.

19. The method according to claim 18 wherein said pain is neuropathic pain.

20. The method according to claim 19 wherein said neuropathic pain is a member selected from diabetic peripheral neuropathic pain and post-herpetic neuralgia.

10. A method of treating pain in a subject, said method comprising administering to said subject a therapeutically effective amount of a D-amino oxidase inhibitor as a pharmaceutical composition comprising, in single or divided doses, a pharmaceutically acceptable carrier and a daily dosage of about 0.1 mg to about 7000 mg of said D-amino oxidase inhibitor, said D-amino oxidase inhibitor having the formula:

in which

R¹ is a member selected from the group consisting of H, and substituted or unsubstituted arylalkyl;

R² is a member selected from the group consisting of H, and substituted or unsubstituted arylalkyl; and

R⁴ is a member selected from OH and O⁻

X⁺

wherein

X⁺ is a positive ion which is a member selected from organic positive ions and inorganic positive ions,

wherein

substituted or unsubstituted arylalkyl has the formula;

in which

Ar is substituted or unsubstituted aryl; and

n is an integer from 1 to 4.

11. The method according to claim 10 wherein said pain is neuropathic pain.

12. The method according to claim 11 wherein said neuropathic pain in a member selected from diabetic peripheral neuropathic pain and post-herpetic neuralgia.

13. The method according to claim 10 wherein said D-amino oxidase inhibitor is present in said pharmaceutical composition in an amount of about 50 mg to about 500 mg.

14. The method according to claim 13 wherein said D-amino oxidase inhibitor is present in said pharmaceutical composition in an amount of about 1 mg to about 100 mg.

15. The method according to claim 14 wherein said D-amino oxidase inhibitor is present in said pharmaceutical composition in an amount of about 25 mg to about 50 mg.

16. The method according to claim 10 wherein said unit dosage is an oral dosage form.

17. The method according to claim 16 wherein oral dosage form is a member selected from a tablet and a capsule.