Inhibitors of D-amino acid oxidase

• US 7,902,252 B2
• Filed: 07/20/2009
• Issued: 03/08/2011
• Est. Priority Date: 01/18/2007
• Status: Active Grant

• Current Assignee: Sunovion Pharmaceuticals Inc. (Sumitomo Chemical Company Limited)
• Original Assignee: Sepracor Incorporated (Sumitomo Chemical Company Limited)
• Inventors: Spear, Kerry L., Ogbu, Cyprian O., Hopkins, Seth C., Heffernan, Michele L. R., Fang, Qun Kevin, Soukri, Mustapha, Foglesong, Robert J.
• Primary Examiner(s): Chung; Susannah
• Assistant Examiner(s): Coppins; Janet L
• Application Number:
  US12/506,204
• Publication Number:
  US 20100029737A1
• Time in Patent Office: 596 Days
• Field of Search: 548/531, 514/423
• US Class Current: 514/423
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: C07D 209/42 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 209/52 condensed with a ring other than six-membered
• CPC Class Codes: C07D 209/94 containing carbocyclic rings other than six-membered
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C07D 491/04 Ortho-condensed systems
• CPC Class Codes: C07D 495/04 Ortho-condensed systems

Abstract

The present invention provides novel inhibitors of the enzyme D-amino acid oxidase. The compounds of the invention are useful for treating or preventing diseases and/or condition, wherein modulation of D-serine levels, and/or its oxidative products, is effective in ameliorating symptoms. The invention further provides methods of enhancing learning, memory and/or cognition. For example, the invention provides methods for treating or preventing loss of memory and/or cognition associated with neurodegenerative diseases, such as Alzheimer'"'"'s disease. The invention further provides methods for preventing loss of neuronal function characteristic of neurodegenerative diseases. In addition, methods are provided for the treatment or prevention of neuropsychiatric diseases (e.g., schizophrenia) and for the treatment or prevention of pain and ataxia.

Claims

1. A compound having a structure according to Formula (Vc):

2. A composition comprising a first stereoisomer and at least one additional stereoisomer of a compound according to claim 1, wherein said first stereoisomer is present in an enantiomeric or diastereomeric excess of at least 90% relative to said at least one additional stereoisomer.

3. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

4. A compound having a structure according to Formula (IVc):

5. A composition comprising a first stereoisomer and at least one additional stereoisomer of a compound according to claim 4, wherein said first stereoisomer is present in an enantiomeric or diastereomeric excess of at least 90% relative to said at least one additional stereoisomer.

6. A pharmaceutical composition comprising a compound of claim 4, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

7. A compound having a structure according to Formula (VIIb):

8. A composition comprising a first stereoisomer and at least one additional stereoisomer of a compound according to claim 7, wherein said first stereoisomer is present in an enantiomeric or diastereomeric excess of at least 90% relative to said at least one additional stereoisomer.

9. A pharmaceutical composition comprising a compound of claim 7, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

10. A compound having a structure according to Formula (VIIIb):

11. A composition comprising a first stereoisomer and at least one additional stereoisomer of a compound according to claim 10, wherein said first stereoisomer is present in an enantiomeric or diastereomeric excess of at least 90% relative to said at least one additional stereoisomer.

12. A pharmaceutical composition comprising a compound of claim 10, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.