Asenapine Prodrugs

• US 20110166194A1
• Filed: 12/23/2010
• Published: 07/07/2011
• Est. Priority Date: 01/07/2010
• Status: Abandoned Application

• Current Assignee: Alkermes Pharma Ireland Limited (Alkermes plc)
• Original Assignee: Alkermes Pharma Ireland Limited (Alkermes plc)
• Inventors: Almarsson, Örn, Blumberg, Laura Cook
• Application Number:
  US12/978,298
• Publication Number:
  US 20110166194A1
• Time in Patent Office: Days
• US Class Current: 514/410
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: C07D 491/044 with only one oxygen atom as ring hetero atom in the oxygen-containing ring

Abstract

Compounds of Formula I and their use for the treatment of neurological and psychiatric disorders including schizophrenia and manic or mixed episodes associated with bipolar I disorder with or without psychotic features is disclosed:

wherein R₁-R₈, G, N and A⁻ are as defined in the written description.

Claims

1. A compound represented by Formula I:

2. A compound according to claim 1 represented by Formula II:

3. A compound of claim 1, wherein R₅ 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, wherein R₅ is selected from Table 1, 2, 3, 4 or 5.

7. A compound of claim 1 selected from Table A.

8. A compound of claim 1 selected from:

9. A compound according to claim 1, wherein the relative stereochemistry between the two pyrrolidine ring fusion centers is trans.

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

11. A method according to claim 10, wherein said disorder is schizophrenia.

12. A method according to claim 10, wherein said disorder bipolar I disorder.

15. A method of pH-independent sustained release delivery of asenapine to a patient comprising administering to the patient a compound according to claim 1.

16. A method of reducing sedation in a patient comprising administering to the patient a compound according to claim 1.

13. A method for the synthesis of a compound of formula I:

14. The process according to claim 13, wherein V is iodo, bromo, or chloro, and said reaction is performed in an aprotic solvent.