Prodrugs for the Treatment of Schizophrenia and Bipolar Disease

• US 20110166156A1
• 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:
  US12/978,274
• Publication Number:
  US 20110166156A1
• Time in Patent Office: Days
• US Class Current: 514/254.04
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: C07D 413/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 417/14 containing three or more hetero rings
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

Compounds of Formula I and Formula II 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.

Claims

1. What is claimed is a compound of formula I or II:

2. The compound of claim 1 wherein G₃ is selected from:

3. The compound of claim 1 wherein R₁ is selected from:

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

5. A compound of claim 1 wherein R₁ selected from:

6. A compound of claim 1 wherein R₁ is selected from Table 1, 2, 3, 4, or 5.

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

8. A compound according to claim 1 having the formula:

9. A method of pH-independent sustained release delivery of a parent drug to a patient comprising administering a compound according to claim 1 to a patient.

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.

19. A compound according to any of the above claims having formula:

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

14. The method according to claim 13, wherein V is selected from iodine, bromine, chlorine, hydroxynaphthoate, naphthalenedisulfonate, tosylate, triflate and mesylate.

15. The method according to claim 13, wherein said reaction is performed in a polar aprotric solvent.

16. A method for sustained delivery of a parent drug of formula XI to a patient comprising administering a prodrug compound of the parent drug having the formula I wherein the prodrug compound has lower aqueous solubility at a reference pH as compared to the aqueous solubility of the parent drug at the same reference pH wherein the reference pH is a pH at which the parent drug is fully protonated and wherein upon administration to the patient, release of the parent drug from the prodrug is sustained release.

17. A method for pH-independent sustained delivery of a parent drug of formula XI to a patient comprising administering a prodrug compound of the parent drug having the formula I wherein upon administration of said prodrug said sustained release of parent drug is substantially pH independent.

18. A method for reducing sedation in a patient compared to administration of a parent drug of formula XI comprising administering a prodrug compound of the parent drug having the formula I wherein upon administration of said prodrug, dose dumping of the drug is reduced or eliminated.