Morphinan compounds

• US 7,973,049 B2
• Filed: 04/30/2008
• Issued: 07/05/2011
• Est. Priority Date: 05/01/2007
• Status: Active Grant

• Current Assignee: Concert Pharmaceuticals Inc. (Sun Pharmaceutical Industries Limited)
• Original Assignee: Concert Pharmaceuticals Inc. (Sun Pharmaceutical Industries Limited)
• Inventors: Tung, Roger
• Primary Examiner(s): Aulakh; Charanjit
• Application Number:
  US12/112,936
• Publication Number:
  US 20080280936A1
• Time in Patent Office: 1,161 Days
• Field of Search: 514/289, 546/74
• US Class Current: 514/289
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/4709 Non-condensed quinolines and containing further heterocyclic rings
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/49 Cinchonan derivatives, e.g. quinine
• CPC Class Codes: A61P 11/04 for throat disorders
• CPC Class Codes: A61P 11/14 Antitussive agents
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• 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 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• 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 25/28 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 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 27/16 Otologicals
• 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 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/02 : Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 39/02 : Antidotes
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07B 59/002 : Heterocyclic compounds
• CPC Class Codes: C07D 221/28 : Morphinans
• CPC Class Codes: C07D 471/08 : Bridged systems

Abstract

This disclosure relates to novel morphinan compounds and their derivatives, pharmaceutically acceptable salts, solvates, and hydrates thereof. This disclosure also provides compositions comprising a compound of this disclosure and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering a σ₁ receptor agonist that also has NMDA antagonist activity.

Claims

1. A compound having the formula:

2. The compound or pharmaceutically acceptable salt thereof of claim 1, wherein any atom not designated as deuterium is present at its natural isotopic abundance.

3. The compound or pharmaceutically acceptable salt thereof of claim 2, wherein the pharmaceutically acceptable salt is the HBr salt.

4. A pyrogen-free composition comprising the compound or pharmaceutically acceptable salt thereof of claim 2 formulated for pharmaceutical administration and a pharmaceutically acceptable carrier.

5. The composition of claim 4, further comprising a second therapeutic agent useful in the treatment of a disease or condition selected from pseudobulbar affect and neuropathic pain.

6. The composition of claim 5, wherein the second therapeutic agent is selected from quinidine or a salt thereof, oxycodone, and gabapentin.

7. The composition of claim 6, wherein the second therapeutic agent is quinidine or a salt thereof.

8. The composition of claim 7, wherein the second therapeutic agent is quinidine sulfate.

9. The composition of claim 4 or 5, wherein the pharmaceutically acceptable salt is the HBr salt.

16. A composition according to claim 7, wherein the amount of compound is 10-60 mg and the amount of quinidine is 2.5-30 mg.

10. A method of treating a subject suffering from or susceptible to a disease or condition selected from pseudobulbar affect and neuropathic pain, comprising administering to the subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a compound having the formula:

11. The method of claim 10, wherein any atom not designated as deuterium in the compound is present at its natural isotopic abundance.

12. The method of claim 11, comprising administering to the subject in need thereof a second therapeutic agent selected from quinidine or a salt thereof, oxycodone, and gabapentin.

13. The method of claim 11, wherein the second therapeutic agent is quinidine or a salt thereof.

14. The method of claim 13, wherein the subject is suffering from or susceptible to pseudobulbar affect and the second therapeutic agent is quinidine sulfate.

15. The method of claim 11 or 12, wherein the pharmaceutically acceptable salt is the HBr salt.

17. A composition comprising a compound having the formula:

18. The composition of claim 17, wherein any atom not designated as deuterium in the compound is present at its natural isotopic abundance.

19. The composition of claim 18, further comprising a second therapeutic agent useful in the treatment of a disease or condition selected from pseudobulbar affect and neuropathic pain .

20. The composition of claim 19, wherein the second therapeutic agent is selected from quinidine or a salt thereof, oxycodone, and gabapentin.

21. The composition of claim 20, wherein the second therapeutic agent is quinidine or a salt thereof.

22. The composition of claim 21, wherein the second therapeutic agent is quinidine sulfate.

23. The composition of claim 18 or 19, wherein the pharmaceutically acceptable salt is the HBr salt.

30. A composition according to claim 21, comprising 10-60 mg of the compound and 2.5-30 mg of quinidine.

24. A method of treating a subject suffering from or susceptible to a disease or condition selected from pseudobulbar affect and neuropathic pain, comprising administering to the subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a compound having the formula:

25. The method of claim 24, wherein any atom not designated as deuterium in the compound is present at its natural isotopic abundance.

26. The method of claim 25, further comprising administering to the subject in need thereof a second therapeutic agent selected from quinidine or a salt thereof, oxycodone, and gabapentin.

27. The method of claim 26, wherein the second therapeutic agent is quinidine or a salt thereof

28. The method of claim 27, wherein the subject is suffering from or susceptible to pseudobulbar affect and the second therapeutic agent is quinidine sulfate.

29. The method of claim 25 or 26, wherein the pharmaceutically acceptable salt is the HBr salt.