Morphinan compounds

Patent metadata

Field	Value
Publication number	US-10022370-B2
Application number	US-201715488064-A
Country	US
Kind code	B2
Filing date	Apr 14, 2017
Priority date	Sep 19, 2008
Publication date	Jul 17, 2018
Grant date	Jul 17, 2018

Abstract

This invention relates to novel morphinan compounds and pharmaceutically acceptable salts thereof. This invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering a σ 1 receptor agonist that also has NMDA antagonist activity.

First claim

We claim:

1. A method of treating a subject suffering from or susceptible to intractable coughing, comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:
R 1 is —(C 1 -C 4 )alkyl, wherein R 1 is optionally substituted with one or more deuterium atoms; and
R 2 is selected from CH 3 , CH 2 D, CHD 2 , and CD 3 ;
provided that at least one deuterium atom is present at either R 1 or R 2 ;
wherein any atom not designated as deuterium is present at its natural isotopic abundance; and
wherein the amount of the compound administered is in the range from 4.0 mg to 350 mg.

2. The method of claim 1 , wherein the amount of the compound administered is in the range from 10 mg to 90 mg.

3. The method of claim 1 , wherein the amount of the compound administered is in the range from 30 mg to 45 mg.

4. The method of claim 1 , wherein the compound is administered once daily.

5. The method of claim 1 , wherein the compound is administered twice daily.

6. The method of claim 1 , wherein the compound is selected from any one of:

or a pharmaceutically acceptable salt thereof.

7. The method of claim 1 , wherein the deuterium incorporation at each designated deuterium atom is at least 90%.

8. The method of claim 1 , wherein the deuterium incorporation at each designated deuterium atom is at least 95%.

9. A compound selected from:

wherein the (C 1 -C 4 alkyl) is deuterated.

10. The compound of claim 9 , wherein the deuterium incorporation at each designated deuterium atom is at least 90%.

11. The compound of claim 9 , wherein the deuterium incorporation at each designated deuterium atom is at least 95%.

12. A method of treating a subject suffering from or susceptible to a disease or condition selected from neurological disorders and neurodegenerative diseases, diabetic neuropathy, neuropathic pain, epileptic seizures, and methotrexate neurotoxicity, comprising the step of administering to the subject in need thereof a therapeutically effective amount of a compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:
R 1 is —(C 1 -C 4 )alkyl, wherein R 1 is optionally substituted with one or more deuterium atoms; and
R 2 is selected from CH 3 , CH 2 D, CHD 2 , and CD 3 ;
provided that at least one deuterium atom is present at either R 1 or R 2 ;
wherein any atom not designated as deuterium is present at its natural isotopic abundance; and
wherein the amount of the compound administered is in the range from 0.4 mg to 400 mg.

13. The method of claim 12 , wherein the amount of the compound administered is in the range from 4.0 mg to 350 mg.

14. The method of claim 12 , wherein the amount of the compound administered is in the range from 10 mg to 90 mg.

15. The method of claim 12 , wherein the amount of the compound administered is in the range from 30 mg to 45 mg.

16. The method of claim 12 , wherein the compound is administered once daily.

17. The method of claim 12 , wherein the compound is administered twice daily.

18. The method of claim 12 , wherein the neurological disorders and neurodegenerative diseases are selected from dementia, amyotrophic lateral sclerosis (ALS), Alzheimer's disease, and multiple sclerosis.

19. The method of claim 12 , wherein the disease or condition is epileptic seizures.

20. The method of claim 12 , wherein the deuterium incorporation at each designated deuterium atom is at least 90%.

21. The method of claim 12 , wherein the deuterium incorporation at each designated deuterium atom is at least 95%.

Assignees

• Concert Pharmaceuticals Inc

Inventors

• Graham Philip B
• Silverman I Robert

Classifications

• A61K31/195

  having an amino group · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title

• C07B59/002

  Heterocyclic compounds · CPC title

• C07D471/08

  Bridged systems · CPC title

• C07D221/28 Primary

  Morphinans · CPC title