Morphinan compounds
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.
1. 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 .
2. The compound of claim 1 , wherein R 2 is CH 3 or CD 3 .
3. The compound of claim 1 , wherein R 1 is —CH 3 , —CD 3 , —CH 2 CH 3 , —CD 2 CD 3 , —CD 2 CH 3 , —CH 2 CD 3 , —CH(CH 3 ) 2 , —CD(CD 3 ) 2 , —CH(CD 3 ) 2 , —CD(CH 3 ) 2 , —CH 2 CH(CH 3 ) 2 , —CD 2 CH(CH 3 ) 2 , —CH 2 CD(CH 3 ) 2 , —CH 2 CH(CD 3 ) 2 , —CD 2 CD(CH 3 ) 2 , —CD 2 CH(CD 3 ) 2 , —CH 2 CD(CD 3 ) 2 , or —CD 2 CD(CD 3 ) 2 .
4. The compound of claim 3 , wherein R 1 is —CD 3 , —CD 2 CD 3 , —CD 2 CH 3 , —CH 2 CD 3 , —CD(CD 3 ) 2 , —CH(CD 3 ) 2 , —CD(CH 3 ) 2 , —CD 2 CH(CH 3 ) 2 , —CH 2 CD(CH 3 ) 2 , —CH 2 CH(CD 3 ) 2 , —CD 2 CD(CH 3 ) 2 , —CD 2 CH(CD 3 ) 2 , —CH 2 CD(CD 3 ) 2 , or —CD 2 CD(CD 3 ) 2 .
5. The compound of claim 4 , wherein R 1 is —CD 3 , —CD 2 CD 3 , or —CD 2 CD(CD 3 ) 2 .
6. The compound of claim 5 , wherein R 1 is —CD 3 .
7. The compound of claim 3 , wherein R 1 is —CH 3 , —CH 2 CH 3 , —CH(CH 3 ) 2 , or —CH 2 CH(CH 3 ) 2 and R 2 is selected from CD 3 .
8. The compound of claim 1 , wherein any atom not designated as deuterium is present at its natural isotopic abundance.
9. The compound of claim 3 , selected from any one of:
or a pharmaceutically acceptable salt thereof, wherein any atom not designated as deuterium is present at its natural isotopic abundance.
10. A pyrogen-free pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
11. The composition of claim 10 , wherein the second therapeutic agent is selected from quinidine, quinidine sulfate, oxycodone, and gabapentin.
12. The compound of claim 1 , wherein deuterium incorporation at any atom designated as deuterium is at least 90%.
13. The compound of claim 12 , wherein deuterium incorporation at any atom designated as deuterium is at least 95%.
14. The compound of claim 9 , wherein deuterium incorporation at any atom designated as deuterium is at least 90%.
15. The compound of claim 14 , wherein deuterium incorporation at any atom designated as deuterium is at least 95%.