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 σ1 receptor agonist that also has NMDA antagonist activity.
1. A compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is selected from —O—(C 2 -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 1 is —O—(C 2 -C 4 )alkyl substituted with one or more deuterium atoms.
3. The compound of claim 1 or 2 , wherein R 2 is CH 3 or CD 3 .
4. The compound of claim 1 or 2 , wherein R 1 is —O—CD 2 CD 3 , —O—CD 2 CH 3 , —O—CH 2 CD 3 , —O—CD(CD 3 ) 2 , —O—CH(CD 3 ) 2 , —O—CD(CH 3 ) 2 , —O—CD 2 CH(CH 3 ) 2 , —O—CH 2 CD(CH 3 ) 2 , —O—CH 2 CH(CD 3 ) 2 , —O—CD 2 CD(CH 3 ) 2 , —O—CD 2 CH(CD 3 ) 2 , —O—CH 2 CD(CD 3 ) 2 , or —O—CD 2 CD(CD 3 ) 2 .
5. The compound of claim 4 , wherein R 1 is —O—CD 2 CD 3 , —O—CD 2 CH 3 , —O—CH 2 CD 3 , —O—CD(CD 3 ) 2 , —O—CH(CD 3 ) 2 , or —O—CD(CH 3 ) 2 .
6. The compound of claim 5 , wherein R 1 is —O—CD 2 CD 3 or —O—CD(CD 3 ) 2 .
7. The compound of claim 6 , wherein R 1 is —O—CD(CD 3 ) 2 .
8. The compound of claim 3 , wherein the compound is selected from any one of the compounds set forth in the table below:
Compound No.
R 1
R 2
100
—O—CD 2 CD 3
CD 3
101
—O—CD 2 CH 3
CD 3
102
—O—CD(CD 3 ) 2
CD 3
103
—O—CD(CH 3 ) 2
CD 3
104
—O—CD 2 CD 3
CH 3
105
—O—CD 2 CH 3
CH 3
106
—O—CD(CD 3 ) 2
CH 3
107
—O—CD(CH 3 ) 2
CH 3
or a pharmaceutically acceptable salt thereof.
9. The compound of any one of claims 1 - 2 , 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 , further comprising a second therapeutic agent useful in treating a patient suffering from or susceptible to pain.
12. The composition of claim 10 , further comprising a second therapeutic agent useful in treating a patient suffering from or susceptible to conditions related to exposure to chemical agents.
13. A compound having the structure:
or a pharmaceutically acceptable salt thereof, wherein any atom not designated as deuterium is present at its natural isotopic abundance.
14. A compound having the structure:
or a pharmaceutically acceptable salt thereof, wherein any atom not designated as deuterium is present at its natural isotopic abundance.
15. A compound having the structure:
or a pharmaceutically acceptable salt thereof, wherein any atom not designated as deuterium is present at its natural isotopic abundance.