Deuterated aminocyclohexyl ether compounds and processes for preparing same
This invention is directed to deuterated aminocyclohexyl ether compounds and processes for preparing same and methods of using same.
1. A compound of formula (I):
wherein:
R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 11 , R 12 , R 13 , R 14 , R 15 and R 16 are each independently hydrogen or deuterium; and
R 9 and R 10 are each independently hydroxy, methoxy or —OCD 3 ;
where at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 11 , R 12 , R 13 , R 14 , R 15 and R 16 is deuterium or at least one of R 9 and R 10 is —OCD 3 ;
or an isolated stereoisomer thereof;
or a pharmaceutically acceptable salt thereof;
wherein the deuterium present in the compound is present at greater than the natural abundance of deuterium.
2. The compound of claim 1 wherein:
R 1 and R 2 are both hydrogen or are both deuterium;
R 3 and R 4 are both hydrogen or are both deuterium;
R 5 and R 6 are both hydrogen or are both deuterium;
R 7 and R 8 are both hydrogen or are both deuterium;
R 9 and R 10 are each independently hydroxy, methoxy or —OCD 3 ;
R 11 is hydrogen or deuterium;
R 12 and R 13 are both hydrogen or are both deuterium; and
R 14 , R 15 , and R 16 are all hydrogen or all deuterium.
3. The compound of claim 1 wherein:
R 1 and R 2 are both hydrogen or are both deuterium;
R 3 and R 4 are both hydrogen or are both deuterium;
R 5 and R 6 are both deuterium;
R 7 and R 8 are both hydrogen or are both deuterium;
R 9 and R 10 are each independently hydroxy, methoxy or —OCD 3 ;
R 11 is hydrogen or deuterium;
R 12 and R 13 are both hydrogen or are both deuterium; and
R 14 , R 15 , and R 16 are all hydrogen or all deuterium.
4. The compound of claim 1 wherein:
R 1 and R 2 are both hydrogen or are both deuterium;
R 3 and R 4 are both hydrogen or are both deuterium;
R 5 and R 6 are both hydrogen or are both deuterium;
R 7 and R 8 are both deuterium;
R 9 and R 10 are each independently hydroxy, methoxy or —OCD 3 ;
R 11 is hydrogen or deuterium;
R 12 and R 13 are both hydrogen or are both deuterium; and
R 14 , R 15 , and R 16 are all hydrogen or all deuterium.
5. The compound of claim 1 wherein:
R 1 and R 2 are both deuterium;
R 3 and R 4 are both deuterium;
R 5 and R 6 are both hydrogen or are both deuterium;
R 7 and R 8 are both hydrogen or are both deuterium;
R 9 and R 10 are each independently hydroxy, methoxy or —OCD 3 ;
R 11 is hydrogen or deuterium;
R 12 and R 13 are both hydrogen or are both deuterium; and
R 14 , R 15 , and R 16 are all hydrogen or all deuterium.
6. The compound of claim 1 wherein:
R 1 and R 2 are both hydrogen or are both deuterium;
R 3 and R 4 are both hydrogen or are both deuterium;
R 5 and R 6 are both hydrogen or are both deuterium;
R 7 and R 8 are both hydrogen or are both deuterium;
R 9 is —OCD 3 ;
R 10 is hydroxy, methoxy or —OCD 3 ;
R 11 is hydrogen or deuterium;
R 12 and R 13 are both hydrogen or are both deuterium; and
R 14 , R 15 , and R 16 are all hydrogen or all deuterium.
7. The compound of claim 1 wherein:
R 1 and R 2 are both hydrogen or are both deuterium;
R 3 and R 4 are both hydrogen or are both deuterium;
R 5 and R 6 are both hydrogen or are both deuterium;
R 7 and R 8 are both hydrogen or are both deuterium;
R 9 is hydroxy, methoxy or —OCD 3 ;
R 10 is —OCD 3 ;
R 11 is hydrogen or deuterium;
R 12 and R 13 are both hydrogen or are both deuterium; and
R 14 , R 15 , and R 16 are all hydrogen or all deuterium.
8. The compound of claim 1 wherein:
R 1 and R 2 are both hydrogen or are both deuterium;
R 3 and R 4 are both hydrogen or are both deuterium;
R 5 and R 6 are both hydrogen or are both deuterium;
R 7 and R 8 are both hydrogen or are both deuterium;
R 9 and R 10 are each independently hydroxy, methoxy or —OCD 3 ;
R 11 is deuterium;
R 12 and R 13 are both hydrogen or are both deuterium; and
R 14 , R 15 , and R 16 are all hydrogen or all deuterium.
9. The compound of claim 1 wherein:
R 1 and R 2 are both hydrogen or are both deuterium;
R 3 and R 4 are both hydrogen or are both deuterium;
R 5 and R 6 are both hydrogen or are both deuterium;
R 7 and R 8 are both hydrogen or are both deuterium;
R 9 and R 10 are each independently hydroxy, methoxy or —OCD 3 ;
R 11 is hydrogen or deuterium;
R 12 and R 13 are both deuterium; and
R 14 , R 15 , and R 16 are all hydrogen or all deuterium.
10. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula (I):
wherein:
R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 11 , R 12 , R 13 , R 14 , R 15 and R 16 are each independently hydrogen or deuterium; and
R 9 and R 10 are each independently hydroxy, methoxy or —OCD 3 ;
where at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 11 , R 12 , R 13 , R 14 , R 15 and R 16 is deuterium or at least one of R 9 and R 10 is —OCD 3 ;
or an isolated stereoisomer thereof;
or a pharmaceutically acceptable salt thereof;
wherein the deuterium present in the compound is present at greater than the natural abundance of deuterium.
11. A compound of formula (II):
wherein:
R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 11 , R 12 and R 13 are each independently hydrogen or deuterium; and
R 9 and R 10 are each independently hydroxy, methoxy or —OCD 3 ;
where at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 11 , R 12 and R 13 is deuterium or at least one of R 9 and R 10 is —OCD 3 ;
or an isolated stereoisomer thereof;
or a pharmaceutically acceptable salt thereof;
wherein the deuterium present in the compound is present at greater than the natural abundance of deuterium.
12. The compound of claim 11 wherein:
R 1 and R 2 are both hydrogen or are both deuterium;
R 3 and R 4 are both hydrogen or are both deuterium;
R 5 and R 6 are both hydrogen or are both deuterium;
R 7 and R 8 are both hydrogen or are both deuterium;
R 9 and R 10 are each independently hydroxy, methoxy or —OCD 3 ;
R 11 is hydrogen or deuterium; and
R 12 and R 13 are both hydrogen or are both deuterium.
13. The compound of claim 11 wherein:
R 1 and R 2 are both hydrogen or are both deuterium;
R 3 and R 4 are both hydrogen or are both deuterium;
R 5 and R 6 are both deuterium;
R 7 and R 8 are both hydrogen or are both deuterium;
R 9 and R 10 are each independently hydroxy, methoxy or —OCD 3 ;
R 11 is hydrogen or deuterium; and
R 12 and R 13 are both hydrogen or are both deuterium.
14. The compound of claim 11 wherein:
R 1 and R 2 are both hydrogen or are both deuterium;
R 3 and R 4 are both hydrogen or are both deuterium;
R 5 and R 6 are both hydrogen or are both deuterium;
R 7 and R 8 are both deuterium;
R 9 and R 10 are each independently hydroxy, methoxy or —OCD 3 ;
R 11 is hydrogen or deuterium; and
R 12 and R 13 are both hydrogen or are both deuterium.
15. The compound of claim 11 wherein:
R 1 and R 2 are both deuterium;
R 3 and R 4 are both deuterium;
R 5 and R 6 are both hydrogen or are both deuterium;
R 7 and R 8 are both hydrogen or are both deuterium;
R 9 and R 10 are each independently hydroxy, methoxy or —OCD 3 ;
R 11 is hydrogen or deuterium; and
R 12 and R 13 are both hydrogen or are both deuterium.
16. The compound of claim 11 wherein:
R 1 and R 2 are both hydrogen or are both deuterium;
R 3 and R 4 are both hydrogen or are both deuterium;
R 5 and R 6 are both hydrogen or are both deuterium;
R 7 and R 8 are both hydrogen or are both deuterium;
R 9 is —OCD 3 ;
R 10 is hydroxy, methoxy or —OCD 3 ;
R 11 is hydrogen or deuterium; and
R 12 and R 13 are both hydrogen or are both deuterium.
17. The compound of claim 11 wherein:
R 1 and R 2 are both hydrogen or are both deuterium;
R 3 and R 4 are both hydrogen or are both deuterium;
R 5 and R 6 are both hydrogen or are both deuterium;
R 7 and R 8 are both hydrogen or are both deuterium;
R 9 is hydroxy, methoxy or —OCD 3 ;
R 10 is —OCD 3 ;
R 11 is hydrogen or deuterium; and
R 12 and R 13 are both hydrogen or are both deuterium.
18. The compound of claim 11 wherein:
R 1 and R 2 are both hydrogen or are both deuterium;
R 3 and R 4 are both hydrogen or are both deuterium;
R 5 and R 6 are both hydrogen or are both deuterium;
R 7 and R 8 are both hydrogen or are both deuterium;
R 9 and R 10 are each independently hydroxy, methoxy or —OCD 3 ;
R 11 is deuterium; and
R 12 and R 13 are both hydrogen or are both deuterium.
19. The compound of claim 11 wherein:
R 1 and R 2 are both hydrogen or are both deuterium;
R 3 and R 4 are both hydrogen or are both deuterium;
R 5 and R 6 are both hydrogen or are both deuterium;
R 7 and R 8 are both hydrogen or are both deuterium;
R 9 and R 10 are each independently hydroxy, methoxy or —OCD 3 ;
R 11 is hydrogen or deuterium; and
R 12 and R 13 are both deuterium.
20. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula (II):
wherein:
R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 11 , R 12 and R 13 are each independently hydrogen or deuterium; and
R 9 and R 10 are each independently hydroxy, methoxy or —OCD 3 ;
where at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 11 , R 12 and R 13 is deuterium or at least one of R 9 and R 10 is —OCD 3 ;
or an isolated stereoisomer thereof;
or a pharmaceutically acceptable salt thereof;
wherein the deuterium present in the compound is present at greater than the natural abundance of deuterium.