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 method of treating arrhythmia in a human, wherein the method comprises administering to the human in need thereof a therapeutically effective amount of 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 method 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 method 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 method 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 method 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 method 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 method 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 method 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 method 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 method of treating arrhythmia in a human, wherein the method comprises administering to the human in need thereof a therapeutically effective amount of 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 , 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.