Deuterated compounds as rock inhibitors
Provided are compounds of Formula (I), or pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising these compounds thereof, and use of these compounds in preparing drugs for inhibiting ROCK.
1. A compound of formula (I):
or a pharmaceutically acceptable salt thereof, wherein
R 1 is selected from CH 3 , CH 2 D, CHD 2 and CD 3 ;
R 2 is selected from CH 3 , CH 2 D, CHD 2 and CD 3 ;
Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , Y 7 , Y 9 , Y 10 , Y 11 , Y 12 , Y 14 , Y 15 and Y 16 are each independently selected from hydrogen and deuterium;
each Y 8 is independently selected from hydrogen and deuterium, provided that both Y 8 are the same;
each Y 13 is independently selected from hydrogen and deuterium, provided that both Y 13 are the same;
provided that the compound of formula (I) contains at least one deuterium atom.
2. The compound of claim 1 or the pharmaceutically acceptable salt thereof, wherein Y 1 is deuterium.
3. The compound of claim 1 or the pharmaceutically acceptable salt thereof, wherein Y 2 is deuterium.
4. The compound of claim 1 or the pharmaceutically acceptable salt thereof, wherein Y 3 is deuterium.
5. The compound of claim 1 or the pharmaceutically acceptable salt thereof, wherein Y 7 is deuterium.
6. The compound of claim 1 or the pharmaceutically acceptable salt thereof, wherein both Y 8 are deuterium.
7. The compound of claim 1 or the pharmaceutically acceptable salt thereof, wherein both Y 13 are deuterium.
8. The compound of claim 1 or the pharmaceutically acceptable salt thereof, wherein R 1 is selected from CH 3 and CD 3 .
9. The compound of claim 1 or the pharmaceutically acceptable salt thereof, wherein R 2 is selected from CH 3 and CD 3 .
10. The compound of claim 1 , selected from
and pharmaceutically acceptable salts thereof.
11. The compound of claim 10 or the pharmaceutically acceptable salt thereof, selected from
and pharmaceutically acceptable salts thereof.
12. The compound of claim 11 or the pharmaceutically acceptable salt thereof, selected from
and pharmaceutically acceptable salts thereof.
13. The compound of claim 1 or the pharmaceutically acceptable salt thereof, wherein the pharmaceutically acceptable salt thereof is hydrochloride.
14. The compound of claim 13 or the pharmaceutically acceptable salt thereof, wherein the pharmaceutically acceptable salt thereof is dihydrochloride.
15. A pharmaceutical composition, comprising the compound of claim 1 or the pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable carrier.
16. A method of treating, ameliorating or preventing a condition, which responds to inhibition of ROCK, comprising administering to a subject in need of such treatment an effective amount of the compound of claim 1 , or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition thereof, and optionally in combination with a second therapeutic agent.
17. A method of treating elevate intraocular pressure, comprising administering to a subject in need of such treatment an effective amount of the compound of claim 1 or the pharmaceutically acceptable salt thereof.
18. A pharmaceutical composition, comprising the compound of claim 10 or the pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable carrier.
19. A method of treating, ameliorating or preventing a condition, which responds to inhibition of ROCK, comprising administering to a subject in need of such treatment an effective amount of the compound of claim 10 , or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition thereof, and optionally in combination with a second therapeutic agent.
20. A method of treating elevated intraocular pressure, comprising administering to a subject in need of such treatment an effective amount of the compound of claim 10 or the pharmaceutically acceptable salt thereof.