Endothelin receptor antagonists
View Patent ↗This invention relates to novel endothelin receptor antagonists, derivatives, acceptable acid addition salts thereof. The 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 compounds that block the endothelin signaling pathway that leads to vasoconstriction and in particular those diseases or conditions beneficially treated by endothelin receptor antagonists.
1. A compound of the formula (I):
or a pharmaceutically acceptable salt thereof, wherein:
each Y is independently selected from hydrogen or deuterium, and Y 2a is additionally selected from OH;
each Z is independently selected from hydrogen, deuterium, or fluorine; and
at least one Y or Z is deuterium.
2. The compound according to claim 1 , wherein each Y 1 is the same.
3. The compound of claim 2 wherein each Y 1 is simultaneously deuterium.
4. The compound of claim 2 wherein each Y 1 is simultaneously hydrogen.
5. The compound according to claim 1 , wherein Y 2b , Y 2c Y 2d , Y 2e , Y 2f , Y 2g , Y 2h , and Y 2i are the same.
6. The compound of claim 5 , wherein Y 2a , Y 2b , Y 2c Y 2d , Y 2e , Y 2f , Y 2g , Y 2h , and Y 2i are the same.
7. The compound of claim 5 , wherein Y 2a is OH.
8. The compound of claim 5 , wherein Y 2b , Y 2c Y 2d , Y e , Y 2f , Y 2g , Y 2h , and Y 2i are simultaneously deuterium.
9. The compound of claim 5 , wherein Y 2b , Y 2c Y 2d , Y 2e , Y 2f , Y 2g , Y 2h , and Y 2i are simultaneously hydrogen.
10. The compound according to claim 1 , wherein Z 1a and Z 1b are simultaneously deuterium.
11. The compound according to claim 1 , wherein Z 1a and Z 1b are simultaneously hydrogen.
12. The compound according to claim 1 , wherein Z 1a and Z 1b are simultaneously fluorine.
13. The compound of claim 1 , wherein the compound is selected from any one of the compounds below:
or a pharmaceutically acceptable salt thereof.
14. The compound according to claim 1 , wherein any atom not specified as deuterium is present in its natural isotopic abundance.
15. A compound selected from:
16. A compound of claim 15 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
17. A compound selected from any one of:
each Y is independently selected from hydrogen or deuterium, and Y 2a is additionally selected from OH;
each Z is independently selected from hydrogen, deuterium, or fluorine; and
at least one Y or Z is deuterium.
18. The compound of claim 17 , wherein the compound has the formula:
19. A pharmaceutical composition comprising a compound of claim 1 ; and a pharmaceutically acceptable carrier.