DEUTERIUM-ENRICHED BOSENTAN
The present application describes deuterium-enriched bosentan, pharmaceutically acceptable salt forms thereof, and methods of treating using the same.
1 . A deuterium-enriched compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 29 are independently selected from H and D; and the abundance of deuterium in R 1 -R 29 is at least 3%.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 29 is selected from at least 3%, at least 7%, at least 14%, at least 21%, at least 28%, at least 34%, at least 41%, at least 48%, at least 55%, at least 62%, at least 69%, at least 76%, at least 83%, at least 90%, at least 97%, and 100%.
3 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 2 is selected from at least 50% and 100%.
4 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 3 -R 6 is selected from at least 25%, at least 50%, at least 75%, and 100%.
5 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 7 -R 15 is selected from at least 11%, at least 22%, at least 33%, at least 44%, at least 56%, at least 67%, at least 78%, 100%.
6 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 16 -R 19 is selected from at least 25%, at least 50%, at least 75%, and 100%.
7 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 20 -R 22 is selected from at least 33%, at least 67%, and 100%.
8 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 23 -R 26 is selected from at least 25%, at least 50%, at least 75%, and 100%.
9 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 27 -R 29 is selected from at least 33%, at least 67%, and 100%.
10 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-8 of Table 1.
11 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 9-16 of Table 2.
12 . An isolated deuterium-enriched compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 29 are independently selected from H and D; and the abundance of deuterium in R 1 -R 29 is at least 3%.
13 . An isolated deuterium-enriched compound of claim 12 , wherein the abundance of deuterium in R 1 -R 29 is selected from at least 3%, at least 7%, at least 14%, at least 21%, at least 28%, at least 34%, at least 41%, at least 48%, at least 55%, at least 62%, at least 69%, at least 76%, at least 83%, at least 90%, at least 97%, and 100%.
14 . An isolated deuterium-enriched compound of claim 12 , wherein the compound is selected from compounds 1-8 of Table 1.
15 . An isolated deuterium-enriched compound of claim 12 , wherein the compound is selected from compounds 9-16 of Table 2.
16 . A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 29 are independently selected from H and D; and the abundance of deuterium in R 1 -R 29 is at least 3%.
17 . A mixture of deuterium-enriched compound of claim 16 , wherein the compound is selected from compounds 1-8 of Table 1.
18 . A mixture of deuterium-enriched compound of claim 16 , wherein the compound is selected from compounds 9-16 of Table 2.
19 . A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt form thereof.
20 . A method for treating pulmonary artery hypertension comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt form thereof.