DEUTERIUM-ENRICHED ATRASENTAN
The present application describes deuterium-enriched atrasentan, 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 38 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 38 is at least 3%.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 38 is selected from at least 3%, at least 8%, at least 12%, at least 16%, at least 20%, at least 23%, at least 28%, at least 32%, at least 36%, at least 40%, at least 43%, at least 48%, at least 52%, at least 56%, at least 60%, at least 63%, at least 68%, at least 72%, at least 76%, at least 80%, at least 83%, at least 88%, at least 92%, at least 96%, and 100%.
3 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 9 , R 18 , and R 19 is selected from at least 33%, at least 67%, and 100%.
4 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 3 -R 5 , and R 1 -R 14 is selected from at least 14%, at least 29%, at least 43%, at least 57%, at least 71%, at least 86%, and 100%.
5 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 2 , R 6 -R 8 , R 10 , R 15 -R 17 , R 20 , and R 37 is selected from at least 9%, 18%, at least 27%, at least 36%, at least 45%, at least 56%, at least 64%, at least 73%, at least 82%, at least 91%, and 100%.
6 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 3 -R 5 , R 9 , R 11 -R 14 , R 18 , R 19 is selected from at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, and 100%.
7 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 2 , R 6 -R 8 , R 9 , R 10 , R 15 -R 17 , R 18 , R 19 , R 20 , and R 37 is selected from at least 7%, at least 14%, at least 21%, at least 29%, at least 36%, at least 43%, at least 50%, at least 57%, at least 64%, at least 71%, at least 79%, at least 86%, at least 93%, and 100%.
8 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 2 , R 3 -R 5 , R 6 -R 8 , R 10 , R 11 -R 14 , R 15 -R 17 , R 20 , and R 37 is selected from at least 6% , at least 11%, at least 17%, at least 22%, at least 28%, at least 33%, at least 39%, at least 44%, at least 50%, at least 56%, at least 61%, at least 67%, at least 72%, at least 78%, at least 83%, at least 89%, at least 94%, and 100%.
9 . 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%.
10 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 15 -R 17 is selected from at least 33%, at least 67%, and 100%.
11 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 20 -R 37 is selected from at least 6% , at least 11%, at least 17%, at least 22%, at least 28%, at least 33%, at least 39%, at least 44%, at least 50%, at least 56%, at least 61%, at least 67%, at least 72%, at least 78%, at least 83%, at least 89%, at least 94%, and 100%.
12 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-10 of Table 1.
13 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 11-20 of Table 2.
14 . An isolated deuterium-enriched compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 38 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 38 is at least 3%.
15 . An isolated deuterium-enriched compound of claim 14 , wherein the compound is selected from compounds 1-10 of Table 1.
16 . An isolated deuterium-enriched compound of claim 14 , wherein the compound is selected from compounds 11-20 of Table 2.
17 . A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 38 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 38 is at least 3%.
18 . A mixture of deuterium-enriched compounds of claim 17 , wherein the compounds are selected from compounds 1-10 of Table 1.
19 . A mixture of deuterium-enriched compounds of claim 17 , wherein the compounds are selected from compounds 11-20 of Table 2.
20 . 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.
21 . A method for treating prostate cancer 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.