DEUTERIUM-ENRICHED VERNAKALANT
The present application describes deuterium-enriched vemakalant, 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 31 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 31 is at least 3%, provided that when (a) all of R 26 -R 31 are D; or (b) all of R 29 -R 31 are D; or (c) all of R 23 -R 25 are D; or (d) all of R 19 -R 22 are D; then at least one other R is D
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 31 is selected from at least 3%, at least 6%, at least 13%, at least 19%, at least 26%, at least 32%, at least 39%, at least 45%, at least 52%, at least 58%, at least 65%, at least 71%, at least 77%, at least 84%, at least 90%, at least 97%, and 100%.
3 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 is selected from at least 100%.
4 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 2 -R 8 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 9 -R 18 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%.
6 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-4 of Table 1.
7 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 5-8 of Table 2.
8 . An isolated deuterium-enriched compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 31 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 31 is at least 3%, provided that when (a) all of R 26 -R 31 are D; or (b) all of R 29 -R 31 are D; or (c) all of R 23 -R 25 are D; or (d) all of R 19 -R 22 are D; then at least one other R is D
9 . An isolated deuterium-enriched compound of claim 8 , wherein the abundance of deuterium in R 1 -R 31 is selected from at least 3%, at least 6%, at least 13%, at least 19%, at least 26%, at least 32%, at least 39%, at least 45%, at least 52%, at least 58%, at least 65%, at least 71%, at least 77%, at least 84%, at least 90%, at least 97%, and 100%.
10 . An isolated deuterium-enriched compound of claim 8 , wherein the abundance of deuterium in R 1 is selected from at least 100%.
11 . An isolated deuterium-enriched compound of claim 8 , wherein the abundance of deuterium in R 2 -R 8 is selected from at least 14%, at least 29%, at least 43%, at least 57%, at least 71%, at least 86%, and 100%.
12 . An isolated deuterium-enriched compound of claim 8 , wherein the abundance of deuterium in R 9 -R 18 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%.
13 . An isolated deuterium-enriched compound of claim 8 , wherein the compound is selected from compounds 1-4 of Table 1.
14 . An isolated deuterium-enriched compound of claim 8 , wherein the compound is selected from compounds 5-8 of Table 2.
15 . A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 31 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 31 is at least 3%, provided that when (a) all of R 26 -R 31 are D; or (b) all of R 29 -R 31 are D; or (c) all of R 23 -R 25 are D; or (d) all of R 19 -R 22 are D; then at least one other R is D
16 . A mixture of deuterium-enriched compound of claim 15 , wherein the abundance of deuterium in R 1 -R 31 is selected from at least 3%, at least 6%, at least 13%, at least 19%, at least 26%, at least 32%, at least 39%, at least 45%, at least 52%, at least 58%, at least 65%, at least 71%, at least 77%, at least 84%, at least 90%, at least 97%, and 100%.
17 . A mixture of deuterium-enriched compound of claim 15 , wherein the compound is selected from compounds 1-4 of Table 1.
18 . A mixture of deuterium-enriched compound of claim 15 , wherein the compound is selected from compounds 5-8 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 atrial fibrillation 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.