DEUTERIUM-ENRICHED FINGOLIMOD
The present application describes deuterium-enriched fingolimod, 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 33 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 33 is at least 3%.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 33 is selected from at least 3%, at least 6%, at least 12%, at least 18%, at least 24%, at least 30%, at least 36%, at least 42%, at least 48%, at least 55%, at least 61%, at least 67%, at least 73%, at least 79%, at least 85%, at least 91%, at least 94%, and 100%.
3 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 4 is selected from at least 25%, at least 50%, at least 75%, and 100%.
4 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 13 -R 16 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 1 -R 4 and R 13 -R 16 is selected from at least 13%, at least 25%, at least 38%, at least 50%, at least 63%, at least 75%, at least 88%, and 100%.
6 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 5 -R 12 is selected from at least 13%, at least 25%, at least 38%, at least 50%, at least 63%, at least 75%, at least 88%, and 100%.
7 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 17 -R 33 is selected from at least 6%, at least 12%, at least 18%, at least 24%, at least 29%, at least 35%, at least 41%, at least 47%, at least 53%, at least 59%, at least 65%, at least 71%, at least 76%, at least 82%, at least 88%, at least 94%, and 100%.
8 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-6 of Table 1.
9 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 7-12 of Table 2.
10 . An isolated deuterium-enriched compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 33 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 33 is at least 3%.
11 . An isolated deuterium-enriched compound of claim 10 , wherein the abundance of deuterium in R 1 -R 33 is selected from at least 3%, at least 6%, at least 12%, at least 18%, at least 24%, at least 30%, at least 36%, at least 42%, at least 48%, at least 55%, at least 61%, at least 67%, at least 73%, at least 79%, at least 85%, at least 91%, at least 94%, and 100%.
12 . An isolated deuterium-enriched compound of claim 10 , wherein the abundance of deuterium in R 1 -R 4 is selected from at least 25%, at least 50%, at least 75%, and 100%.
13 . An isolated deuterium-enriched compound of claim 10 , wherein the abundance of deuterium in R 13 -R 16 is selected from at least 25%, at least 50%, at least 75%, and 100%.
14 . An isolated deuterium-enriched compound of claim 10 , wherein the compound is selected from compounds 1-6 of Table 1.
15 . An isolated deuterium-enriched compound of claim 10 , wherein the compound is selected from compounds 7-12 of Table 2.
16 . A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 33 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 33 is at least 3%.
17 . A mixture of deuterium-enriched compound of claim 16 , wherein the compound is selected from compounds 1-6 of Table 1.
18 . A mixture of deuterium-enriched compound of claim 16 , wherein the compound is selected from compounds 7-12 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 multiple sclerosis 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.