DEUTERIUM-ENRICHED HYDROMORPHONE
The present application describes deuterium-enriched hydromorphone, 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 19 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 19 is at least 5%.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 19 is selected from at least 5%, at least 11%, at least 16%, at least 21%, at least 26%, at least 32%, at least 37%, at least 42%, at least 47%, at least 53%, at least 58%, (k) at least 63%, at least 68%, at least 74%, at least 79%, at least 84%, at least 89%, at least 95%, 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 10 -R 12 is selected from at least 33%, at least 67%, and 100%.
5 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 and R 10 -R 12 is selected from at least 25%, at least 50%, at least 75%, and 100%.
6 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 2 -R 3 is selected from at least 50% and 100%.
7 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 4 -R 12 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%.
8 . 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%.
9 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 17 -R 19 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 19 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 19 is at least 5%.
13 . An isolated deuterium-enriched compound of claim 12 , wherein the abundance of deuterium in R 1 -R 19 is selected from at least 5%, at least 11%, at least 16%, at least 21%, at least 26%, at least 32%, at least 37%, at least 42%, at least 47%, at least 53%, at least 58%, (k) at least 63%, at least 68%, at least 74%, at least 79%, at least 84%, at least 89%, at least 95%, 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 19 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 19 is at least 5%.
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 pain 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.