DEUTERIUM-ENRICHED ETORICOXIB
The present application describes deuterium-enriched etoricoxib, 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 15 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 15 is at least 7%, provided that when R 1 -R 3 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 15 is selected from at least 7%, provided that when R 1 -R 3 are D, then at least one other R is D. The abundance can also be at least 6%, at least 13%, at least 20%, at least 27%, at least 33%, at least 40%, at least 47%, at least 53%, at least 60%, at least 67%, at least 73%, at least 80%, at least 87%, at least 93%, and 100%.
3 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 4 -R 7 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 8 -R 9 is selected from at least 50% and 100%.
5 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 10 -R 15 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, 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 15 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 15 is at least 7%, provided that when R 1 -R 3 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 15 is selected from at least 7%, provided that when R 1 -R 3 are D, then at least one other R is D. The abundance can also be at least 6%, at least 13%, at least 20%, at least 27%, at least 33%, at least 40%, at least 47%, at least 53%, at least 60%, at least 67%, at least 73%, at least 80%, at least 87%, at least 93%, and 100%.
10 . An isolated deuterium-enriched compound of claim 8 , wherein the abundance of deuterium in R 4 -R 7 is selected from at least 25%, at least 50%, at least 75%, and 100%.
11 . An isolated deuterium-enriched compound of claim 8 , wherein the abundance of deuterium in R 8 -R 9 is selected from at least 50% and 100%.
12 . An isolated deuterium-enriched compound of claim 8 , wherein the abundance of deuterium in R 10 -R 15 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, 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 15 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 15 is at least 7%, provided that when R 1 -R 3 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 15 is selected from at least 7%, provided that when R 1 -R 3 are D, then at least one other R is D. The abundance can also be at least 6%, at least 13%, at least 20%, at least 27%, at least 33%, at least 40%, at least 47%, at least 53%, at least 60%, at least 67%, at least 73%, at least 80%, at least 87%, at least 93%, 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 a disease selected from rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, chronic low back pain, acute pain and/or gout 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.