DEUTERIUM-ENRICHED CELECOXIB
The present application describes deuterium-enriched celecoxib, 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 14 are independently selected from H and D; and the abundance of deuterium in R 1 -R 14 is at least 7%.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 14 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%.
3 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 2 is selected from at least 50%, at least 100%.
4 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 3 -R 6 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 8 -R 11 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 12 -R 14 is selected from at least 33%, at least 67%, and 100%.
7 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 2 and R 3 -R 6 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, and 100%.
8 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 2 and R 8 -R 11 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, and 100%.
9 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 2 and R 12 -R 14 is selected from at least 20%, at least 40%, at least 60%, at least 80%, and 100%.
10 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 3 -R 6 and R 8 -R 11 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%.
11 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 3 -R 6 and R 12 -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%.
12 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 8 -R 11 and R 12 -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%.
13 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 2 , R 3 -R 6 , and R 8 -R 11 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%.
14 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 2 , R 3 -R 6 , and R 12 -R 14 is selected from at least 11%, at least 22%, at least 33%, at least 44%, at least 56%, at least 67%, at least 78%, at least 89%, and 100%.
15 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 2 , R 8 -R 11 , and R 12 -R 14 is selected from at least 11%, at least 22%, at least 33%, at least 44%, at least 56%, at least 67%, at least 78%, at least 89%, and 100%.
16 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 3 -R 6 , R 8 -R 11 , and R 12 -R 14 is selected from at least 9%, at least 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%.
17 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-15 of Table 1.
18 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 16-30 of Table 2.
19 . An isolated deuterium-enriched compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 14 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 14 is at least 7%.
20 . An isolated deuterium-enriched compound of claim 19 , wherein the compound is selected from compounds 1-15 of Table 1.
21 . An isolated deuterium-enriched compound of claim 19 , wherein the compound is selected from compounds 16-30 of Table 2.
22 . A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 14 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 14 is at least 7%.
23 . A mixture of deuterium-enriched compounds of claim 22 , wherein the compounds are selected from compounds 1-15 of Table 1.
24 . A mixture of deuterium-enriched compounds of claim 22 , wherein the compounds are selected from compounds 16-30 of Table 2.
25 . 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.
26 . A method for treating pain, tenderness, swelling and stiffniess caused by osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis 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.