DEUTERIUM-ENRICHED AXITINIB
The present application describes deuterium-enriched axitinib, 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 18 are independently selected from H and D; and the abundance of deuterium in R 1 -R 18 is at least 6%.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 18 is selected from at least 6% , at least 11%, at least 17%, at least 22%, at least 28%, at least 33%, at least 39%, at least 44%, at least 50%, at least 56%, at least 61%, at least 67%, at least 72%, at least 78%, at least 83%, at least 89%, at least 94%, 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% and 100%.
4 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 3 -R 5 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 6 -R 9 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 10 -R 12 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 13 -R 14 is selected from at least 50% and 100%.
8 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 15 -R 18 is selected from at least 25%, at least 50%, at least 75%, and 100%.
9 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-7 of Table 1.
10 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 8-14 of Table 2.
11 . An isolated deuterium-enriched compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 18 are independently selected from H and D; and the abundance of deuterium in R 1 -R 18 is at least 6%.
12 . An isolated deuterium-enriched compound of claim 11 , wherein the abundance of deuterium in R 1 -R 18 is selected from at least 6% , at least 11%, at least 17%, at least 22%, at least 28%, at least 33%, at least 39%, at least 44%, at least 50%, at least 56%, at least 61%, at least 67%, at least 72%, at least 78%, at least 83%, at least 89%, at least 94%, and 100%.
13 . An isolated deuterium-enriched compound of claim 11 , wherein the abundance of deuterium in R 1 -R 2 is selected from at least 50% and 100%.
14 . An isolated deuterium-enriched compound of claim 11 , wherein the compound is selected from compounds 1-7 of Table 1.
15 . An isolated deuterium-enriched compound of claim 11 , wherein the compound is selected from compounds 8-14 of Table 2.
16 . A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 18 are independently selected from H and D; and the abundance of deuterium in R 1 -R 18 is at least 6%.
17 . A mixture of deuterium-enriched compound of claim 16 , wherein the compound is selected from compounds 1-7 of Table 1.
18 . A mixture of deuterium-enriched compound of claim 16 , wherein the compound is selected from compounds 8-14 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 pancreatic cancer, breast cancer, and/or colorectal cancer 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.