DEUTERIUM-ENRICHED SUNITINIB
The present application describes deuterium-enriched sunitinib, 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 27 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 27 is at least 4%.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 27 is selected from at least 4%, at least 7%, at least 11%, at least 15%, at least 19%, at least 22%, at least 26%, at least 30%, at least 33%, at least 37%, (j) at least 41%, at least 44%, at least 48%, at least 52%, at least 56%, at least 59%, at least 63%, at least 67%, at least 70%, at least 74%, at least 78%, at least 81%, at least 85%, at least 89%, at least 93%, at least 96%, and 100%.
3 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 3 is selected from at least 33%, at least 67%, and 100%.
4 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 4 -R 27 is selected from at least 4%, at least 8%, at least 13%, at least 17%, at least 21%, at least 25%, at least 29%, at least 33%, at least 38%, at least 42%, (j) at least 46%, at least 50%, at least 54%, at least 58%, at least 63%, at least 67%, at least 71%, at least 75%, at least 79%, at least 83%, at least 88%, at least 92%, at least 96%, and 100%.
5 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 4 -R 6 is selected from at least 33%, at least 67%, and 100%.
6 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 8 -R 10 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 11 -R 13 is selected from at least 33%, at least 67%, and 100%.
8 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 14 -R 17 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 18 -R 27 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%.
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 27 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 27 is at least 4%.
13 . An isolated deuterium-enriched compound of claim 12 , wherein the abundance of deuterium in R 1 -R 27 is selected from at least 4%, at least 7%, at least 11%, at least 15%, at least 19%, at least 22%, at least 26%, at least 30%, at least 33%, at least 37%, (j) at least 41%, at least 44%, at least 48%, at least 52%, at least 56%, at least 59%, at least 63%, at least 67%, at least 70%, at least 74%, at least 78%, at least 81%, at least 85%, at least 89%, at least 93%, at least 96%, 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 27 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 27 is at least 4%.
17 . A mixture of deuterium-enriched compounds of claim 16 , wherein the compounds are selected from compounds 1-8 of Table 1.
18 . A mixture of deuterium-enriched compounds of claim 16 , wherein the compounds are 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 a disease selected from gastrointestinal stromal tumor and/or renal cell carcinoma 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.