DEUTERIUM-ENRICHED IMATINIB
The present application describes deuterium-enriched imatinib, 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 31 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 31 is at least 3%.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 31 is selected from at least 3%, at least 6%, at least 13%, at least 19%, at least 26%, at least 32%, at least 39%, at least 45%, at least 52%, at least 58%, at least 65%, at least 71%, at least 77%, at least 84%, at least 90%, at least 97%, 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 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 7 -R 8 is selected from at least 50% and 100%.
6 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 9 -R 14 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, and 100%.
7 . 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%.
8 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 19 -R 20 is selected from at least 50% and 100%.
9 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 21 -R 28 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%.
10 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 29 -R 31 is selected from at least 33%, at least 67%, and 100%.
11 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-9 of Table 1.
12 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 10-18 of Table 2.
13 . An isolated deuterium-enriched compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 31 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 31 is at least 3%.
14 . An isolated deuterium-enriched compound of claim 12 , wherein the compound is selected from compounds 1-9 of Table 1.
15 . An isolated deuterium-enriched compound of claim 12 , wherein the compound is selected from compounds 10-18 of Table 2.
16 . A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 31 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 31 is at least 3%.
17 . A mixture of deuterium-enriched compound of claim 16 , wherein the compound is selected from compounds 1-9 of Table 1.
18 . A mixture of deuterium-enriched compound of claim 16 , wherein the compound is selected from compounds 10-18 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 chronic myelogenous leukemia and/or gastrointestinal stromal tumors 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.