DEUTERIUM-ENRICHED DASATINIB
The present application describes deuterium-enriched dasatinib, 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 26 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 26 is at least 4%.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 26 is selected from at least 4%, at least 8%, at least 12%, at least 15%, at least 19%, at least 23%, at least 27%, at least 31%, at least 35%, at least 38%, at least 42%, at least 46%, at least 50%, at least 54%, at least 58, at least 62%, at least 65%, at least 69%, at least 73%, at least 77%, at least 81%, at least 85%, at least 88%, at least 92%, 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 6 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 7 -R 9 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 10 is 100%.
7 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 11 is 100%.
8 . 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%.
9 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 15 -R 22 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 23 -R 26 is selected from at least 25%, at least 50%, at least 75%, 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 26 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 26 is at least 4%.
14 . An isolated deuterium-enriched compound of claim 13 , wherein the compound is selected from compounds 1-9 of Table 1.
15 . An isolated deuterium-enriched compound of claim 13 , 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 26 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 26 is at least 4%.
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 chronic myelogenous leukemia 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.