DEUTERIUM-ENRICHED LAPATINIB
The present application describes deuterium-enriched lapatinib, 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 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 11 is selected from at least 50% and 100%.
7 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 12 -R 13 is selected from at least 50% 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 20 is selected from at least 33%, at least 67%, and 100%.
10 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 21 -R 22 is selected from at least 50% and 100%.
11 . 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%.
12 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-10 of Table 1.
13 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 11-20 of Table 2.
14 . 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%.
15 . An isolated deuterium-enriched compound of claim 14 , wherein the compound is selected from compounds I-10 of Table 1.
16 . An isolated deuterium-enriched compound of claim 14 , wherein the compound is selected from compounds II-20 of Table 2.
17 . 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%.
18 . A mixture of deuterium-enriched compound of claim 17 , wherein the compound is selected from compounds I-10 of Table 1.
19 . A mixture of deuterium-enriched compound of claim 17 , wherein the compound is selected from compounds II-20 of Table 2.
20 . 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.
21 . A method for treating metastatic breast 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.