DEUTERIUM-ENRICHED LETROZOLE
The present application describes deuterium-enriched letrozole, 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 11 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 11 is at least 9%.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 11 is selected from at least 9%, at least 18%, at least 27%, at least 36%, at least 45%, at least 56%, at least 64%, at least 73%, at least 82%, at least 91%, 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 is selected from at least 100%.
5 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 4 -R 7 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 8 -R 11 is selected from at least 25%, at least 50%, at least 75%, and 100%.
7 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-5 of Table 1.
8 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 6-10 of Table 2.
9 . An isolated deuterium-enriched compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 11 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 11 is at least 9%.
10 . An isolated deuterium-enriched compound of claim 9 , wherein the abundance of deuterium in R 1 -R 11 is selected from at least 9%, at least 18%, at least 27%, at least 36%, at least 45%, at least 56%, at least 64%, at least 73%, at least 82%, at least 91%, and 100%.
11 . An isolated deuterium-enriched compound of claim 9 , wherein the abundance of deuterium in R 1 -R 2 is selected from at least 50% and 100%.
12 . An isolated deuterium-enriched compound of claim 9 , wherein the abundance of deuterium in R 3 is selected from at least 100%.
13 . An isolated deuterium-enriched compound of claim 9 , wherein the abundance of deuterium in R 4 -R 7 is selected from at least 25%, at least 50%, at least 75%, and 100%.
14 . An isolated deuterium-enriched compound of claim 9 , wherein the abundance of deuterium in R 8 -R 11 is selected from at least 25%, at least 50%, at least 75%, and 100%.
15 . An isolated deuterium-enriched compound of claim 9 , wherein the compound is selected from compounds 1-5 of Table 1.
16 . An isolated deuterium-enriched compound of claim 9 , wherein the compound is selected from compounds 6-10 of Table 2.
17 . A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 11 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 11 is at least 9%.
18 . A mixture of deuterium-enriched compound of claim 17 , wherein the compound is selected from compounds 1-5 of Table 1.
19 . A mixture of deuterium-enriched compound of claim 17 , wherein the compound is selected from compounds 6-10 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 hormonally-responsive 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.