DEUTERIUM-ENRICHED FULVESTRANT
The present application describes deuterium-enriched fulvestrant, 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 47 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 47 is at least 2%.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 47 is selected from at least 2%, at least 4%, at least 11%, at least 17%, at least 23%, at least 30%, at least 36%, at least 43%, at least 49%, at least 55%, at least 62%, at least 68%, at least 74%, at least 81%, at least 87%, at least 94%, 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 4 is selected from at least 50% and 100%.
5 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 40 -R 43 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 1 -R 4 is selected from at least 25%, at least 50%, at least 75%, and 100%.
7 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 3 -R 4 and R 40 -R 43 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, and 100%.
8 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 4 and R 40 -R 43 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, and 100%.
9 . 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%.
10 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 6 -R 23 is selected from at least 6%, at least 11%, at least 17%, at least 22%, at least 28%, at least 33%, at least 39%, at least 44%, at least 50%, at least 56%, at least 61%, at least 67%, at least 72%, at least 78%, at least 83%, at least 89%, at least 94%, and 100%.
11 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 24 -R 41 is selected from at least 6%, at least 11%, at least 17%, at least 22%, at least 28%, at least 33%, at least 39%, at least 44%, at least 50%, at least 56%, at least 61%, at least 67%, at least 72%, at least 78%, at least 83%, at least 89%, at least 94%, and 100%.
12 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 42 -R 47 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, and 100%.
13 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-12 of Table 1.
14 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 13-24 of Table 2.
15 . An isolated deuterium-enriched compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 47 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 47 is at least 2%.
16 . An isolated deuterium-enriched compound of claim 15 , wherein the compound is selected from compounds 1-12 of Table 1.
17 . An isolated deuterium-enriched compound of claim 15 , wherein the compound is selected from compounds 13-24 of Table 2.
18 . A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 47 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 47 is at least 2%.
19 . A mixture of deuterium-enriched compound of claim 18 , wherein the compound is selected from compounds 1-12 of Table 1.
20 . A mixture of deuterium-enriched compound of claim 18 , wherein the compound is selected from compounds 13-24 of Table 2.
21 . 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.
22 . A method for treating hormone receptor positive 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.