DEUTERIUM-ENRICHED AROXIFENE
The present application describes deuterium-enriched arzoxifene, 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 29 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 29 is at least 3%.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 29 is selected from at least 3%, at least 7%, at least 14%, at least 21%, at least 28%, at least 34%, at least 41%, at least 48%, at least 55%, at least 62%, at least 69%, at least 76%, at least 83%, at least 90%, at least 97%, and 100%.
3 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 is selected from 100%.
4 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 2 and R 29 is selected from at least 50% and 100%.
5 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 2 , R 4 -R 7 , and R 25 -R 29 is selected from at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, and 100%.
6 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 2 -R 7 , and R 25 -R 29 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%.
7 . 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%.
8 . 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%.
9 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 12 -R 21 is selected from at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, and 100%.
10 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 22 -R 24 is selected from at least 33%, at least 67%, and 100%.
11 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 25 -R 28 is selected from at least 25%, at least 50%, at least 75%, and 100%.
12 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 2 -R 3 and R 29 is selected from at least 33%, at least 67%, and 100%.
13 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-11 of Table 1.
14 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 12-22 of Table 2.
15 . An isolated deuterium-enriched compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 29 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 29 is at least 3%.
16 . An isolated deuterium-enriched compound of claim 15 , wherein the compound is selected from compounds 1-11 of Table 1.
17 . An isolated deuterium-enriched compound of claim 15 , wherein the compound is selected from compounds 12-22 of Table 2.
18 . A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 29 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 29 is at least 3%.
19 . A mixture of deuterium-enriched compound of claim 18 , wherein the compound is selected from compounds 1-11 of Table 1.
20 . A mixture of deuterium-enriched compound of claim 18 , wherein the compound is selected from compounds 12-22 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 a disease selected from osteoporosis, breast cancer prevention, and/or endometrial 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.