DEUTERIUM-ENRICHED ATAZANAVIR
The present application describes deuterium-enriched atazanavir, 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 52 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 52 is at least 2%.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 52 is selected from at least 2%, at least 4%, at least 10%, at least 15%, at least 21%, at least 27%, at least 33%, at least 38%, at least 44%, at least 50%, at least 56%, at least 62%, at least 67%, at least 73%, at least 79%, at least 85%, at least 90%, at least 96%, and 100%.
3 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 5 is selected from at least 20%, at least 40%, at least 60%, at least 80%, and 100%.
4 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 6 -R 8 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 9 -R 18 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 19 -R 21 and R 27 -R 31 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%.
7 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 22 -R 26 is selected from at least 20%, at least 40%, at least 60%, at least 80%, and 100%.
8 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 32 -R 35 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 36 -R 39 is selected from at least 25%, at least 50%, at least 75%, and 100%.
10 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 40 -R 49 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%.
11 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 50 -R 52 is selected from at least 33%, at least 67%, 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 52 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 52 is at least 2%.
15 . An isolated deuterium-enriched compound of claim 14 , wherein the compound is selected from compounds 1-10 of Table 1.
16 . An isolated deuterium-enriched compound of claim 14 , wherein the compound is selected from compounds 11-20 of Table 2.
17 . A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 52 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 52 is at least 2%.
18 . A mixture of deuterium-enriched compound of claim 27 , wherein the compound is selected from compounds 1-10 of Table 1.
19 . A mixture of deuterium-enriched compound of claim 27 , wherein the compound is selected from compounds 11-20 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 human immunodeficiency virus 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.