DEUTERIUM-ENRICHED VORICONAZOLE
The present application describes deuterium-enriched voriconazole, 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 14 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 14 is at least 7%.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 14 is selected from at least 7%, at least 14%, at least 21%, at least 29%, at least 36%, at least 43%, at least 50%, at least 57%, at least 64%, at least 71%, at least 79%, at least 86%, at least 93%, and 100%.
3 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 is 100%.
4 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 2 -R 14 is selected from at least 8%, at least 15%, at least 23%, at least 31%, at least 38%, at least 46%, at least 54%, at least 62%, at least 69%, at least 77%, at least 85%, at least 92%, and 100%.
5 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 2 -R 4 is at least 33%, at least 67%, and 100%.
6 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 5 -R 8 is 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 9 -R 10 is at least 50% and 100%.
8 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 13 -R 14 is at least 50% and 100%.
9 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-7 of Table 1.
10 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 8-14 of Table 2.
11 . An isolated deuterium-enriched compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 14 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 14 is at least 7%.
12 . An isolated deuterium-enriched compound of claim 11 , wherein the abundance of deuterium in R 1 -R 14 is selected from at least 7%, at least 14%, at least 21%, at least 29%, at least 36%, at least 43%, at least 50%, at least 57%, at least 64%, at least 71%, at least 79%, at least 86%, at least 93%, and 100%.
13 . An isolated deuterium-enriched compound of claim 11 , wherein the abundance of deuterium in R 1 is 100%.
14 . An isolated deuterium-enriched compound of claim 11 , wherein the compound is selected from compounds 1-7 of Table 1.
15 . An isolated deuterium-enriched compound of claim 11 , wherein the compound is selected from compounds 8-14 of Table 2.
16 . A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 14 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 14 is at least 7%.
17 . A mixture of deuterium-enriched compounds of claim 16 , wherein the compounds are selected from compounds 1-7 of Table 1.
18 . A mixture of deuterium-enriched compounds of claim 16 , wherein the compounds are selected from compounds 8-14 of Table 2.
19 . 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.
20 . A method for treating a disease selected from invasive candidiasis, invasive aspergillosis, and/or emerging fungal infections 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.