DEUTERIUM-ENRICHED TACROLIMUS
The present application describes deuterium-enriched tacrolimus, 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 69 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 69 is at least 1%.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 69 is selected from at least 1%, at least 3%, at least 9%, at least 14%, at least 20%, at least 29%, at least 35%, at least 41%, at least 46%, at least 52%, at least 57%, at least 62%, at least 68%, at least 74%, at least 80%, at least 86%, at least 91%, at least 97%, and 100%.
3 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 3 is selected from at least 33%, at least 67%, and 100%.
4 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 4 -R 12 is selected from at least 11%, at least 22%, at least 33%, at least 44%, at least 56%, at least 67%, at least 78%, 100%.
5 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 18 -R 20 and R 24 -R 29 is selected from at least 11%, at least 22%, at least 33%, at least 44%, at least 56%, at least 67%, at least 78%, 100%.
6 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 21 -R 23 is selected from at least 33%, at least 67%, and 100%.
7 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 56 -R 58 is selected from at least 33%, at least 67%, and 100%.
8 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 61 -R 63 is selected from at least 33%, at least 67%, and 100%.
9 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-8 of Table 1.
10 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 9-16 of Table 2.
11 . An isolated deuterium-enriched compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 69 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 69 is at least 1%.
12 . An isolated deuterium-enriched compound of claim 11 , wherein the abundance of deuterium in R 1 -R 69 is selected from at least 1%, at least 3%, at least 9%, at least 14%, at least 20%, at least 29%, at least 35%, at least 41%, at least 46%, at least 52%, at least 57%, at least 62%, at least 68%, at least 74%, at least 80%, at least 86%, at least 91%, at least 97%, and 100%.
13 . An isolated deuterium-enriched compound of claim 11 , wherein the abundance of deuterium in R 1 -R 3 is selected from at least 33%, at least 67%, and 100%.
14 . An isolated deuterium-enriched compound of claim 11 , wherein the compound is selected from compounds 1-8 of Table 1.
15 . An isolated deuterium-enriched compound of claim 11 , wherein the compound is selected from compounds 9-16 of Table 2.
16 . A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 69 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 69 is at least 1%.
17 . A mixture of deuterium-enriched compound of claim 16 , wherein the compound is selected from compounds 1-8 of Table 1.
18 . A mixture of deuterium-enriched compound of claim 16 , wherein the compound is selected from compounds 9-16 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 severe atopic dermatitis, severe refractory uveitis after bone marrow transplants, and/or vitiligo 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.