DEUTERIUM-ENRICHED SALMETEROL
The present application describes deuterium-enriched salmeterol, 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 37 are independently selected from H and D; and the abundance of deuterium in R 1 -R 37 is at least 3%, provided that if R 5 -R 6 and Rio are D, then at least one other R is a D.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 37 is selected from at least 3%, at least 5%, at least 11%, at least 16%, at least 22%, at least 27%, at least 32%, at least 38%, at least 43%, at least 49%, at least 54%, at least 59%, at least 65%, at least 70%, at least 76%, at least 81%, at least 86%, at least 92%, at least 97%, and 100%.
3 . 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%.
4 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 5 -R 6 is selected from at least 50% and 100%.
5 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 7 -R 9 is selected from at least 33%, at least 67%, and 100%.
6 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 10 -R 12 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 13 -R 24 is selected from at least 8%, at least 17%, at least 25%, at least 33%, at least 42%, at least 50%, at least 58%, at least 67%, at least 75%, at least 83%, at least 92%, and 100%.
8 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 25 -R 32 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%.
9 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 33 -R 37 is selected from at least 20%, at least 40%, at least 60%, at least 80%, and 100%.
10 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-8 of Table 1:
11 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 9-16 of Table 2:
12 . An isolated deuterium-enriched compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 37 are independently selected from H and D; and the abundance of deuterium in R 1 -R 37 is at least 3%, provided that if R 5 -R 6 and R 10 are D, then at least one other R is a D.
13 . An isolated deuterium-enriched compound of claim 12 , wherein the abundance of deuterium in R 1 -R 37 is selected from at least 3%, at least 5%, at least 11%, at least 16%, at least 22%, at least 27%, at least 32%, at least 38%, at least 43%, at least 49%, at least 54%, at least 59%, at least 65%, at least 70%, at least 76%, at least 81%, at least 86%, at least 92%, at least 97%, and 100%.
14 . An isolated deuterium-enriched compound of claim 12 , wherein the abundance of deuterium in R 1 -R 4 is selected from at least 25%, at least 50%, at least 75%, and 100%.
15 . An isolated deuterium-enriched compound of claim 12 , wherein the abundance of deuterium in R 5 -R 6 is selected from at least 50% and 100%.
16 . An isolated deuterium-enriched compound of claim 12 , wherein the abundance of deuterium in R 7 -R 9 is selected from at least 33%, at least 67%, and 100%.
17 . An isolated deuterium-enriched compound of claim 12 , wherein the abundance of deuterium in R 10 -R 12 is selected from at least 33%, at least 67%, and 100%.
18 . An isolated deuterium-enriched compound of claim 12 , wherein the abundance of deuterium in R 13 -R 24 is selected from at least 8%, at least 17%, at least 25%, at least 33%, at least 42%, at least 50%, at least 58%, at least 67%, at least 75%, at least 83%, at least 92%, and 100%.
19 . An isolated deuterium-enriched compound of claim 12 , wherein the abundance of deuterium in R 25 -R 32 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%.
20 . An isolated deuterium-enriched compound of claim 12 , wherein the abundance of deuterium in R 33 -R 37 is selected from at least 20%, at least 40%, at least 60%, at least 80%, and 100%.
21 . An isolated deuterium-enriched compound of claim 12 , wherein the compound is selected from compounds 1-8 of Table 1:
22 . An isolated deuterium-enriched compound of claim 12 , wherein the compound is selected from compounds 9-16 of Table 2:
23 . A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 37 are independently selected from H and D; and the abundance of deuterium in R 1 -R 37 is at least 3%, provided that if R 5 -R 6 and R 10 are D, then at least one other R is a D.
24 . A mixture of deuterium-enriched compounds of claim 23 , wherein the abundance of deuterium in R 1 -R 37 is selected from at least 3%, at least 5%, at least 11%, at least 16%, at least 22%, at least 27%, at least 32%, at least 38%, at least 43%, at least 49%, at least 54%, at least 59%, at least 65%, at least 70%, at least 76%, at least 81%, at least 86%, at least 92%, at least 97%, and 100%.
25 . A mixture of deuterium-enriched compounds of claim 23 , wherein the abundance of deuterium in R 1 -R 4 is selected from at least 25%, at least 50%, at least 75%, and 100%.
26 . A mixture of deuterium-enriched compounds of claim 23 , wherein the abundance of deuterium in R 5 -R 6 is selected from at least 50% and 100%.
27 . A mixture of deuterium-enriched compounds of claim 23 , wherein the abundance of deuterium in R 7 -R 9 is selected from at least 33%, at least 67%, and 100%.
28 . A mixture of deuterium-enriched compounds of claim 23 , wherein the abundance of deuterium in R 10 -R 12 is selected from at least 33%, at least 67%, and 100%.
29 . A mixture of deuterium-enriched compounds of claim 23 , wherein the abundance of deuterium in R 13 -R 24 is selected from at least 8%, at least 17%, at least 25%, at least 33%, at least 42%, at least 50%, at least 58%, at least 67%, at least 75%, at least 83%, at least 92%, and 100%.
30 . A mixture of deuterium-enriched compounds of claim 23 , wherein the abundance of deuterium in R 25 -R 32 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%.
31 . A mixture of deuterium-enriched compounds of claim 23 , wherein the abundance of deuterium in R 33 -R 37 is selected from at least 20%, at least 40%, at least 60%, at least 80%, and 100%.
32 . A mixture of deuterium-enriched compounds of claim 23 , wherein the compound is selected from compounds 1-8 of Table 1:
33 . A mixture of deuterium-enriched compounds of claim 23 , wherein the compound is selected from compounds 9-16 of Table 2:
34 . 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.
35 . A method for treating asthma 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.