DEUTERIUM-ENRICHED BUDESONIDE
The present application describes deuterium-enriched budesonide, 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 34 are independently selected from H and D; and the abundance of deuterium in R 1 -R 34 is at least 3%, provided that when (i) R 4 and R 6-7 are D at least one other R is D, (ii) when R 15-22 are D then at least one other R is D, and (iii) when R 16-22 are D then at least one other R besides R 15 is D.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 34 is selected from at least 3%, at least 6%, at least 12%, at least 18%, at least 24%, at least 29%, at least 35%, at least 41%, at least 47%, at least 53%, at least 59%, at least 65%, at least 71%, at least 76%, at least 82%, at least 88%, at least 94%, and 100%.
3 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 2 is selected from at least 50% and 100%.
4 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 4 -R 7 and R 23 -R 24 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, and 100%.
5 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 2 , R 4 -R 7 , and R 23 -R 24 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%.
6 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 15 -R 22 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 27 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, and 100%.
8 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 32 -R 34 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- 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 34 are independently selected from H and D; and the abundance of deuterium in R 1 -R 34 is at least 3%, provided that when (i) R 4 and R 6-7 are D at least one other R is D, (ii) when R 15-22 are D then at least one other R is D, and (iii) when R 16-22 are D then at least one other R besides R 15 is D.
12 . An isolated deuterium-enriched compound of claim 11 , wherein the abundance of deuterium in R 1 -R 34 is selected from at least 3%, at least 6%, at least 12%, at least 18%, at least 24%, at least 29%, at least 35%, at least 41%, at least 47%, at least 53%, at least 59%, at least 65%, at least 71%, at least 76%, at least 82%, at least 88%, at least 94%, and 100%.
13 . An isolated deuterium-enriched compound of claim 11 , wherein the abundance of deuterium in R 1 -R 2 is selected from at least 50% and 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 34 are independently selected from H and D; and the abundance of deuterium in R 1 -R 34 is at least 3%, provided that when (i) R4 and R 6-7 are D at least one other R is D, (ii) when R 15-22 are D then at least one other R is D, and (iii) when R 16-22 are D then at least one other R besides R 15 is D.
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 asthma, non-infectious rhinitis, and nasal polyposis 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.