DEUTERIUM-ENRICHED TAMSULOSIN
The present application describes deuterium-enriched tamsulosin, 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 28 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 28 is at least 4%, provided that if R 16 or R 17 is 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 28 is selected from at least 4%, at least 8%, at least 12%, at least 16%, at least 20%, at least 24%, at least 28%, at least 32%, at least 36%, at least 40%, at least 44%, at least 48%, at least 52%, at least 56%, at least 60%, at least 64%, at least 68%, at least 72%, at least 76%, at least 80%, at least 84%, at least 88%, at least 92%, at least 96%, 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 6 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 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 19 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%.
7 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 20 -R 23 is selected from at least 25%, at least 50%, at least 75%, and 100%.
8 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 24 -R 28 is selected from at least 20%, at least 40%, at least 60%, at least 80%, 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 28 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 28 is at least 4%, provided that if R 16 or R 17 is D, then at least one other R is a D.
12 . An isolated deuterium-enriched compound of claim 11 , wherein the abundance of deuterium in R 1 -R 28 is selected from at least 4%, at least 8%, at least 12%, at least 16%, at least 20%, at least 24%, at least 28%, at least 32%, at least 36%, at least 40%, at least 44%, at least 48%, at least 52%, at least 56%, at least 60%, at least 64%, at least 68%, at least 72%, at least 76%, at least 80%, at least 84%, at least 88%, at least 92%, at least 96%, 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 abundance of deuterium in R 4 -R 6 is selected from at least 33%, at least 67%, and 100%.
15 . An isolated deuterium-enriched compound of claim 11 , wherein the abundance of deuterium in R 7 -R 9 is selected from at least 33%, at least 67%, and 100%.
16 . An isolated deuterium-enriched compound of claim 11 , wherein the abundance of deuterium in R 10 -R 19 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%.
17 . An isolated deuterium-enriched compound of claim 11 , wherein the abundance of deuterium in R 20 -R 23 is selected from at least 25%, at least 50%, at least 75%, and 100%.
18 . An isolated deuterium-enriched compound of claim 11 , wherein the abundance of deuterium in R 24 -R 28 is selected from at least 20%, at least 40%, at least 60%, at least 80%, and 100%.
19 . An isolated deuterium-enriched compound of claim 11 , wherein the compound is selected from compounds 1-7 of Table 1:
20 . An isolated deuterium-enriched compound of claim 11 , wherein the compound is selected from compounds 8-14 of Table 2:
21 . A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 28 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 28 is at least 4%, provided that if R 16 or R 17 is D, then at least one other R is a D.
22 . A mixture of deuterium-enriched compound of claim 21 , wherein the abundance of deuterium in R 1 -R 28 is selected from at least 4%, at least 8%, at least 12%, at least 16%, at least 20%, at least 24%, at least 28%, at least 32%, at least 36%, at least 40%, at least 44%, at least 48%, at least 52%, at least 56%, at least 60%, at least 64%, at least 68%, at least 72%, at least 76%, at least 80%, at least 84%, at least 88%, at least 92%, at least 96%, and 100%.
23 . A mixture of deuterium-enriched compound of claim 21 , wherein the abundance of deuterium in R 1 -R 3 is selected from at least 33%, at least 67%, and 100%.
24 . A mixture of deuterium-enriched compound of claim 21 , wherein the abundance of deuterium in R 4 -R 6 is selected from at least 33%, at least 67%, and 100%.
25 . A mixture of deuterium-enriched compound of claim 21 , wherein the abundance of deuterium in R 7 -R 9 is selected from at least 33%, at least 67%, and 100%.
26 . A mixture of deuterium-enriched compound of claim 21 , wherein the abundance of deuterium in R 10 -R 19 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%.
27 . A mixture of deuterium-enriched compound of claim 21 , wherein the abundance of deuterium in R 20 -R 23 is selected from at least 25%, at least 50%, at least 75%, and 100%.
28 . A mixture of deuterium-enriched compound of claim 21 , wherein the abundance of deuterium in R 24 -R 28 is selected from at least 20%, at least 40%, at least 60%, at least 80%, and 100%.
29 . A mixture of deuterium-enriched compound of claim 21 , wherein the compound is selected from compounds 1-7 of Table 1:
30 . A mixture of deuterium-enriched compound of claim 21 , wherein the compound is selected from compounds 8-14 of Table 2:
31 . 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.
32 . A method for treating benign prostatic hyperplasia 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.