DEUTERIUM-ENRICHED DOXAZOSIN
The present application describes deuterium-enriched doxazosin, 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 25 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 25 is at least 4%.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 25 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 2 is selected from at least 50% and 100%.
4 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 3 -R 25 is selected from at least 5%, at least 9%, at least 14%, at least 18%, at least 23%, at least 27%, at least 32%, at least 36%, at least 41%, at least 45%, at least 50%, at least 55%, at least 59%, at least 64%, at least 68%, at least 73%, at least 77%, at least 82%, at least 86%, at least 91%, at least 95%, and 100%.
5 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 3 -R 4 is selected from at least 50%, at least (a) at least 100%.
6 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 5 -R 10 is selected from at least 17%, at least (a) at least 33%, (b) at least 50%, (c) at least 67%, (d) at least 83%, and (e) 100%.
7 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 11 -R 18 is selected from at least 13%, at least (a) at least 25%, (b) at least 38%, (c) at least 50%, (d) at least 63%, (e) at least 75%, (f) at least 88%, and (g) 100%.
8 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 19 -R 21 is selected from at least 33%, at least (a) at least 67%, and (b) 100%.
9 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 22 -R 25 is selected from at least 25%, at least (a) at least 50%, (b) at least 75%, and (c) 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 25 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 25 is at least 4%.
13 . An isolated deuterium-enriched compound of claim 12 , wherein the abundance of deuterium in R 1 -R 25 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%.
14 . An isolated deuterium-enriched compound of claim 12 , wherein the compound is selected from compounds 1-8 of Table 1.
15 . An isolated deuterium-enriched compound of claim 12 , 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 25 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 25 is at least 4%.
17 . A mixture of deuterium-enriched compounds of claim 16 , wherein the compounds are selected from compounds 1-8 of Table 1.
18 . A mixture of deuterium-enriched compounds of claim 16 , wherein the compounds are 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 high blood pressure and/or 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.