DEUTERIUM-ENRICHED ZIPRASIDONE
The present application describes deuterium-enriched ziprasidone, 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 21 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 21 is at least 5%.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 21 is at least 5%, at least at least 10%, at least 14%, at least 19%, at least 24%, at least 29%, at least 33%, at least 38%, at least 43%, at least 48%, at least 52%, at least 57%, at least 62%, at least 67%, at least 71%, at least 76%, at least 81%, at least 86%, at least 90%, at least 95%, and 100%.
3 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 is 100%.
4 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 2 -R 3 is at least 50% or 100%.
5 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 4 -R 21 is at least 6% , at least 11%, at least 17%, at least 22%, at least 28%, at least 33%, at least 39%, at least 44%, at least 50%, at least 56%, at least 61%, at least 67%, at least 72%, at least 78%, at least 83%, at least 89%, at least 94%, and 100%.
6 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 and R 2 -R 3 is at least 33%, at least 67%, and 100%.
7 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 and R 4 -R 21 is at least 5% , at least 11%, at least 16%, at least 21%, at least 26%, at least 32%, at least 37%, at least 42%, at least 47%, at least 53%, at least 58%, at least 63%, at least 68%, at least 74%, at least 79%, at least 84%, at least 89%, at least 95%, and 100%.
8 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 2 -R 3 and R 4 -R 21 is at least 5% , at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, and 100%.
9 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 4 -R 5 is selected from at least 50%, at least (a) at least 100%.
10 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 6 -R 9 is selected from at least 25%, at least (a) at least 50%, (b) at least 75%, and (c) 100%.
11 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 10 -R 17 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%.
12 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 18 -R 21 is selected from at least 25%, at least (a) at least 50%, (b) at least 75%, and (c) 100%.
13 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-11 of Table 1.
14 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 12-22 of Table 2.
15 . 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%.
16 . An isolated deuterium-enriched compound of claim 15 , wherein the compound is selected from compounds 1-11 of Table 1.
17 . An isolated deuterium-enriched compound of claim 15 , wherein the compound is selected from compounds 12-22 of Table 2.
18 . 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%.
19 . A mixture of deuterium-enriched compounds of claim 18 , wherein the compounds are selected from compounds 1-11 of Table 1.
20 . A mixture of deuterium-enriched compounds of claim 18 , wherein the compounds are selected from compounds 12-22 of Table 2.
21 . 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.
22 . A method for treating schizophrenia 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.