DEUTERIUM-ENRICHED OLANZAPINE
The present application describes deuterium-enriched olanzapine, 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 20 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 20 is at least 5%, provided that if R 14 -R 16 are D, then at least one of R is D.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 20 is selected from 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%, (k) 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%.
3 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 is selected from 100%.
4 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 2 -R 5 is selected from at least 25%, at least 50%, at least 75%, and 100%.
5 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 6 -R 13 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 17 is selected from 100%.
7 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 18 -R 20 is selected from at least 33%, at least 67%, and 100%.
8 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-6 of Table 1:
9 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 7-12 of Table 2:
10 . An isolated deuterium-enriched compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 20 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 20 is at least 5%, provided that if R 14 -R 16 are D, then at least one of R is D.
11 . An isolated deuterium-enriched compound of claim 10 , wherein the abundance of deuterium in R 1 -R 20 is selected from 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%, (k) 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%.
12 . An isolated deuterium-enriched compound of claim 10 , wherein the abundance of deuterium in R 1 is selected from 100%.
13 . An isolated deuterium-enriched compound of claim 10 , wherein the abundance of deuterium in R 2 -R 5 is selected from at least 25%, at least 50%, at least 75%, and 100%.
14 . An isolated deuterium-enriched compound of claim 10 , wherein the abundance of deuterium in R 6 -R 13 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%.
15 . An isolated deuterium-enriched compound of claim 10 , wherein the abundance of deuterium in R 17 is selected from 100%.
16 . An isolated deuterium-enriched compound of claim 10 , wherein the abundance of deuterium in R 1 -R 20 is selected from at least 33%, at least 67%, and 100%.
17 . An isolated deuterium-enriched compound of claim 10 , wherein the compound is selected from compounds I-6 of Table 1:
18 . An isolated deuterium-enriched compound of claim 10 , wherein the compound is selected from compounds 7-12 of Table 2:
19 . A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 20 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 20 is at least 5%, provided that if R 14 -R 16 are D, then at least one of R is D.
20 . A mixture of deuterium-enriched compound of claim 19 , wherein the abundance of deuterium in R 1 -R 20 is selected from 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%, (k) 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%.
21 . A mixture of deuterium-enriched compound of claim 19 , wherein the abundance of deuterium in R 1 is selected from 100%.
22 . A mixture of deuterium-enriched compound of claim 19 , wherein the abundance of deuterium in R 2 -R 5 is selected from at least 25%, at least 50%, at least 75%, and 100%.
23 . A mixture of deuterium-enriched compound of claim 19 , wherein the abundance of deuterium in R 6 -R 13 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%.
24 . A mixture of deuterium-enriched compound of claim 19 , wherein the abundance of deuterium in R 17 is selected from 100%.
25 . A mixture of deuterium-enriched compound of claim 19 , wherein the abundance of deuterium in R 18 -R 20 is selected from at least 33%, at least 67%, and 100%.
26 . A mixture of deuterium-enriched compound of claim 19 , wherein the compound is selected from compounds 1-6 of Table 1:
27 . A mixture of deuterium-enriched compound of claim 19 , wherein the compound is selected from compounds 7-12 of Table 2:
28 . 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.
29 . A method for treating a disease selected from schizophrenia, bipolar disorder, and/or psychotic depression, 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.