DEUTERIUM-ENRICHED BIFEPRUNOX
The present application describes deuterium-enriched bifeprunox, 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 23 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 23 is at least 4%.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 23 is selected from at least 4%, at least 9%, at least 13%, at least 17%, at least 22%, at least 26%, at least 30%, at least 35%, at least 39%, at least 43%, at least 48%, at least 52%, at least 57%, at least 61%, at least 65%, at least 70%, at least 74%, at least 78%, at least 83%, at least 87%, at least 91%, at least 96%, 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 4 and R 15 -R 23 is selected from at least 8%, at least 17%, at least 25%, at least 33%, at least 42%, at least 50%, at least 58%, at least 67%, at least 75%, at least 83%, at least 92%, and 100%.
5 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 5 -Ris 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%.
6 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 4 and R 15 -R 23 is selected from at least 8%, at least 15%, at least 23%, at least 31%, at least 38%, at least 46%, at least 54%, at least 62%, at least 69%, at least 77%, at least 85%, at least 92%, and 100%.
7 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 and R 5 -R 14 is selected from at least 9%, at least 18%, at least 27%, at least 36%, at least 45%, at least 56%, at least 64%, at least 73%, at least 82%, at least 91%, and 100%.
8 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 2 -R 23 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%.
9 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 5 -R 12 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%.
10 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 13 -R 14 is selected from at least 50% and 100%.
11 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 15 -R 18 is selected from at least 25%, at least 50%, at least 75%, and 100%.
12 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 19 -R 23 is selected from at least 20%, at least 40%, at least 60%, at least 80%, and 100 %.
13 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-11 of Table 1 as follows:
1
2
3
4
5
6
7
8
9
10
11
14 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 12-22 of Table 2 as follows:
12
13
14
15
16
17
18
19
20
21
22
15 . An isolated deuterium-enriched compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 23 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 23 is at least 40%.
16 . An isolated deuterium-enriched compound of claim 15 , wherein the abundance of deuterium in R 1 -R 23 is selected from at least 4%, at least 9%, at least 13%, at least 17%, at least 22%, at least 26%, at least 30%, at least 35%, at least 39%, at least 43%, at least 48%, at least 52%, at least 57%, at least 61%, at least 65%, at least 70%, at least 74%, at least 78%, at least 83%, at least 87%, at least 91%, at least 96%, and 100%.
17 . An isolated deuterium-enriched compound of claim 15 , wherein the abundance of deuterium in R 1 is selected from 100%.
18 . An isolated deuterium-enriched compound of claim 15 , wherein the abundance of deuterium in R 2 -R 4 and R 15 -R 23 is selected from at least 80%, at least 17%, at least 25%, at least 33%, at least 42%, at least 50%, at least 58%, at least 67%, at least 75%, at least 83%, at least 92%, and 100%.
19 . An isolated deuterium-enriched compound of claim 15 , wherein the abundance of deuterium in R 5 -R 14 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%.
20 . An isolated deuterium-enriched compound of claim 15 , wherein the abundance of deuterium in R 1 -R 4 and R 15 -R 23 is selected from at least 8%, at least 15%, at least 23%, at least 31%, at least 38%, at least 46%, at least 54%, at least 62%, at least 69%, at least 77%, at least 85%, at least 92%, and 100%.
21 . An isolated deuterium-enriched compound of claim 15 , wherein the abundance of deuterium in R 1 and R 5 -R 14 is selected from at least 9%, at least 18%, at least 27%, at least 36%, at least 45%, at least 56%, at least 64%, at least 73%, at least 82%, at least 91%, and 100%.
22 . An isolated deuterium-enriched compound of claim 15 , wherein the abundance of deuterium in R 2 -R 23 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%.
23 . An isolated deuterium-enriched compound of claim 15 , wherein the abundance of deuterium in R 5 -R 12 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 . An isolated deuterium-enriched compound of claim 15 , wherein the abundance of deuterium in R 13 -R 14 selected from at least 50 and 100%.
25 . An isolated deuterium-enriched compound of claim 15 , wherein the abundance of deuterium in R 15 -R 18 is selected from at least 25%, at least 50%, at least 75%, and 100%.
26 . An isolated deuterium-enriched compound of claim 15 , wherein the abundance of deuterium in R 19 -R 23 is selected from at least 20%, at least 40%, at least 60%, at least 80%, and 100%.
27 . An isolated deuterium-enriched compound of claim 15 , wherein the compound is selected from compounds 1-11 of Table 1 as follows:
1
2
3
4
5
6
7
8
9
10
11
28 . An isolated deuterium-enriched compound of claim 15 , wherein the compound is selected from compounds 12-22 of Table 2 as follows:
12
13
14
15
16
17
18
19
20
21
22
29 . A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 23 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 23 is at least 4%.
30 . A mixture of deuterium-enriched compound of claim 29 , wherein the abundance of deuterium in R 1 -R 23 is selected from at least 4%, at least 9%, at least 13%, at least 17%, at least 22%, at least 26%, at least 30%, at least 35%, at least 39%, at least 43%, at least 48%, at least 52, at least 57%, at least 61%, at least 65%, at least 70%, at least 74%, at least 78%, at least 83%, at least 87%, at least 91%, at least 96%, and 100%.
31 . A mixture of deuterium-enriched compound of claim 29 , wherein the abundance of deuterium in R 1 is selected from 100%.
32 . A mixture of deuterium-enriched compound of claim 29 , wherein the abundance of deuterium in R 2 -R 4 and R 15 -R 23 is selected from at least 8%, at least 17%, at least 25%, at least 33%, at least 42%, at least 50%, at least 58%, at least 67%, at least 75%, at least 83%, at least 92%, and 100%.
33 . A mixture of deuterium-enriched compound of claim 29 , wherein the abundance of deuterium in R 5 -R 14 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%.
34 . A mixture of deuterium-enriched compound of claim 29 , wherein the abundance of deuterium in R 1 -R 4 and R 15 -R 23 is selected from at least 8%, at least 15%, at least 23%, at least 31%, at least 38%, at least 46%, at least 54%, at least 62%, at least 69%, at least 77%, at least 85%, at least 92%, and 100%.
35 . A mixture of deuterium-enriched compound of claim 29 , wherein the abundance of deuterium in R 1 and R 5 -R 14 is selected from at least 90%, at least 18%, at least 27%, at least 36%, at least 45%, at least 56%, at least 64%, at least 730, at least 82%, at least 91%, and 100%.
36 . A mixture of deuterium-enriched compound of claim 29 , wherein the abundance of deuterium in R 2 -R 23 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%.
37 . A mixture of deuterium-enriched compound of claim 29 , wherein the abundance of deuterium in R 5 -R 12 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%.
38 . A mixture of deuterium-enriched compound of claim 29 , wherein the abundance of deuterium in R 13 -R 14 is selected from at least 50% and 100%.
39 . A mixture of deuterium-enriched compound of claim 29 , wherein the abundance of deuterium in R 15 -R 18 is selected from at least 25%, at least 50%, at least 75%, and 100%.
40 . A mixture of deuterium-enriched compound of claim 29 , wherein the abundance of deuterium in R 19 -R 23 is selected from at least 20%, at least 40%, at least 60%, at least 80%, and 100%.
41 . A mixture of deuterium-enriched compound of claim 29 , wherein the compound is selected from compounds 1-11 of Table 1 as follows:
1
2
3
4
5
6
7
8
9
10
11
42 . A mixture of deuterium-enriched compound of claim 29 , wherein the compound is selected from compounds 12-22 of Table 2 as follows:
12
13
14
15
16
17
18
19
20
21
22
43 . 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.
44 . 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.