DEUTERIUM-ENRICHED ESCITALOPRAM
The present application describes deuterium-enriched escitalopram, 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%, provided that if R 1 -R 3 or R 7 -R 8 are 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 21 is selected from at least 5%, 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%, (k) 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 -R 6 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, and 100%.
4 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 7 -R 12 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, and 100%.
5 . 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 50%, at least 75%, and 100%.
6 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 15 -R 17 is selected from at least 33%, at least 67%, and 100%.
7 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 12 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%.
8 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 13 -R 14 is selected from at least 50%, and b 100 %.
9 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 13 -R 14 is selected from at least 20%, at least 40%, at least 60%, at least 80%, and 100%.
10 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-17 of Table 1 as follows:
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
11 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 18-34 of Table 2 as follows:
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
12 . An isolated 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%, provided that if R 1 -R 3 or R 7 -R 8 are D,
then at least one other R is a D.
13 . An isolated deuterium-enriched compound of claim 12 , wherein the abundance of deuterium in R 1 -R 21 is selected from at least 5%, 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%, (k) 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%.
14 . An isolated deuterium-enriched compound of claim 12 , wherein the abundance of deuterium in R 1 -R 6 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, and 100%.
15 . An isolated deuterium-enriched compound of claim 12 , wherein the abundance of deuterium in R 7 -R 12 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, and 100%.
16 . An isolated deuterium-enriched compound of claim 12 , wherein the abundance of deuterium in R 18 -R 21 is selected from at least 25%, at least 50%, at least 75%, and 100%.
17 . An isolated deuterium-enriched compound of claim 12 , wherein the abundance of deuterium in R 15 -R 17 is selected from at least 33%, at least 67%, and 100%.
18 . An isolated deuterium-enriched compound of claim 12 , wherein the abundance of deuterium in R 1 -R 12 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%.
19 . An isolated deuterium-enriched compound of claim 12 , wherein the abundance of deuterium in R 13 -R 14 is selected from at least 50%, and 100%.
20 . An isolated deuterium-enriched compound of claim 12 , wherein the abundance of deuterium in R 13 -R 17 is selected from at least 20%, at least 40%, at least 60%, at least 80%, and 100%.
21 . An isolated deuterium-enriched compound of claim 12 , wherein the compound is selected from compounds 1-17 of Table 1 as follows:
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
22 . An isolated deuterium-enriched compound of claim 12 , wherein the compound is selected from compounds 18-34 of Table 2 as follows:
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
23 . A mixture of deuterium-enriched compounds 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%, provided that if R 1 -R 3 or R 7 -R 8 are D,
then at least one other R is a D.
24 . A mixture of deuterium-enriched compounds of claim 23 , wherein the abundance of deuterium in R 1 -R 21 is selected from at least 5%, 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%, (k) 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%.
25 . A mixture of deuterium-enriched compounds of claim 23 , wherein the abundance of deuterium in R 1 -R 6 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, and 100%.
26 . A mixture of deuterium-enriched compounds of claim 23 , wherein the abundance of deuterium in R 7 -R 12 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, and 100%.
27 . A mixture of deuterium-enriched compounds of claim 23 , wherein the abundance of deuterium in R 18 -R 21 is selected from at least 25%, at least 50%, at least 75%, and 100%.
28 . A mixture of deuterium-enriched compounds of claim 23 , wherein the abundance of deuterium in R 15 -R 17 is selected from at least 33%, at least 67%, and 100%.
29 . A mixture of deuterium-enriched compounds of claim 23 , wherein the abundance of deuterium in R 1 -R 12 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%.
30 . A mixture of deuterium-enriched compounds of claim 23 , wherein the abundance of deuterium in R 13 -R 14 is selected from at least 50%, and 100%.
31 . A mixture of deuterium-enriched compounds of claim 23 , wherein the abundance of deuterium in R 13 -R 17 is selected from at least 20%, at least 40%, at least 60%, at least 80%, and 100%.
32 . A mixture of deuterium-enriched compound of claim 23 , wherein the compound is selected from compounds 1-17 of Table 1 as follows:
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
33 . A mixture of deuterium-enriched compound of claim 23 , wherein the compound is selected from compounds 18-34 of Table 2 as follows:
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
34 . 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.
35 . A method for treating a disease selected from major depressive disorder, generalized anxiety disorder, social anxiety disorder, panic disorder, and/or obsessive compulsive disorder 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.