DEUTERIUM-ENRICHED MONTELUKAST
The present application describes deuterium-enriched montelukast, 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 36 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 36 is at least 3%.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 36 is selected from (a) at least 6%, (b) at least 11%, (c) at least 17%, (d) at least 22%, (e) at least 28%, (f) at least 33%, (g) at least 39%, (h) at least 44%, (i) at least 50%, (j) at least 50%, (k) at least 50%, (l) at least 50%, (m) at least 56%, (n) at least 61%, (o) at least 67%, (p) at least 72%, (q) at least 78%, (r) at least 83%, (s) at least 89%, (t) at least 94%, and (r) 100%.
3 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 2 is selected from at least 35%, at least 67%, and 100%.
4 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 3 -R 4 is selected from at least 50% and 100%.
5 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 5 -R 8 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 9 -R 10 is selected from at least 50% and 100%.
7 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 12 -R 15 is selected from at least 25%, at least 50%, at least 75%, and 100%.
8 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 16 -R 19 is selected from at least 25%, at least 50%, at least 75%, and 100%.
9 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 20 -R 25 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, and 100%.
10 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 26 -R 29 is selected from at least 25%, at least 50%, at least 75%, and 100%.
11 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 30 -R 31 is selected from at least 50% and 100%.
12 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 32 -R 36 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:
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 36 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 36 is at least 3%.
16 . An isolated deuterium-enriched compound of claim 15 , wherein the abundance of deuterium in R 1 -R 36 is selected from (a) at least 6%, (b) at least 11%, (c) at least 17%, (d) at least 22%, (e) at least 28%, (f) at least 33%, (g) at least 39%, (h) at least 44%, (i) at least 50%, (j) at least 50%, (k) at least 50%, (l) at least 50%, (m) at least 56%, (n) at least 61%, (o) at least 67%, (p) at least 72%, (q) at least 78%, (r) at least 83%, (s) at least 89%, (t) at least 94%, and (r) 100%.
17 . An isolated deuterium-enriched compound of claim 15 , wherein the abundance of deuterium in R 1 -R 2 is selected from at least 35%, at least 67%, and 100%.
18 . An isolated deuterium-enriched compound of claim 15 , wherein the abundance of deuterium in R 3 -R 4 is selected from at least 50% and 100%.
19 . An isolated deuterium-enriched compound of claim 15 , wherein the abundance of deuterium in R 5 -R 8 is selected from at least 25%, at least 50%, at least 75%, and 100%.
20 . An isolated deuterium-enriched compound of claim 15 , wherein the abundance of deuterium in R 9 -R 10 is selected from at least 50% and 100%.
21 . An isolated deuterium-enriched compound of claim 15 , wherein the abundance of deuterium in R 12 -R 15 is selected from at least 25%, at least 50%, at least 75%, and 100%.
22 . An isolated deuterium-enriched compound of claim 15 , wherein the abundance of deuterium in R 16 -R 19 is selected from at least 25%, at least 50%, at least 75%, and 100%.
23 . An isolated deuterium-enriched compound of claim 15 , wherein the abundance of deuterium in R 20 -R 25 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, and 100%.
24 . An isolated deuterium-enriched compound of claim 15 , wherein the abundance of deuterium in R 26 -R 29 is selected from at least 25%, at least 50%, at least 75%, and 100%.
25 . An isolated deuterium-enriched compound of claim 15 , wherein the abundance of deuterium in R 30 -R 31 is selected from at least 50% and 100%.
26 . An isolated deuterium-enriched compound of claim 15 , wherein the abundance of deuterium in R 32 -R 36 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:
28 . An isolated deuterium-enriched compound of claim 15 , wherein the compound is selected from compounds 12-22 of Table 2:
29 . A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 36 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 36 is at least 3%.
30 . A mixture of deuterium-enriched compound of claim 29 , wherein the abundance of deuterium in R 1 -R 36 is selected from (a) at least 6%, (b) at least 11%, (c) at least 17%, (d) at least 22%, (e) at least 28%, (f) at least 33%, (g) at least 39%, (h) at least 44%, (i) at least 50%, (j) at least 50%, (k) at least 50%, (l) at least 50%, (m) at least 56%, (n) at least 61%, (o) at least 67%, (p) at least 72%, (q) at least 78%, (r) at least 83%, (s) at least 89%, (t) at least 94%, and (r) 100%.
31 . A mixture of deuterium-enriched compound of claim 29 , wherein the abundance of deuterium in R 1 -R 2 is selected from at least 35%, at least 67%, and 100%.
32 . A mixture of deuterium-enriched compound of claim 29 , wherein the abundance of deuterium in R 3 -R 4 is selected from at least 50% and 100%.
33 . A mixture of deuterium-enriched compound of claim 29 , wherein the abundance of deuterium in R 5 -R 9 is selected from at least 25%, at least 50%, at least 75%, and 100%.
34 . A mixture of deuterium-enriched compound of claim 29 , wherein the abundance of deuterium in R 9 -R 10 is selected from at least 50% and 100%.
35 . A mixture of deuterium-enriched compound of claim 29 , wherein the abundance of deuterium in R 12 -R 15 is selected from at least 25%, at least 50%, at least 75%, and 100%.
36 . A mixture of deuterium-enriched compound of claim 29 , wherein the abundance of deuterium in R 16 -R 19 is selected from at least 25%, at least 50%, at least 75%, and 100%.
37 . A mixture of deuterium-enriched compound of claim 29 , wherein the abundance of deuterium in R 20 -R 25 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, and 100%.
38 . A mixture of deuterium-enriched compound of claim 29 , wherein the abundance of deuterium in R 26 -R 29 is selected from at least 25%, at least 50%, at least 75%, and 100%.
39 . A mixture of deuterium-enriched compound of claim 29 , wherein the abundance of deuterium in R 30 -R 31 is selected from at least 50% and 100%.
40 . A mixture of deuterium-enriched compound of claim 29 , wherein the abundance of deuterium in R 32 -R 36 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:
42 . A mixture of deuterium-enriched compound of claim 29 , wherein the compound is selected from compounds 12-22 of Table 2:
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 asthma and/or seasonal allergies 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.