DEUTERIUM-ENRICHED OLOPATADINE
The present application describes deuterium-enriched olopatadine, 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 at least 4%. The abundance can also be (a) at least 9%, (b) at least 13%, (c) at least 17%, (d) at least 22%, (e) at least 26%, (f) at least 30%, (g) at least 35%, (h) at least 39%, (i) at least 43%, 0) at least 48%, (k) at least 52%, (l) at least 57%, (m) at least 61%, (n) at least 65%, (o) at least 70%, (p) at least 74%, (q) at least 78%, (r) at least 83%, (s) at least 87%, (t) at least 91%, (u) at least 96%, and (v) 100%.
3 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 is selected from at least 100%.
4 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 2 -R 9 and R 12 is selected from at least 8%, at least 15%, at least 24%, 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%.
5 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 10 -R 11 is selected from at least 8%, at least 17%, at least 25%, at least 34%, at least 42%, at least 50%, at least 58%, at least 67%, at least 75%, at least 84%, at least 92%, and 100%.
6 . A deuterium-enriched compound of claim 1 , 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%.
7 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 18 -R 20 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 74%, at least 82%, at least 91%, and 100%.
8 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 21 -R 23 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 74%, at least 82%, at least 91%, and 100%.
9 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-7 of Table 1.
10 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 8-14 of Table 2.
11 . 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 4%.
12 . An isolated deuterium-enriched compound of claim 11 , wherein the abundance of deuterium in R 1 -R 23 is at least 4%. The abundance can also be (a) at least 9%, (b) at least 13%, (c) at least 17%, (d) at least 22%, (e) at least 26%, (f) at least 30%, (g) at least 35%, (h) at least 39%, (i) at least 43%, (j) at least 48%, (k) at least 52%, (l) at least 57%, (m) at least 61%, (n) at least 65%, (o) at least 70%, (p) at least 74%, (q) at least 78%, (r) at least 83%, (s) at least 87%, (t) at least 91%, (u) at least 96%, and (v) 100%.
13 . An isolated deuterium-enriched compound of claim 11 , wherein the abundance of deuterium in R 1 is selected from at least 100%.
14 . An isolated deuterium-enriched compound of claim 11 , wherein the compound is selected from compounds 1-7 of Table 1.
15 . An isolated deuterium-enriched compound of claim 11 , wherein the compound is selected from compounds 8-14 of Table 2.
16 . 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%.
17 . A mixture of deuterium-enriched compound of claim 16 , wherein the compound is selected from compounds 1-7 of Table 1.
18 . A mixture of deuterium-enriched compound of claim 16 , wherein the compound is selected from compounds 8-14 of Table 2.
19 . 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.
20 . A method for treating allergic conjunctivitis, 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.