DEUTERIUM-ENRICHED CLOPIDOGREL
The present application describes deuterium-enriched clopidogrel, 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 16 are independently selected from H and D; and the abundance of deuterium in R 1 -R 16 is at least 6%.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 16 is selected from at least 6%, at least 13%, at least 19%, at least 25%, at least 31%, at least 38%, at least 44%, at least 50%, at least 56%, at least 63%, at least 69%, at least 75%, at least 81%, at least 88%, at least 94%, and 100%.
3 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 4 is selected from at least 25%, at least 50%, at least 75%, and 100%.
4 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 5 is selected from 100%.
5 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 6 -R 8 is selected from at least 33%, at least 67%, and 100%.
6 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 9 -R 14 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, and 100%.
7 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 15 -R 16 is selected from at least 50% and 100%.
8 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-10 of Table 1:
9 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 11-20 of Table 2:
10 . An isolated deuterium-enriched compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 16 are independently selected from H and D; and the abundance of deuterium in R 1 -R 16 is at least 6%.
11 . An isolated deuterium-enriched compound of claim 10 , wherein the abundance of deuterium in R 1 -R 16 is selected from at least 6%, at least 13%, at least 19%, at least 25%, at least 31%, at least 38%, at least 44%, at least 50%, at least 56%, at least 63%, at least 69%, at least 75%, at least 81%, at least 88%, at least 94%, and 100%.
12 . An isolated deuterium-enriched compound of claim 10 , wherein the abundance of deuterium in R 1 -R 4 is selected from at least 25%, at least 50%, at least 75%, and 100%.
13 . An isolated deuterium-enriched compound of claim 10 , wherein the abundance of deuterium in R 5 is selected from 100%.
14 . An isolated deuterium-enriched compound of claim 10 , wherein the abundance of deuterium in R 6 -R 8 is selected from at least 33%, at least 67%, and 100%.
15 . An isolated deuterium-enriched compound of claim 10 , wherein the abundance of deuterium in R 9 -R 14 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 10 , wherein the abundance of deuterium in R 15 -R 16 is selected from at least 50% and 100%.
17 . An isolated deuterium-enriched compound of claim 10 , wherein the compound is selected from compounds 1-10 of Table 1:
18 . An isolated deuterium-enriched compound of claim 10 , wherein the compound is selected from compounds 11-20 of Table 2:
19 . A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 16 are independently selected from H and D; and the abundance of deuterium in R 1 -R 16 is at least 6%.
20 . A mixture of deuterium-enriched compound of claim 19 , wherein the abundance of deuterium in R 1 -R 16 is selected from at least 6%, at least 13%, at least 19%, at least 25%, at least 31%, at least 38%, at least 44%, at least 50%, at least 56%, at least 63%, at least 69%, at least 75%, at least 81%, at least 88%, at least 94%, and 100%.
21 . A mixture of deuterium-enriched compound of claim 19 , wherein the abundance of deuterium in R 1 -R 4 is selected from at least 25%, at least 50%, at least 75%, and 100%.
22 . A mixture of deuterium-enriched compound of claim 19 , wherein the abundance of deuterium in R 5 is selected from 100%.
23 . A mixture of deuterium-enriched compound of claim 19 , wherein the abundance of deuterium in R 6 -R 8 is selected from at least 33%, at least 67%, and 100%.
24 . A mixture of deuterium-enriched compound of claim 19 , wherein the abundance of deuterium in R 9 -R 14 is selected from at least 17%, at least 33%, at least 50%, at least 67%, at least 83%, and 100%.
25 . A mixture of deuterium-enriched compound of claim 19 , wherein the abundance of deuterium in R 15 -R 16 is selected from at least 50% and 100%.
26 . A mixture of deuterium-enriched compound of claim 19 , wherein the compound is selected from compounds 1-10 of Table 1:
27 . A mixture of deuterium-enriched compound of claim 19 , wherein the compound is selected from compounds 11-20 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 coronary artery disease, peripheral vascular disease, cerebrovascular disease, or combination thereof, 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.