DEUTERIUM-ENRICHED PRAVASTATIN
The present application describes deuterium-enriched pravastatin, 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 35 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 35 is at least 3%.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 35 is selected from at least 3%, at least 6%, at least 11%, at least 17%, at least 23%, at least 29%, at least 34%, at least 40%, at least 46%, at least 51%, at least 57%, at least 63%, at least 69%, at least 74%, at least 80%, at least 85%, at least 95%, at least 97%, and 100%.
3 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 3 is selected from at least 33%, at least 67%, and 100%.
4 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 4 -R 11 , R 22 -R 23 , and R 33 -R 34 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 12 -R 21 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%.
6 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 24 -R 34 is selected from at least 11%, at least 22%, at least 33%, at least 44%, at least 56%, at least 67%, at least 78%, 100%.
7 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-5 of Table 1.
8 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 6-10 of Table 2.
9 . An isolated deuterium-enriched compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 35 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 35 is at least 3%.
10 . An isolated deuterium-enriched compound of claim 9 , wherein the abundance of deuterium in R 1 -R 35 is selected from at least 3%, at least 6%, at least 11%, at least 17%, at least 23%, at least 29%, at least 34%, at least 40%, at least 46%, at least 51%, at least 57%, at least 63%, at least 69%, at least 74%, at least 80%, at least 85%, at least 95%, at least 97%, and 100%.
11 . An isolated deuterium-enriched compound of claim 9 , wherein the abundance of deuterium in R 1 -R 3 is selected from at least 33%, at least 67%, and 100%.
12 . An isolated deuterium-enriched compound of claim 9 , wherein the abundance of deuterium in R 4 -R 11 , R 22 -R 23 , and R 33 -R 34 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%.
13 . An isolated deuterium-enriched compound of claim 9 , wherein the abundance of deuterium in R 12 -R 21 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%.
14 . An isolated deuterium-enriched compound of claim 9 , wherein the abundance of deuterium in R 24 -R 34 is selected from at least 11%, at least 22%, at least 33%, at least 44%, at least 56%, at least 67%, at least 78%, 100%.
15 . An isolated deuterium-enriched compound of claim 9 , wherein the compound is selected from compounds 1-5 of Table 1.
16 . An isolated deuterium-enriched compound of claim 9 , wherein the compound is selected from compounds 6-10 of Table 2.
17 . A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 35 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 35 is at least 3%.
18 . A mixture of deuterium-enriched compound of claim 17 , wherein the compound is selected from compounds 1-5 of Table 1.
19 . A mixture of deuterium-enriched compound of claim 17 , wherein the compound is selected from compounds 6-10 of Table 2.
20 . 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.
21 . A method for treating hypercholesterolemia 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.