DEUTERIUM-ENRICHED FLUVASTATIN
The present application describes deuterium-enriched fluvastatin, 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 26 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 26 is at least 4%.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 26 is selected from at least 4%, at least 8%, at least 12%, at least 15%, at least 19%, at least 23%, at least 27%, at least 31%, at least 35%, at least 38%, at least 42%, at least 46%, at least 50%, at least 54%, at least 58, at least 62%, at least 65%, at least 69%, at least 73%, at least 77%, at least 81%, at least 85%, at least 88%, at least 92%, at least 96%, 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 10 is selected from at least 14%, at least 29%, at least 43%, at least 57%, at least 71%, at least 86%, and 100%.
5 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 11 -R 14 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 18 is selected from at least 25%, at least 50%, at least 75%, and 100%.
7 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 19 -R 26 is selected from at least 13%, at least 25%, at least 38%, at least 50%, at least 63%, at least 75%, at least 88%, and 100%.
8 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-6 of Table 1.
9 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 7-12 of Table 2.
10 . An isolated deuterium-enriched compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 26 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 26 is at least 4%.
11 . An isolated deuterium-enriched compound of claim 10 , wherein the abundance of deuterium in R 1 -R 26 is selected from at least 4%, at least 8%, at least 12%, at least 15%, at least 19%, at least 23%, at least 27%, at least 31%, at least 35%, at least 38%, at least 42%, at least 46%, at least 50%, at least 54%, at least 58, at least 62%, at least 65%, at least 69%, at least 73%, at least 77%, at least 81%, at least 85%, at least 88%, at least 92%, at least 96%, and 100%.
12 . An isolated deuterium-enriched compound of claim 10 , wherein the abundance of deuterium in R 1 -R 3 is selected from at least 33%, at least 67%, and 100%.
13 . An isolated deuterium-enriched compound of claim 10 , wherein the abundance of deuterium in R 4 -R 10 is selected from at least 14%, at least 29%, at least 43%, at least 57%, at least 71%, at least 86%, and 100%.
14 . An isolated deuterium-enriched compound of claim 10 , wherein the compound is selected from compounds 1-6 of Table 1.
15 . An isolated deuterium-enriched compound of claim 10 , wherein the compound is selected from compounds 7-12 of Table 2.
16 . A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 26 are independently selected from H and D; and the abundance of deuterium in R 1 -R 26 is at least 4%.
17 . A mixture of deuterium-enriched compound of claim 16 , wherein the compound is selected from compounds 1-6 of Table 1.
18 . A mixture of deuterium-enriched compound of claim 16 , wherein the compound is selected from compounds 7-12 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 hypercholesterolemia and/or to prevent cardiovascular disease 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.