DEUTERIUM-ENRICHED PACLITAXEL
The present application describes deuterium-enriched paclitaxel, 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 51 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 51 is at least 2%.
2 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 51 is selected from at least 2%, at least 4%, at least 10%, at least 16%, at least 22%, at least 27%, at least 33%, at least 39%, at least 45%, at least 51%, at least 57%, at least 63%, at least 69%, at least 75%, at least 80%, at least 86%, at least 92%, at least 98%, 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 -R 9 is selected from at least 20%, at least 40%, at least 60%, at least 80%, and 100%.
5 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 10 and R 16 is selected from at least 50% and 100%.
6 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 11 -R 15 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 22 -R 24 is selected from at least 33%, at least 67%, and 100%.
8 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 34 -R 36 is selected from at least 33%, at least 67%, and 100%.
9 . A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 39 -R 43 is selected from at least 20%, at least 40%, at least 60%, at least 80%, and 100%.
10 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-8 of Table 1.
11 . A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 9-16 of Table 2.
12 . An isolated deuterium-enriched compound of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 51 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 51 is at least 2%.
13 . An isolated deuterium-enriched compound of claim 12 , wherein the abundance of deuterium in R 1 -R 51 is selected from at least 2%, at least 4%, at least 10%, at least 16%, at least 22%, at least 27%, at least 33%, at least 39%, at least 45%, at least 51%, at least 57%, at least 63%, at least 69%, at least 75%, at least 80%, at least 86%, at least 92%, at least 98%, and 100%.
14 . An isolated deuterium-enriched compound of claim 12 , wherein the compound is selected from compounds 1-8 of Table 1.
15 . An isolated deuterium-enriched compound of claim 12 , wherein the compound is selected from compounds 9-16 of Table 2.
16 . A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 51 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 51 is at least 2%.
17 . A mixture of deuterium-enriched compound of claim 16 , wherein the compound is selected from compounds 1-8 of Table 1.
18 . A mixture of deuterium-enriched compound of claim 16 , wherein the compound is selected from compounds 9-16 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 a disease selected from Kaposi's sarcoma and/or cancer of the lung, ovarian, and breast 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.