Deuterium-enriched capecitabine
The present application describes deuterium-enriched capecitabine, 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 22 are independently selected from H and D; and the abundance of deuterium in R 1 -R 22 is at least 5%.
2. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 22 is selected from at least 5%, at least 9%, at least 14%, at least 18%, at least 23%, at least 27%, at least 32%, at least 36%, at least 41%, at least 45%, at least 50%, at least 55%, at least 59%, at least 64%, at least 68%, at least 73%, at least 77%, at least 82%, at least 86%, at least 91%, at least 95%, 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 6 is selected from at least 33%, at least 67%, and 100%.
5. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 7 -R 10 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 11 is 100%.
7. 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%.
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 22 are independently selected from H and D; and the abundance of deuterium in R 1 -R 22 is at least 5%.
11. An isolated deuterium-enriched compound of claim 10 , wherein the abundance of deuterium in R 1 -R 22 is selected from at least 5%, at least 9%, at least 14%, at least 18%, at least 23%, at least 27%, at least 32%, at least 36%, at least 41%, at least 45%, at least 50%, at least 55%, at least 59%, at least 64%, at least 68%, at least 73%, at least 77%, at least 82%, at least 86%, at least 91%, at least 95%, 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 6 is selected from at least 33%, at least 67%, 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 22 are independently selected from H and D; and the abundance of deuterium in R 1 -R 22 is at least 5%.
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 metastatic breast cancer 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.