Deuterium-enriched topotecan
The present application describes deuterium-enriched topotecan, 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 23 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 23 is at least 4%.
2. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 23 is selected from at least 4%, at least 9%, at least 13%, at least 17%, at least 22%, at least 26%, at least 30%, at least 35%, at least 39%, at least 43%, at least 48%, at least 52%, at least 57%, at least 61%, at least 65%, at least 70%, at least 74%, at least 78%, at least 83%, at least 87%, at least 91%, at least 96%, and 100%.
3. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 2 is selected from at least 50% and 100%.
4. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 3 -R 4 and R 15 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 16 -R 17 is selected from at least 50% and 100%.
6. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 18 -R 23 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 13 -R 14 is selected from at least 50% and 100%.
8. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 5 and R 11 -R 12 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 6 -R 10 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;
1
2
3
4
5
6
7
8
or a pharmaceutically acceptable salt thereof, wherein when one of R 1 -R 23 is present, it is selected from H or D.
11. A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 9-16;
9
10
11
12
13
14
15
16
or a pharmaceutically acceptable salt thereof.
12. A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 23 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 23 is at least 4%.
13. A mixture of deuterium-enriched compound of claim 12 , wherein the compound is selected from compounds 1-8;
1
2
3
4
5
6
7
8
or a pharmaceutically acceptable salt thereof, wherein when one of R 1 -R 23 is present, it is selected from H or D.
14. A mixture of deuterium-enriched compound of claim 12 , wherein the compound is selected from compounds 9-16;
9
10
11
12
13
14
15
16
or a pharmaceutically acceptable salt thereof.
15. 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.
16. A method for treating 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.
17. A compound of claim 1 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.
18. A compound of claim 1 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.
19. A compound of claim 1 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.
20. A compound of claim 1 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.
21. A compound of claim 1 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.
22. A compound of claim 1 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.
23. A compound of claim 1 , wherein the compound is of the formula:
or a pharmaceutically acceptable salt thereof.