Deuterium-enriched nelarabine
The present application describes deuterium-enriched nelarabine, 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 15 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 15 is at least 7%.
2. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 15 is at least 7%. The abundance can also be (a) at least 13%, (b) at least 20%, (c) at least 27%, (d) at least 33%, (e) at least 40%, (f) at least 47%, (g) at least 53%, (h) at least 60%, (i) at least 67%, (j) at least 73%, (k) at least 80%, (l) at least 87%, (m) at least 93%, and (n) 100%.
3. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 1 -R 5 is at least 20%. The abundance can also be (a) at least 40%, (b) at least 60%, (c) at least 80%, and (d) 100%.
4. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 6 -R 8 is at least 33%. The abundance can also be (a) at least 67%, and (b) 100%.
5. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 9 is selected from 100%.
6. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R 10 -R 15 is at least 17%. The abundance can also be (a) at least 33%, (b) at least 50%, (c) at least 67%, (d) at least 83%, and (e) 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 15 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 15 is at least 7%.
10. An isolated deuterium-enriched compound of claim 9 , wherein the abundance of deuterium in R 1 -R 15 is at least 7%. The abundance can also be (a) at least 13%, (b) at least 20%, (c) at least 27%, (d) at least 33%, (e) at least 40%, (f) at least 47%, (g) at least 53%, (h) at least 60%, (i) at least 67%, (j) at least 73%, (k) at least 80%, (l) at least 87%, (m) at least 93%, and (n) 100%.
11. An isolated deuterium-enriched compound of claim 9 , wherein the abundance of deuterium in R 1 -R 5 is at least 20%. The abundance can also be (a) at least 40%, (b) at least 60%, (c) at least 80%, and (d) 100%.
12. An isolated deuterium-enriched compound of claim 9 , wherein the abundance of deuterium in R 6 -R 8 is at least 33%. The abundance can also be (a) at least 67%, and (b) 100%.
13. An isolated deuterium-enriched compound of claim 9 , wherein the abundance of deuterium in R 9 is selected from 100%.
14. An isolated deuterium-enriched compound of claim 9 , wherein the compound is selected from compounds 1-5 of Table 1.
15. An isolated deuterium-enriched compound of claim 9 , wherein the compound is selected from compounds 6-10 of Table 2.
16. A mixture of deuterium-enriched compounds of formula I or a pharmaceutically acceptable salt thereof:
wherein R 1 -R 15 are independently selected from H and D; and
the abundance of deuterium in R 1 -R 15 is at least 7%.
17. A mixture of deuterium-enriched compound of claim 16 , wherein the compound is selected from compounds 1-5 of Table 1.
18. A mixture of deuterium-enriched compound of claim 16 , wherein the compound is selected from compounds 6-10 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 leukemia 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.