2,6-dioxo-3-deutero-piperdin-3-yl-isoindoline compounds
The present application describes 2-(2′,6′-dioxo-3′-deutero-piperidin-3′-yl)isoindoles, deuterated derivatives thereof, stereoisomers thereof, pharmaceutically acceptable salt forms thereof, and methods of treating using the same.
1. A deuterium-enriched compound of formula II, or a stereoisomer or pharmaceutically acceptable salt thereof:
wherein:
Z is H or D, provided that the abundance of deuterium in Z is at least 30%;
R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are independently selected from H and D; and
R 12a -R 12ee are independently selected from H and D.
2. A deuterium-enriched compound of claim 1 , wherein the compound is of formula IIa, or pharmaceutically acceptable salt thereof:
wherein:
R 12a -R 12ee are independently selected from H and D.
3. A deuterium-enriched compound of claim 1 , wherein the compound is of formula IIb, or a pharmaceutically acceptable salt thereof:
wherein:
R 12a -R 12e are independently selected from H and D.
4. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in Z is at least 80%.
5. A deuterium-enriched compound of claim 1 , wherein the compound is of formula II 1 , or a stereoisomer or pharmaceutically acceptable salt thereof:
wherein the abundance of deuterium in Z is selected from: (a) at least 40%, (b) at least 50%, (c) at least 60%, (d) at least 70%, (e) at least 80%, (f) at least 90%, (g) at least 95%, (h) at least 97%, and (i) about 100%.
6. A deuterium-enriched compound of claim 1 , wherein the compound is of formula IIa 1 , or pharmaceutically acceptable salt thereof:
wherein the abundance of deuterium in Z is selected from: (a) at least 40%, (b) at least 50%, (c) at least 60%, (d) at least 70%, (e) at least 80%, (f) at least 90%, (g) at least 95%, (h) at least 97%, and (i) about 100%.
7. A deuterium-enriched compound of claim 1 , wherein the compound is of formula IIb 1 , or pharmaceutically acceptable salt thereof:
wherein the abundance of deuterium in Z is selected from: (a) at least 40%, (b) at least 50%, (c) at least 60%, (d) at least 70%, (e) at least 80%, (f) at least 90%, (g) at least 95%, (h) at least 97%, and (i) about 100%.
8. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 1 .
9. A method for treating myelodysplastic syndrome comprising: administering, to a patient in need thereof, a therapeutically effective amount of a compound of claim 1 to treat the myelodysplatic syndrome.
10. The deuterium-enriched compound of claim 5 , wherein the compound is a compound of formula II 1 or a stereoisomer thereof.
11. The deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in Z is at least 90%.
12. The deuterium-enriched compound of claim 5 , wherein the abundance of deuterium in Z is at least 90%.
13. The deuterium-enriched compound of claim 5 , wherein the abundance of deuterium in Z is at least 95%.
14. The deuterium-enriched compound of claim 6 , wherein the abundance of deuterium in Z is at least 90%.
15. The deuterium-enriched compound of claim 6 , wherein the abundance of deuterium in Z is at least 95%.
16. The deuterium-enriched compound of claim 7 , wherein the abundance of deuterium in Z is at least 90%.
17. The deuterium-enriched compound of claim 7 , wherein the abundance of deuterium in Z is at least 95%.
18. The deuterium-enriched compound of claim 10 , wherein the abundance of deuterium in Z is at least 90%.
19. A pharmaceutical composition comprising a compound of claim 5 and one or more excipients.
20. A pharmaceutical composition comprising a compound of claim 11 and one or more excipients.
21. A pharmaceutical composition comprising a compound of claim 12 and one or more excipients.
22. A pharmaceutical composition comprising a compound of claim 14 and one or more excipients.
23. A pharmaceutical composition comprising a compound of claim 16 and one or more excipients.