Deuterated melflufen compounds
The invention provides a compound of formula (I), or a pharmaceutically acceptable salt thereof (Formula I), wherein, each R 1 -R 30 is independently selected from the group consisting of H and deuterium, and at least one of R 1 -R 30 is deuterium with an abundance level greater than the naturally occurring abundance of deuterium. The invention also provides pharmaceutical compositions containing the compounds, and uses of the compounds.
1. A compound of formula (I), or a pharmaceutically acceptable salt thereof,
wherein,
each R 9 -R 30 is independently selected from the group consisting of H and deuterium, and at least one of R 9 -R 30 is deuterium with an abundance level of at least 1 mol %, 5 mol %, 10 mol %, 50 mol %, 90 mol % or 98 mol % deuterium; and
each R 1 -R 8 is H.
2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein at least one of R 9 -R 15 is deuterium with an abundance level of at least 5 mol %.
3. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein at least one of R 16 -R 18 is deuterium with an abundance level of at least 5 mol %.
4. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein at least one of R 19 -R 25 is deuterium with an abundance level of at least 5 mol %.
5. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein at least one of R 26 -R 30 is deuterium with an abundance level of at least 5 mol %.
6. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein at least two of R 26 -R 30 is deuterium.
7. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the abundance level is at least 10 mol %, 50 mol %, 90 mol % or 98 mol % deuterium.
8. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound has a structural formula according to:
9. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound has a structural formula according to:
10. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound has a structural formula selected from the group consisting of:
11. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound has a structural formula according to:
12. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound has a structural formula according to:
13. A pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier.
14. The pharmaceutical composition of claim 13 , which further comprises a protease inhibitor (PI), an immunomodulatory drug (IMiD) or an alkylator.
15. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, having a structure of formula (Ia):
16. The compound of claim 1 , wherein the compound is ( 2 H 5 ) ethyl (2S)-2-[(2S)-2-amino-3-{4-[bis (2-chloroethyl) amino] phenyl} propanamido]-3-(4-fluorophenyl) propanoate hydrochloride.
17. A compound having a structural formula according to:
or a pharmaceutically acceptable salt thereof.