Tetrahydrocarbazole inhibitors of SIRT1 receptors
Described are deuterium-substituted tetrahydrocarbazole compounds of Formulae I, II, or III which are inhibitors of sirtuin 1 (SIRT1). Also described are pharmaceutical compositions comprising the deuterium-substituted tetrahydrocarbazole compounds, and methods of use thereof.
1. A compound of Formula III:
or a salt, prodrug, or solvate thereof, wherein:
R 1 -R 7 are, independently, hydrogen or deuterium;
at least one of R 1 -R 7 is deuterium; and
at least one of R 1 -R 7 has deuterium enrichment of no less than about 10%.
2. The compound of claim 1 , wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are deuterium.
3. The compound of claim 1 , wherein R 7 is deuterium.
4. The compound of claim 1 , wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are deuterium.
5. The compound of claim 1 , wherein at least one of R 1 -R 7 has deuterium enrichment of no less than about 50%.
6. The compound of claim 1 , wherein at least one of R 1 -R 7 has deuterium enrichment of no less than about 90%.
7. The compound of claim 1 , wherein at least one of R 1 -R 7 has deuterium enrichment of no less than about 98%.
8. The compound of claim 1 , wherein the compound is:
or a salt, prodrug, or solvate thereof.
9. The compound of claim 8 , which is:
or a salt, prodrug, or solvate thereof.
10. The compound of claim 8 , wherein each position represented as D has deuterium enrichment of no less than about 10%.
11. The compound of claim 10 , wherein each position represented as D has deuterium enrichment of no less than about 50%.
12. The compound of claim 11 , wherein each position represented as D has deuterium enrichment of no less than about 90%.
13. The compound of claim 12 , wherein each position represented as D has deuterium enrichment of no less than about 98%.
14. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.