SIRT1 activating compounds
Provided herein are methods and compositions for preventing or treating aging, or an aging-related disorder, a disorder associated with inflammation, or for modulating an immune response in a subject in need thereof. In some embodiments, the methods comprise administering to the subject an effective amount of a compound of Formulas I-XIII.
1. A compound having a structure of Formula I, II or III, or a pharmaceutically acceptable salt thereof:
wherein
Z 1 , Z 2 , Z 3 , and Z 4 are each independently selected from —OC(O)-L 1 -R 1 , —OC(NR 6 )-L 1 -R 1 , and
if the compound has the structure of Formula I, L 1 is a linker group selected from
if the compound has the structure of Formula II or III, L′ is absent or a linker group selected from
R 1 is
R 2 is independently selected from H, optionally substituted alkyl, heteroalkyl, aralkyl, and heteroaralkyl;
R 3 is selected from H, optionally substituted alkyl, heteroalkyl, aryl, and heteroaryl;
R 4 is selected from H, optionally substituted alkyl, heteroalkyl, alkenyl, aryl, and heteroaryl;
R 6 is selected from H and alkyl; and
m, n, p, q are each independently an integer selected from 1 to 10.
2. The compound of claim 1 , wherein the compound has the structure of Formula Ia or a pharmaceutically acceptable salt thereof:
3. The compound of claim 1 , wherein the compound has the structure of Formula Ib or a pharmaceutically acceptable salt thereof:
4. The compound of claim 1 , wherein Z 1 =Z 2 =Z 3 .
5. The compound of claim 1 , wherein Z 1 =Z 2=73 =Z 4 .
6. The compound of claim 1 , wherein R 1 is
7. The compound of claim 1 , wherein n is selected from 3, 4, 5, and 6.
8. The compound of claim 1 , wherein R 4 is straight chained alkyl group having 10 to 20 carbon atoms.
9. The compound of claim 8 , wherein R 4 is
10. The compound of claim 1 , wherein q is 3, 4, or 5.
11. The compound of claim 1 , wherein each R 2 is independently selected from H,
12. The compound of claim 11 , wherein R 2 is selected from H,
13. The compound of claim 1 , wherein Z 1 , Z 2 , and Z 3 are each independently selected from
14. The compound of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
15. The compound of claim 1 , wherein the compound has the structure of Formula II or III.
16. The compound of claim 15 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
17. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
18. A method for treating aging, or an aging-related disorder, in a subject in need thereof comprising administering to the subject an effective amount of a compound of claim 1 .
19. A method for treating a disorder associated with inflammation in a subject in need thereof comprising administering to the subject an effective amount a compound of claim 1 .