Nicotinamide mononucleotide derivatives and their uses
The invention relates to compositions of nicotinamide mononucleotide derivatives and their methods of use. The invention also relates to methods of preparing nicotinamide mononucleotide derivatives. The invention relates to pharmaceutical compositions and nutritional supplements containing a nicotinamide mononucleotide derivative. The invention relates to methods of using nicotinamide mononucleotide derivatives that promote the increase of intracellular levels of nicotinamide adenine dinucleotide (NAD+) in cells and tissues for treating diseases and improving cell and tissue survival.
1. A compound, or a salt thereof, wherein the compound is represented by formula III:
wherein W 1 and W 2 are each independently O − or OR 5 , and each R 5 is independently hydrogen or unsubstituted or substituted alkyl; provided that
a) when W 1 is O − or OH, and W 2 is OR 5 , then R 5 is not hydrogen, methyl or butyl;
b) when W 1 is O − or OH, W 2 is OR 5 , and R 5 is substituted alkyl, then the substituent is selected from halo, CN, NO 2 , alkenyl, C 9-16 alkoxy, —C(O)—O-alkyl, —C(O)—O-aryl, —O—C(O)-alkyl, —O—C(O)-aryl, —S—C(O)-alkyl, and heterocyclyl; and
c) W 1 and W 2 are not each OMe.
2. The compound of claim 1 , wherein W 2 is OR 5 and R 5 is unsubstituted alkyl.
3. The compound of claim 1 , wherein W 2 is OR 5 and R 5 is substituted alkyl.
4. The compound of claim 3 , wherein the substituted alkyl has a substituent selected from halo, CN, NO 2 , alkenyl, alkynyl, C 9-16 alkoxy, —C(O)—O-alkyl, —C(O)—O-aryl, —O—C(O)-alkyl, —O—C(O)-aryl, —S—C(O)-alkyl, heterocyclyl, carbocyclyl, aryl and heteroaryl.
5. The compound of claim 4 , wherein the substituted alkyl has a substituent that is C 9-16 alkoxy or —S—C(O)-alkyl.
6. The compound of claim 1 , wherein both W 1 and W 2 are OR 5 .
7. The compound of claim 6 , wherein each R 5 is substituted C 2-4 alkyl.
8. The compound of claim 7 , wherein each R 5 is ethyl substituted with a —S—C(O)-alkyl.
9. The compound of claim 6 , wherein W 1 is OMe, and W 2 is OR 5 and R 5 is substituted alkyl.
10. The compound of claim 9 , wherein R 5 is an alkyl substituted with an alkoxy.
11. The compound of claim 10 , wherein R 5 is an alkyl substituted with a C 9 alkoxy.
12. The compound of claim 10 , wherein R 5 is an alkyl substituted with a C 15 alkoxy.
13. The compound of claim 9 , wherein R 5 is substituted propyl.
14. The compound of claim 13 , wherein the propyl group is substituted with an alkoxy.
15. The compound of 14 , wherein the propyl group is substituted with a C 9 alkoxy.
16. The compound of 14 , wherein the propyl group is substituted with a C 15 alkoxy.
17. The compound of claim 1 , wherein W 1 is O − and W 2 is OR 5 .
18. The compound of claim 17 , wherein R 5 is substituted alkyl.
19. The compound of claim 18 , wherein R 5 is an alkyl substituted with a C 9-16 alkoxy.
20. The compound of claim 19 , wherein R 5 is an alkyl substituted with a C 9 alkoxy.
21. The compound of claim 19 , wherein R 5 is an alkyl substituted with a C 15 alkoxy.
22. The compound of claim 18 , wherein R 1 is a propyl group substituted with a C 9-16 alkoxy.
23. The compound of 22 , wherein the propyl group is substituted with a C 9 alkoxy.
24. The compound of 22 , wherein the propyl group is substituted with a C 15 alkoxy.
25. A compound selected from
or a salt thereof.
26. The compound of claim 1 , wherein the salt is formed with an anion selected from acetate, triflate, halide, trifluoroacetate, and formate.
27. The compound of claim 1 , wherein the salt is formed with an anion selected from OH − , H 2 PO 4 − , HPO 4 2− , HSO 4 − , SO 4 2− , NO 3 − , HCO 3 − , and CO 3 2− .
28. The compound of claim 1 , wherein the salt is formed with a cation selected from Na + , K + , Mg 2+ , and Ca 2+ .
29. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.