Prodrugs of gamma-hydroxybutyric acid, compositions and uses thereof
The present disclosure discloses prodrugs of gamma-hydroxybutyric acid as well as compositions and uses thereof.
1. A compound having the chemical structure shown in Formula (IA):
or a pharmaceutically acceptable salt thereof, wherein,
R g is hydrogen or C 1 alkyl; and
R h and R f are independently hydrogen, unsubstituted C 1-6 alkyl, C 1-6 alkoxylcarbonyl, or C 3-6 cycloalkoxylcarbonyl.
2. The compound of claim 1 , wherein at least one of R h and R f is hydrogen or C 1-3 alkyl.
3. The compound of claim 2 , wherein both R h and R f are hydrogen or C 1-3 alkyl.
4. The compound of claim 1 , wherein R f is —COR 5 , and R 5 is C 1-3 alkoxyl or C 5-6 cycloalkyloxyl.
5. The compound of claim 1 , wherein both R h and R f are hydrogen.
6. The compound of claim 5 , wherein the molecular weight of the compound is no more than 450 Da.
7. The compound of claim 5 , wherein a hydrogen comprises protium or deuterium.
8. The compound of claim 5 , wherein the compound can be converted to gamma-hydroxybutyric acid and enter into the human circulatory system through a biological process after oral administration.
9. A method of treating a subject in need thereof, wherein the method comprises administering to the subject a pharmaceutically effective amount of the compound of claim 5 , wherein the subject suffers from a disease or condition selected from narcolepsy, excessive daytime sleepiness, cataplexy, fibromyalgia, chronic fatigue, and tardive dyskinesia.
10. The method of claim 9 , wherein the disease or condition is narcolepsy, excessive daytime sleepiness, or cataplexy.
11. The method of claim 9 , wherein the administration is conducted no more than two times per day.
12. The method of claim 9 , wherein the administration is via oral administration.
13. The method of claim 9 , wherein the compound is formulated in a unit dosage form.
14. The method of claim 12 , wherein administering the compound orally comprises administering the compound in an emulsion, syrup, elixir, suspension, slurry, or solution.
15. A pharmaceutical composition comprising:
the compound of claim 1 or a pharmaceutically acceptable salt thereof; and
a pharmaceutically acceptable carrier.
16. The pharmaceutical composition of claim 15 , wherein both R h and R f are hydrogen.
17. The pharmaceutical composition of claim 16 , wherein the pharmaceutical composition is a solid.
18. The pharmaceutical composition of claim 16 , wherein the pharmaceutically acceptable carrier comprises a solvent for dissolving or dispersing the compound.
19. The pharmaceutical composition of claim 16 , wherein the pharmaceutical composition is formulated in a unit dosage form.
20. The pharmaceutical composition of claim 19 , wherein the compound of Formula (IA) is present in the unit dosage form in an amount from 1 gram to 18 grams.
21. The pharmaceutical composition of claim 15 , wherein the pharmaceutical composition is formulated in a sustained release form.
22. The method of claim 10 , wherein the disease or condition is narcolepsy.
23. The method of claim 10 , wherein the disease or condition is excessive daytime sleepiness.
24. The method of claim 10 , wherein the disease or condition is cataplexy.
25. The method of claim 14 , wherein administering the compound orally comprises administering the compound in a solution.
26. The method of claim 13 , wherein the compound of Formula (IA) is present in the unit dosage form in an amount from 1 gram to 18 grams.
27. The compound of claim 1 , wherein the compound is selected from the group consisting of:
28. The pharmaceutical composition of claim 15 , wherein the pharmaceutical composition is formulated for oral administration.
29. The pharmaceutical composition of claim 15 , wherein the pharmaceutical composition is formulated in a liquid dosage form.
30. The compound of claim 5 , wherein the compound is
31. The compound of claim 5 , wherein the compound is
32. The method of claim 9 , wherein the administration is via oral, nasal, intravenous, subcutaneous, or intramuscular administration.