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 method of treating a disease in a patient, wherein the disease is selected from excessive daytime sleepiness in a patient with Parkinson's disease or chronic fatigue in a patient with Parkinson's disease, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of Formula (IA):
or a pharmaceutically acceptable salt thereof, wherein,
R g is selected from hydrogen and C 1-6 alkyl; and
each of R h and R f is independently selected from hydrogen, C 1-6 alkyl, C 1-6 alkoxylcarbonyl, and C 3-6 cycloalkoxylcarbonyl.
2. The method of claim 1 , wherein R g is selected from hydrogen and C 1-3 alkyl.
3. The method of claim 1 , wherein at least one of R h and R f is selected from hydrogen and C 1-3 alkyl.
4. The method of claim 1 , wherein each of R h and R f is selected from hydrogen and C 1-3 alkyl.
5. The method of claim 1 , wherein,
R h is selected from hydrogen and C 1-3 alkyl; and
R f is —COR 5 , wherein R 5 is selected from C 1-3 alkoxyl and C 54 cycloalkyloxyl.
6. The method of claim 1 , wherein,
each of R h and R f is hydrogen; and
R g is selected from hydrogen and C 1-3 alkyl.
7. The method of claim 1 , wherein the carbon atom to which R g is bonded is in the (R)-configuration.
8. The method of claim 1 , wherein the carbon atom to which R g is bonded is in the (S)-configuration.
9. The method of claim 1 , wherein the compound is selected from:
4-(((tert-butoxycarbonyl)glycyl)oxy)butanoic acid;
4-(glycyloxy)butanoic acid;
4-((D-valyl)oxy)butanoic acid;
4-((L-alanyl)oxy)butanoic acid;
4-(((ethoxycarbonyl)glycyl)oxy)butanoic acid;
4-(((isopropoxycarbonyl)glycyl)oxy)butanoic acid;
4-((((cyclohexyloxy)carbonyl)glycyl)oxy)butanoic acid;
4-(((ethoxycarbonyl)-D-valyl)oxy)butanoic acid;
4-((L-valyl)oxy)butanoic acid;
a pharmaceutically acceptable salt of any of the foregoing;
and a combination of any of the foregoing.
10. The method of claim 1 , wherein the compound is 4-((L-valyl)oxy)butanoic acid (IIA) or a pharmaceutically acceptable salt thereof:
11. The method of claim 1 , wherein the compound is 4-(glycyloxy)buatanoic acid (IIB) or a pharmaceutically acceptable salt thereof:
12. The method of claim 1 , wherein the compound is 4-((L-alanyl)oxy)butanoic acid (IIC) or a pharmaceutically acceptable salt thereof:
13. The method of claim 1 , wherein administering comprises orally administering.
14. The method of claim 1 , wherein administering comprises administering a pharmaceutical composition comprising the compound of Formula (IA) or a pharmaceutically acceptable salt thereof.
15. The method of claim 1 , wherein the pharmaceutical composition comprises an oral formulation.
16. The method of claim 1 , wherein the pharmaceutical composition comprises an oral dosage form.
17. The method of claim 1 , wherein the pharmaceutical composition comprises a sustained release oral formulation.
18. The method of claim 1 , wherein the pharmaceutical composition comprises a quick release oral formulation.
19. The method of claim 1 , wherein the pharmaceutical composition comprises a delayed release oral formulation.
20. The method of claim 1 , wherein the disease is excessive daytime sleepiness in a patient with Parkinson's disease.
21. The method of claim 1 , wherein the disease is chronic fatigue in a patient with Parkinson's disease.
22. A method of treating excessive daytime sleepiness in a patient with Parkinson's disease, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of Formula (IA):
or a pharmaceutically acceptable salt thereof, wherein,
each of R h and R f is hydrogen; and
R g is selected from hydrogen and C 1-3 alkyl.
23. The method of claim 22 , wherein the compound is 4-((L-valyl)oxy)butanoic acid (IIA) or a pharmaceutically acceptable salt thereof:
24. The method of claim 22 , wherein the compound is 4-(glycyloxy)buatanoic acid (IIB) or a pharmaceutically acceptable salt thereof:
25. The method of claim 22 , wherein the compound is 4-((L-alanyl)oxy)butanoic acid (IIC) or a pharmaceutically acceptable salt thereof:
26. A method of treating chronic fatigue in a patient with Parkinson's disease, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of Formula (IA):
or a pharmaceutically acceptable salt thereof, wherein,
each of R h and R f is hydrogen; and
R g is selected from hydrogen and C 1-3 alkyl.
27. The method of claim 26 , wherein the compound is 4-((L-valyl)oxy)butanoic acid (IIA) or a pharmaceutically acceptable salt thereof:
28. The method of claim 26 , wherein the compound is 4-(glycyloxy)buatanoic acid (IIB) or a pharmaceutically acceptable salt thereof:
29. The method of claim 26 , wherein the compound is 4-((L-alanyl)oxy)butanoic acid (IIC) or a pharmaceutically acceptable salt thereof: