Prodrugs of gamma-hydroxybutyric acid, compositions and uses thereof
Provided are prodrugs of gamma-hydroxybutyric acid as well as compositions and uses thereof.
1. A compound having the structure of Formula (1D):
or a pharmaceutically acceptable salt thereof, wherein,
R 2 is —(CR 6 R 7 ) m —, wherein,
m is an integer from 1 to 6; and
each of R 6 and R 7 is independently selected from hydrogen and C 1-3 alkyl; and
R 3 is selected from C 5-8 aryl, C 3-8 heterocycloalkyl, C 5-8 heteroaryl, substituted C 1-12 alkyl, substituted C 5-8 aryl, substituted C 3-8 heterocycloalkyl, and substituted C 5-8 heteroaryl, wherein each of the one or more substituent groups is independently selected from halogen, C 1-6 alkyl, C 1-6 alkoxy, and —NR 2 , wherein each R is independently selected from hydrogen, C 1-6 alkyl, and C 1-6 alkylcarbonyl.
2. The compound of claim 1 , wherein each of R 6 and R 7 is hydrogen.
3. The compound of claim 1 , wherein R 2 is —(CH 2 ) 3 —.
4. The compound of claim 1 , wherein R 3 is substituted C 1-12 alkyl.
5. The compound of claim 1 , wherein R 3 is amino-substituted C 1-12 alkyl.
6. The compound of claim 1 , wherein R 3 is amino-substituted C 5 alkyl.
7. The compound of claim 1 , wherein,
R 2 is —(CH 2 ) 3 —; and
R 3 is amino-substituted C 5 alkyl.
8. A pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof.
9. The pharmaceutical composition of claim 8 , wherein the pharmaceutical composition comprises a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof for treating a disease in a patient, wherein the disease is selected from narcolepsy, cataplexy, excessive daytime sleepiness, fibromyalgia, chronic fatigue, and tardive dyskinesia.
10. The pharmaceutical composition of claim 8 , wherein the pharmaceutical composition is an oral formulation.
11. The pharmaceutical composition of claim 8 , wherein the pharmaceutical composition comprises a sustained release oral formulation.
12. The pharmaceutical composition of claim 8 , wherein the pharmaceutical composition comprises a delayed release oral formulation.
13. The pharmaceutical composition of claim 8 , wherein the pharmaceutical composition comprises a quick release oral formulation.
14. The pharmaceutical composition of claim 8 , wherein the pharmaceutical composition comprises an oral dosage form.
15. A method of treating a disease in a patient comprising administering to a patient in need of such treatment a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof to the patient, wherein the disease is selected from narcolepsy, cataplexy, excessive daytime sleepiness, fibromyalgia, chronic fatigue, and tardive dyskinesia.
16. The method of claim 15 , wherein the disease is cataplexy associated with narcolepsy.
17. The method of claim 15 , wherein the disease is excessive daytime sleepiness associated with narcolepsy.
18. The method of claim 15 , wherein the disease is excessive daytime sleepiness in a patient with Parkinson's disease.
19. The method of claim 15 , wherein the disease is chronic fatigue in a patient with Parkinson's disease.
20. The method of claim 15 , wherein administering comprises orally administering.
21. A method of treating a disease in a patient comprising administering to a patient in need of such treatment a therapeutically effective amount of the pharmaceutical composition of claim 8 to the patient, wherein the disease is selected from narcolepsy, cataplexy, excessive daytime sleepiness, fibromyalgia, chronic fatigue, and tardive dyskinesia.
22. The method of claim 21 , wherein the disease is cataplexy associated with narcolepsy.
23. The method of claim 21 , wherein the disease is excessive daytime sleepiness associated with narcolepsy.
24. The method of claim 21 , wherein the disease is excessive daytime sleepiness in a patient with Parkinson's disease.
25. The method of claim 21 , wherein the disease is chronic fatigue in a patient with Parkinson's disease.
26. The method of claim 21 , wherein administering comprises orally administering.