Deuterated analogs of acetyl-leucine
The present disclosure provides compounds represented by Formula I: I, and the pharmaceutically acceptable salts and solvates thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , and R 13 are as defined as set forth in the specification, and the deuterium enrichment of any one or more of R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , and R 13 is about 15% or more. The present disclosure also provides compounds having Formula I for use to treat or delay the progression of a lysosomal storage disorder or a neurodegenerative disease in a subject, provide neuroprotection in a subject having a lysosomal disorder, treat or prevent a migraine, and the symptoms associated therewith, in a subject, or improve mobility and/or cognitive function in a subject.
1. A compound, or a pharmaceutically acceptable salt thereof, that is:
2. A compound, or a pharmaceutically acceptable salt thereof, that is:
3. A pharmaceutical composition comprising the compound of claim 1 or 2 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
4. A method of treating or delaying the progression of a lysosomal storage disorder, the method comprising administering to a subject in need thereof a therapeutically effective amount of the compound of claim 1 or 2 , or a pharmaceutically acceptable salt thereof.
5. The method of claim 4 , wherein the lysosomal storage disorder is Niemann-Pick Type C, Tay-Sachs disease, Sandhoff disease, GM1 gangliosidosis or Fabry disease.
6. The method of claim 5 , wherein the lysosomal storage disorder is Niemann-Pick Type C.
7. The method of claim 5 , wherein the lysosomal storage disorder is Tay-Sachs disease.
8. The method of claim 5 , wherein the lysosomal storage disorder is Sandhoff disease.
9. The method of claim 5 , wherein the lysosomal storage disorder is GM1 gangliosidosis.
10. The method of claim 5 , wherein the lysosomal storage disorder is Fabry disease.
11. A method of providing neuroprotection in a subject having a lysosomal storage disorder, the method comprising administering to a subject in need thereof a therapeutically effective amount of the compound of claim 1 or 2 , or a pharmaceutically acceptable salt thereof.
12. A method of treating or delaying the progression of a neurodegenerative disease, the method comprising administering to a subject in need thereof a therapeutically effective amount of the compound of claim 1 or 2 , or a pharmaceutically acceptable salt thereof.
13. A method of treating or preventing a migraine, and the symptoms associated therewith; improving mobility; improving cognitive function; treating or preventing restless legs syndrome, and the symptoms associated therewith; or treating or preventing vertigo, and the symptoms associated therewith, the method comprising administering to a subject in need thereof a therapeutically effective amount of the compound of claim 1 or 2 , or a pharmaceutically acceptable salt thereof.
14. The method of claim 13 for treating or preventing a migraine, and the symptoms associated therewith.
15. The method of claim 13 for improving mobility.
16. The method of claim 13 for improving cognitive function.
17. The method of claim 13 for treating or preventing restless legs syndrome, and the symptoms associated therewith.
18. The method of claim 13 for treating or preventing vertigo, and the symptoms associated therewith.
19. A kit comprising the compound of claim 1 or 2 , and instructions for administering the compound to a subject to treat or delay progression of a lysosomal storage disorder, treat or delay the progression of a neurodegenerative disease, treat or prevent a migraine, and the symptoms associated therewith, treat or prevent restless legs syndrome, and the symptoms associated therewith, treat or prevent vertigo, and the symptoms associated therewith, or improve mobility and cognitive function.
20. A kit comprising the compound of claim 1 or 2 , and instructions for administering the compound to provide neuroprotection in a subject having a lysosomal disorder.