Pyrazolopyridazines and methods for treating retinal-degenerative diseases and hearing loss associated with usher syndrome
Compounds, compositions and methods for the treatment of retinal degenerative diseases, such as retinitis pigmentosa, Leber's congenital Amaurosis, Syndromic retinal degenerations, age-related macular degeneration and Usher Syndrome, and hearing loss associated with Usher Syndrome are described herein.
1. A compound having the structure:
or a pharmaceutically acceptable salt thereof.
2. A composition comprising an effective amount of a compound or pharmaceutically acceptable salt of the compound of claim 1 and a pharmaceutically acceptable carrier or vehicle.
3. A method for treating a retinal degenerative disease, comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt of the compound of claim 1 .
4. The method of claim 3 , wherein the retinal degenerative disease is retinitis pigmentosa, Leber's congenital Amaurosis, a syndromic retinal degeneration, age-related macular degeneration or Usher Syndrome.
5. A method for treating retinitis pigmentosa, Leber's congenial Amaurosis, syndromic retinal degeneration, age-related macular degeneration or Usher Syndrome, comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt of the compound of Formula I, Formula II, Formula III, Formula XIII, Formula XIV or Formula XV;
wherein Formula I has the structure:
wherein R 1 is:
R 2 is:
and a is 0, 1, or 2;
wherein Formula II has the structure:
wherein R 3 is:
b is 0 or 1; and
c is 1 or 2;
wherein Formula III has the structure:
wherein R 4 is
wherein Formula XIII has the structure:
wherein R 5 is:
R 6 is:
and
a is 0, 1, or 2;
wherein Formula XIV has the structure:
wherein R 7 is:
b is 0 or 1; and
c is 1 or 2; and
wherein Formula XV has the structure:
wherein R 8 is:
6. The method of claim 5 , wherein the Usher syndrome is Usher I Syndrome, Usher II Syndrome, or Usher III Syndrome.
7. The method of claim 5 , wherein the Usher syndrome is Usher III syndrome.
8. A method for treating retinitis pigmentosa, Leber's congenital oAmaurosis, syndromic retinal degeneration, age-related macular degeneration or Usher Syndrome, comprising administering to a subject in need thereof an effective amount of a compound having the structure:
or a pharmaceutically acceptable salt thereof, or XIIIa:
9. The method of claim 8 , wherein the Usher syndrome is Usher I Syndrome, Usher II Syndrome, or Usher III Syndrome.
10. The method of claim 8 , wherein the Usher syndrome is Usher III syndrome.
11. The method of claim 4 , wherein the retinal degenerative disease is Usher Syndrome.
12. A method for treating hearing loss associated with Usher syndrome, comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt of the compound of claim 1 .
13. The method of claim 12 , wherein the Usher syndrome is Usher I Syndrome, Usher II Syndrome, or Usher III Syndrome.
14. The method of claim 12 , wherein the Usher syndrome is Usher III syndrome.
15. The method of claim 11 , wherein the Usher syndrome is Usher I Syndrome, Usher II Syndrome, or Usher III Syndrome.
16. The method of claim 11 , wherein the Usher syndrome is Usher III syndrome.