Compositions and methods of treating retinal disease
Compositions and methods for treating macular degeneration and other forms of retinal disease whose etiology involves the accumulation of A2E and/or lipofuscin, and, more specifically, for preventing the formation and/or accumulation of A2E are disclosed.
1. A method of treating macular degeneration or a retinal disease mediated by the accumulation of N-retinylidene-N-retinylethanolamine (A2E) and/or lipofuscin, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I):
or a pharmaceutically acceptable salt thereof,
wherein
W, X, Y, and Z are each independently N, S, O, CU, CH, or C with the —NH 2 , wherein at least one of W, X, Y and Z is N;
A is selected from the group consisting of
wherein
D is an unbranched C 1-6 alkyl, wherein each D can be the same or different; and
R is a substituted or unsubstituted C 1-8 straight chain alkyl or C 3-8 branched chain alkyl;
U is selected from halogen, cyano, lower alkyl, and aryl, wherein one or more hydrogen atoms on the lower alkyl or aryl are optionally substituted by substituents selected from the group consisting of halogen, hydroxyl, carbamoyl, amino and aryl, and
n is 0, 1, 2, 3, or 4.
2. The method of claim 1 , wherein A is
wherein D is an unbranched C 1-6 straight chain alkyl.
3. The method of claim 2 , wherein each D is methyl.
4. The method of claim 1 , wherein n is 0 or 1.
5. The method of claim 1 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
6. The method of claim 1 , where the compound is
7. The method of claim 1 , wherein the macular degeneration is age-related macular degeneration (AMD).
8. The method of claim 7 , wherein the AMD is wet AMD or dry AMD.
9. The method of claim 1 , wherein the macular degeneration is Stargardt's disease.
10. The method of claim 1 , wherein U is a halogen.
11. The method of claim 10 , wherein the halogen is chloro or bromo.