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 and other forms of retinal disease mediated by accumulation of A2E and/or lipofuscin in a subject, the method comprising administering to the subject in need thereof a composition comprising a compound of formula IIIa:
or a pharmaceutically acceptable salt thereof, wherein:
A is;
B is a halogen atom, hydroxyl, carbamoyl, aryl or amino;
p is 0, 1, 2, or 3;
D is unbranched lower alkyl;
L is a single bond or CH 2 ; and
X, Y, and Z are each, independently, N, NH, O, S, CB, CH, or absent, such that at least one of X, Y, and Z is N or NH; wherein X, Y, and Z and the carbon atoms to which they are attached form a 5- or 6-membered optionally substituted heterocyclic ring.
2. The method of claim 1 , wherein
one of X or Z is N and the remaining X or Z is O;
Y is absent; such that X and Z and the carbon atoms to which they are attached form a 5-membered heterocyclic ring; and
p is 1.
3. The method of claim 2 , wherein L is a single bond.
4. The method of claim 3 , wherein X is O and Z is N.
5. The method of claim 3 , wherein X is N and Z is O.
6. The method of claim 4 , wherein B is aryl.
7. The method of claim 5 , wherein B is aryl.
8. The method of claim 6 , wherein B is phenyl.
9. The method of claim 7 , wherein B is phenyl.
10. The method of claim 3 , wherein D is CH 3 .
11. The method of claim 10 , wherein the compound is
or pharmaceutically acceptable salts thereof.
12. The method of claim 11 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
13. The method of claim 11 , wherein the compound is
or a pharmaceutically acceptable salt thereof.