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 compound represented by the formula Ia:
or a pharmaceutically acceptable salt of Ia,
wherein
X is CH;
Z is N;
Y is C with the —NH 2 attached to Y;
p is 1, 2, or 3;
B is a halogen atom, hydroxyl, carbamoyl, substituted or unsubstituted aryl or amino wherein substituted aryl has one or more substituents selected from halogen, hydroxyl, alkoxy, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, alkylaminocarbonyl, aralkylaminocarbonyl, alkenylaminocarbonyl, arylcarbonyl, aralkylcarbonyl, alkenylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylthiocarbonyl, phosphate, phosphonato, phosphinato, cyano, amino, alkylamino, dialkylamino, arylamino, diarylamino, alkylarylamino, acylamino, alkylcarbonylamino, arylcarbonylamino, carbamoyl, ureido, amidino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, alkylsulfinyl, sulfamoyl, sulfonamido, nitro, trifluoromethyl, azido, heterocyclyl, alkylaryl, an aromatic moiety and a heteroaromatic moiety;
A is
D is unbranched lower alkyl; and
R is substituted or unsubstituted C1, C2, C3, C4, C5, C6, C7, or C8 straight chain alkyl, or substituted or unsubstituted C3, C4, C5, C6, C7 or C8 branched chain alkyl wherein said substituted straight chain alkyl or said substituted branched chain alkyl has one or more substituents selected from alkyl, alkenyl, alkynyl, halogen, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylthiocarbonyl, alkoxyl, phosphate, phosphonato, phosphinato, cyano, amino, alkylamino, dialkylamino, arylamino, diarylamino, alkylarylamino, acylamino, alkylcarbonylamino, arylcarbonylamino, carbamoyl, ureido, amidino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, alkylsulfinyl, sulfamoyl, sulfonamido, trifluoromethyl, azido, heterocyclyl, alkylaryl, an aromatic moiety and a heteroaromatic moiety.
2. The compound of claim 1 , wherein p is 1.
3. The compound of claim 2 , wherein A is
4. The compound of claim 3 , wherein D is CH 3 .
5. The compound of claim 4 , wherein B is a halogen atom.
6. A pharmaceutical composition, comprising the compound of claim 1
or a pharmaceutically acceptable salt thereof
and a pharmaceutically acceptable carrier.