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 of formula:
or a pharmaceutically acceptable salt thereof
wherein,
X is CH;
Y is C with the —NH 2 attached to Y;
Z is N;
A is
and
D is a 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, C7or 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 A is:
3. The compound of claim 1 which is:
or a pharmaceutically acceptable salt thereof.
4. A pharmaceutical composition comprising a compound of formula:
or a pharmaceutically acceptable salt thereof
wherein,
X, Y, and Z are each, independently, N, CH, or C with the —NH 2 attached, wherein at least one of X, Y and Z is N;
A is
D is a unbranched lower alkyl;
R is substituted or unsubstituted C1, C2, C3, C4, C5, C6, C7, or C 8 straight chain alkyl, or substituted or unsubstituted C3, C4, C5, C6, C7or 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; and
a pharmaceutically acceptable carrier.
5. The pharmaceutical composition of claim 4 , wherein
X is CH;
Y is C with the —NH 2 attached to Y; and
Z is N.
6. The pharmaceutical composition of claim 4 , wherein A is:
7. The pharmaceutical composition of claim 6 , wherein each D is methyl.
8. The pharmaceutical composition of claim 4 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
9. The pharmaceutical composition of claim 5 , wherein A is: