Compounds and methods of treating retinal degeneration
A method of treating retinal degeneration in a subject includes administering to the subject a therapeutically effective amount of a compound of formula (I).
1. A pharmaceutical composition for treating retinal degeneration in a subject, the composition comprising a compound having formula (I);
wherein X 1 is CH 2 , C═O, or N—R 3 ;
wherein X 2 is O or N—R 4 ;
wherein at least one of X 1 is not N—R 3 or X 2 is not N—R 4 ;
wherein R 1 and R 2 are each independently selected from the group consisting of hydrogen, a substituted or unsubstituted cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein at least one of R 1 or R 2 is a substituted or unsubstituted thiophene;
wherein R 3 and R 4 are each independently selected from the group consisting of hydrogen, a substituted or unsubstituted C 1 -C 24 alkyl, C 2 -C 24 alkenyl, C 2 -C 24 alkynyl, C 3 -C 20 aryl, heteroaryl, heterocycloalkenyl containing from 5-6 ring atoms (wherein from 1-3 of the ring atoms is independently selected from N, NH, N(C 1 -C 6 alkyl), NC(O)(C 1 -C 6 alkyl), O, and S), C 6 -C 24 alkaryl, C 6 -C 24 aralkyl, halo, —Si(C 1 -C 3 alkyl) 3 , hydroxyl, sulfhydryl, C 1 -C 24 alkoxy, C 2 -C 24 alkenyloxy, C 2 -C 24 alkynyloxy, C 5 -C 20 aryloxy, acyl, acyloxy, C 2 -C 24 alkoxycarbonyl, C 6 -C 20 aryloxycarbonyl, C 2 -C 24 alkylcarbonato, C 6 -C 20 arylcarbonato, carboxy, carboxylato, carbamoyl, C 1 -C 24 alkyl-carbamoyl, arylcarbamoyl, thiocarbamoyl, carbamido, cyano, isocyano, cyanato, isocyanato, isothiocyanato, azido, formyl, thioformyl, amino, C 1 -C 24 alkyl amino, C 5 -C 20 aryl amino, C 2 -C 24 alkylamido, C 6 -C 20 arylamido, imino, alkylimino, arylimino, nitro, nitroso, sulfo, sulfonato, C 1 -C 24 alkylsulfanyl, arylsulfanyl, C 1 -C 24 alkylsulfinyl, C 5 -C 20 arylsulfinyl, C 1 -C 24 alkylsulfonyl, C 5 -C 20 arylsulfonyl, phosphono, phosphonato, phosphinato, phospho, or phosphino or combinations thereof;
and pharmaceutically acceptable salts thereof.
2. A pharmaceutical composition for treating retinal degeneration in a subject, the composition comprising a compound having formula (III):
wherein R 2 and R 6 are each individually hydrogen, a substituted or unsubstituted C 1 -C 24 alkyl, C 2 -C 24 alkenyl, C 2 -C 24 alkynyl, C 3 -C 20 aryl, heteroaryl, heterocycloalkenyl containing from 5-6 ring atoms (wherein from 1-3 of the ring atoms is independently selected from N, NH, N(C 1 -C 6 alkyl), NC(O)(C 1 -C 6 alkyl), O, and S), C 6 -C 24 alkaryl, C 6 -C 24 aralkyl, halo, —Si(C 1 -C 3 alkyl) 3 , hydroxyl, sulfhydryl, C 1 -C 24 alkoxy, C 2 -C 24 alkenyloxy, C 2 -C 24 alkynyloxy, C 5 -C 20 aryloxy, acyl, acyloxy, C 2 -C 24 alkoxycarbonyl, C 6 -C 20 aryloxycarbonyl, C 2 -C 24 alkylcarbonato, C 6 -C 20 arylcarbonato, carboxy, carboxylato, carbamoyl, C 1 -C 24 alkyl-carbamoyl, arylcarbamoyl, thiocarbamoyl, carbamido, cyano, isocyano, cyanato, isocyanato, isothiocyanato, azido, formyl, thioformyl, amino, C 1 -C 24 alkyl amino, C 5 -C 20 aryl amino, C 2 -C 24 alkylamido, C 6 -C 20 arylamido, imino, alkylimino, arylimino, nitro, nitroso, sulfo, sulfonato, C 1 -C 24 alkylsulfanyl, arylsulfanyl, C 1 -C 24 alkylsulfinyl, C 5 -C 20 arylsulfinyl, C 1 -C 24 alkylsulfonyl, C 5 -C 20 arylsulfonyl, phosphono, phosphonato, phosphinato, phospho, or phosphino or combinations thereof;
and pharmaceutically acceptable salts thereof.
3. A pharmaceutical composition for treating retinal degeneration in a subject, the composition comprising a compound having formula (IV):
wherein R 1 and R 7 are each individually hydrogen, a substituted or unsubstituted C 1 -C 24 alkyl, C 2 -C 24 alkenyl, C 2 -C 24 alkynyl, C 3 -C 20 aryl, heteroaryl, heterocycloalkenyl containing from 5-6 ring atoms (wherein from 1-3 of the ring atoms is independently selected from N, NH, N(C 1 -C 6 alkyl), NC(O)(C 1 -C 6 alkyl), O, and S), C 6 -C 24 alkaryl, C 6 -C 24 aralkyl, halo, —Si(C 1 -C 3 alkyl) 3 , hydroxyl, sulfhydryl, C 1 -C 24 alkoxy, C 2 -C 24 alkenyloxy, C 2 -C 24 alkynyloxy, C 5 -C 20 aryloxy, acyl, acyloxy, C 2 -C 24 alkoxycarbonyl, C 6 -C 20 aryloxycarbonyl, C 2 -C 24 alkylcarbonato, C 6 -C 20 arylcarbonato, carboxy, carboxylato, carbamoyl, C 1 -C 24 alkyl-carbamoyl, arylcarbamoyl, thiocarbamoyl, carbamido, cyano, isocyano, cyanato, isocyanato, isothiocyanato, azido, formyl, thioformyl, amino, C 1 -C 24 alkyl amino, C 5 -C 20 aryl amino, C 2 -C 24 alkylamido, C 6 -C 20 arylamido, imino, alkylimino, arylimino, nitro, nitroso, sulfo, sulfonato, C 1 -C 24 alkylsulfanyl, arylsulfanyl, C 1 -C 24 alkylsulfinyl, C 5 -C 20 arylsulfinyl, C 1 -C 24 alkylsulfonyl, C 5 -C 20 arylsulfonyl, phosphono, phosphonato, phosphinato, phospho, or phosphino or combinations thereof;
and pharmaceutically acceptable salts thereof.
4. The composition of claim 1 , wherein R 3 and R 4 are each independently selected from the group consisting of hydrogen, a substituted or unsubstituted C 1 -C 24 alkyl, a substituted or unsubstituted cycloalkyl, hetercyclyl, aryl, and heteroaryl.
5. The pharmaceutical composition of claim 1 , wherein the compound is selected from the group consisting of:
and
pharmaceutically acceptable salts thereof.
6. The composition of claim 1 , wherein the composition is formulated for at least one of topical administration, systemic administration, intravitreal injection, or intraocular delivery.