TrkB agonists and methods of use
Compounds and methods related to the activation of the TrkB receptor are provided. The methods include administering a 7,8-dihydroxyflavone derivative with modified flavone or heterocyclic ring to a subject in need thereof. Methods and compounds for the treatment of disorders including neurologic disorders, neuropsychiatric disorders, and metabolic disorders (e.g., obesity) are provided.
1. A method of treating of treating depression comprising administering, to a subject in need thereof, an effective amount of a compound Formula F,
or salts or prodrugs thereof wherein,
X is hydrogen, dialkylamino, or heterocyclyl, wherein X is optionally substituted with one or more, the same or different R 8 ;
R 2 is hydrogen, alkoxy, hydroxy, or alkanoyloxy, wherein R 2 is optionally substituted with one or more, the same or different R 8 ;
R 3 is hydrogen, alkoxy, hydroxy, dialkylamino, or alkanoyloxy, wherein R 3 is optionally substituted with one or more, the same or different R 8 ;
R 4 is hydrogen or halogen;
R 5 is hydrogen, alkoxy, hydroxy, or alkanoyloxy wherein R 5 is optionally substituted with one or more, the same or different R 8 ; and
R 8 is alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, (alkyl) 2 amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R 8 is optionally substituted with one or more, the same or different, R 9 ;
R 9 is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N-ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl; and
R 10 and R 11 are each, the same or different hydrogen, alkyl, or alkanoyl.
2. The method of claim 1 , wherein the compound is selected from:
8-(4-(dimethylamino)phenyl)chromeno[7,8-d]imidazol-6(3H)-one and
8-(4-(dimethylamino)phenyl)-7-fluorochromeno[7,8-d]imidazol-6(3H)-one, or salts thereof.
3. The method of claim 1 , wherein the composition is administered in combination with an antidepressant.