7,8-dihydoxyflavone and 7,8-substituted flavone derivatives, compositions, and methods related thereto
In certain embodiments, the disclosure relates to 7,8-dihydoxyflavone and 7,8-substituted flavone derivatives, such as those described by formula provided herein, pharmaceutical compositions, and methods related thereto. In certain embodiments, the disclosure relates to methods of treating or preventing diseases or conditions related to BDNF and TrkB activity, such as psychiatric disorders, depression, post-traumatic stress disorder, and autism spectrum disorders, stroke, Rett syndrome, Parkinson's disease, and Alzheimer's disease by administering effective amounts of pharmaceutical compositions comprising compounds disclosed herein to a subject in need thereof. In certain embodiments, it is contemplated that the 7,8-substituted flavone derivatives disclosed herein are prodrugs of 7,8-dihydoxyflavone and analogs.
1. A compound having Formula I:
or a salt thereof wherein
X is O;
U and Y are each O, NH, or Nalkyl;
Z is hydrogen;
R 1 is alkyl;
R 2 is alkyl; and
R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are each hydrogen.
2. The compound of claim 1 , wherein U and Y are NH or Nalkyl.
3. The compound of claim 1 , wherein U and Y are oxygen.
4. The compound of claim 1 , selected from:
diethyl (4-oxo-2-phenyl-4H-chromene-7,8-diyl) dicarbonate;
4-oxo-2-phenyl-4H-chromene-7,8-diyl bis(ethylcarbamate); and
4-oxo-2-phenyl-4H-chromene-7,8-diyl bis(dimethylcarbamate), or a salt thereof.
5. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable excipient.
6. The composition of claim 5 , wherein the pharmaceutical composition is in the form of a tablet, capsule, pill, or solution for injection.
7. The compound of claim 1 , wherein the compound is 4-oxo-2-phenyl-4H-chromene-7,8-diyl bis(methylcarbamate) or a salt thereof.
8. A compound selected from:
4-oxo-2-phenyl-4H-chromene-7,8-diyl dipropionate;
4-oxo-2-phenyl-4H-chromene-7,8-diyl bis(2,2-dimethylpropanoate); and
4-oxo-2-phenyl-4H-chromene-7,8-diylbis(3-methylbutanoate), or a salt thereof.