aced126
Bluelighter
- Joined
- May 18, 2015
- Messages
- 1,047

Ketone should still provide some (although probably a lot less than carbomethoxy counterpart) interaction with tyrosine-156? Could be a more mixed reuptake inhibitor/releasing agent? Longer half life as well as higher oral bioavailability as the ester bond previously is replaced by a C-C bond preventing hydrolysis.
Maybe probe the binding pocket more with carbons in hopes of blocking the conformational change when DAT tries to transport this molecule into the neuron. Should give more reuptake and less releasing character to the molecule as well as increase BBB penetration.




Maybe a charged nitrogen in place of the ketone could do even better at binding to Y156.

How about locking it into 1 of the following conformations for increased (or decreased) selectivity?



Secondary amines should have maximum basicity as well so gets charged easily.
I expect the last 2 to perform reuptake the best due to the distance between the non-amphetaminergic amine and the ring (tyr residue likely to be close to the ring).
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