It will be very similar to MXE. The QSAR is detailed in the EJoMC article I referenced. Of course, their are 4 enantiomers and I think only 1 is active. Of course, the LogP will be improved so maybe it's twice as active? Still, that still leaves 3 unwanted compounds that may have SOME effect.
The problem is that all of the arylcyclohexylamine derivatives are controlled.
That is why simply substituting a 4 thione for the cyclohexyl moiety is the most appropriate - it allows one to retrace the substitution patterns used in all of those novel RCs thus far marketed.
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Now, the APPROPRIATE analogue with a 2-thiophene aromatic and N-ethyl amine has sub nM affinity for the NMDA receptor but I always have to remind people that what K and all of the popular RC agents have NMDA antagonist, mu agonist & DRI activity. It's finding the balance that is key. Something that is just a highly potent NMDA antagonist may well have a market, but it wouldn't be as 'good' as MXE.
As far as I can see, swapping the cyclohexyl for a 4-thiane is going to be the most likely to directly substitute. Yes, the 4-thianes had more NMDA activity than the cyclohexyls but it wasn't an order of magnitude, it was about 10% if memory serves.
Of course, the chemistry behind such a substitution is interesting. But that is always the case. People are keen to name ligands with no way of making them which isn't practical.
