Of course I understand that the D2/3/4 dopamine targeting is not the same as the dopamine active transporter / synaptic vesicular transport — it’s not a PURE mu/DAT ligand, yet, but I’ve only been working on it for 24 hours … if I discovered the right compound I’d be patenting it rather than using it to try and win an argument on some Internet forum.
I have studied the quantitative structure activity for opioids, and have found that, in morphinons, the tertiary amine when substituted with a n-phenethyl moiety is not an antagonist but rather an agonist (unlike n-methylcyclopropyl or n-methyvinyl) with increased potency and tighter binding affinity
Anything else?
Make it, Taste it or test it. In reality that is the only way to find out.
Then hang some more stuff off it to reduce the number of off target interactions whilst retaining the desired profile. I would guess as it stands there will be some interesting off target interactions with the drawn structure, This could easily keep someone busy for a while. the structure is pretty easy to make and play with. I wish you luck, if you get it right then you might discover something that is safer, better, shinier, cheaper whatever.
I doubt your drawn compound has not already been made and assayed, it is pretty obvious, a quick search turned up a couple of hits,
where simple 3 phenylpiperidine opioids are discussed, N-methyls are weak analgesics but it appears the N- phenethyl derivatives are active and not as antagonists in the example series. this paper also suggests that 3-hydroxy on the phenyl ring is needed for any activity whether agonist or antagonist.
https://doi.org/10.1002/jcc.540070414 on sci hub.
the N- phenethyl derivatives have significant activity in the range of meperidine (ref 11). N-phenethyl substituents also consistently increase activity optimally in rigid phenyl-axial compounds in the morphine, morphinan, and 6,7-benzomorphan classes of opioids
Ref (11) M.A. Iorio and A. F. Casy, J. Pharm. Pharmacol.,27, 140 (1975).
I haven't go the time to get the Ionio and Casy paper and read it but it probably contains answers, that or ref 16 which unfortunately is not copied on the sci hub version of the the paper.
Swiss target prediction is not really very reliable. Actually it is really bad. It is ok as a starting point but that is about it.
You are correct about the N-phenylethyl in mu agonists sometimes N-cinnamyl works too, though that is quite general there are plenty of exceptions. Mu is pretty tolerant of structure, the large size of the natural ligand leaves lots of space for smaller molecules to take a pose in the binding pocket and still activate the receptor.
I'm sure tapered-fertile-haribo-piglet will share his opinion, though there is an old saying regarding opinions being like assholes.....