Overlay Fentanyl (x80 M), 4-phenyl Phenapromide (x60 M) & N-phenylethyl Dimethylaminopivalophenone (With a look at Diampromide)

[4DQSAR]

After disappointing in vivo testing with multiple people and some unfortunately easy google searches, I'm confident dimethylaminopivalophenone and carl's pyrrolidino analogue are NOT opioids.

Well, the former overlays 3,3-dimethylprodine.

The Thorpe-Ingold effect (also known as the gem-dimethyl ring closure) means that the aromatic, oxygen*, the 3-disubstitution, nitrogen and importantly the lone-pair of that nitrogen all overlay.

Sci-Hub. Racemic and optically active 1,3,3-trimethyl-4-phenyl-4-(propionyloxy)piperidine / Journal of Medicinal Chemistry, 1985

It's an odd one because one of the two N-methyls overlays the N-methyl of 3,3-dimethyl prodine BUT the other bends back as part of the ring-closure.

BUT it IS flexible, the conformation being dependent on THAT conformation being the lowest energy conformation. Which is why I presumed it's potency is an order of magnitude lower than 3,3-dimethylprodine.

I assume you followed the synthesis as described in that original paper but have you checked the conformation of the product? I would be interested to see the GC-MS/NMR data. If nothing else, an MP test is going to tell you if the product is a mixture.

Don't forget, what was measured in animal models was the analgesic activity. It's almost impossible to even estimate what the subjective effects will be. Hey, if it's an analgesic which produces no other subjective effects, that would actually be a positive! But the MOST one could reasonably expect would be that it would serve as an active cut, a dubious path at best. But if you have experienced pethidine, you will appreciate that the only people who (apparently) like the stuff are the ones to absolutely do stray beyond that TI.

I used to know a guy nicknamed 'Digshit Jim' who had a pin fixation and would sit there banging up pill after pill after pill. I don't think we ever worked out exactly what produced that compulaion but for whatever reasons, he couldn't get enough of the stuff.

I don't recall how the TI was calculated, let alone what toxic effects were demonstrated but IF it's similar to pethidine, it's actually norpethidine that's the issue.

*Don't forget that similarly, the Utopioids have a C=O as their benzylic carbons. I can find other examples of opioids in which the benzylic carbon is a ketone. It isn't unique by any means.