Synthetic cannabinoids and nearness in pharmacophore to synthetic opioids.

[Nagelfar]

APP-FUBINACA

Seems fairly close in skeleton to the fentanyls:

I know most known cannabinoid *antagonists* are also opioid inverse agonists. Since opioid agonists & antagonists are so close in structure, a cannabinoid antagonist that is an opioid agonist would be an interesting one.

 

[roi]

Not really?

 

[serotonin2A]

I don't really see the similarity. Fairly close is not going to yield binding -- the moieties that interact with the receptor have to occupy the same 3D region of space.

Even with fentanyl, many times making simple changes to the structure yields ligands that are inactive even though they are "fairly close" in structure. For example, benzyl fentanyl (which I think is even more structurally similar to the cannabinoid pictured here vs fentanyl) is inactive. The same is true of the fentanyl analog where the position of the piperidine nitrogen is rotated by one methylene unit.

 

[Nagelfar]

I don't really see the similarity. Fairly close is not going to yield binding -- the moieties that interact with the receptor have to occupy the same 3D region of space.

Even with fentanyl, many times making simple changes to the structure yields ligands that are inactive even though they are "fairly close" in structure. For example, benzyl fentanyl (which I think is even more structurally similar to the cannabinoid pictured here vs fentanyl) is inactive. The same is true of the fentanyl analog where the position of the piperidine nitrogen is rotated by one methylene unit.

This I am aware, and thanks for the 3D on this 1 roi, what program is that? I need one that works online and overlays two or more like chemicalize does for 2D. Great divergences can yield similar and likewise small changes can be of an entirely other functionality, etc. etc. Still, I'm sure something's gotta overlay, say, Rimonabant that can be tool'd with to see what I'm getting @.

For instance:

Dimethylaminopivalophenone + Lefetamine reminds me quite a bit of Taranabant

 

[thizzkid]

YEa man as others have stated; this is quite the stretch of a comparison. Granted drugs are always more than they appear, but the only true similarity Im seeing here is the number of carbons between the benzene and center nitrogen in each of the compunds pictured in the OP. Even here, the amide group present in APP-FUBINACA and absent in the fentanyl structure is a MASSIVE difference.

Also, take a look at the fore mentioned, center nitrogen in each molecule; In APP-FUBINACA there is a "flat" (not really flat) structural composition whereas in fentanly this is cyclic yielding a much more 3D shape at least at that portion. From there the molecules are almost entirely different with the amino-alkyl base within APP-FUBINACA that is absent in fentanyls, etc. etc.

None of this necessarily takes away from your interesting speculation of hybrid inverse antagonist/agonist's as that point I cannot speak upon but it is valid and a curious point indeed.

However, I would possibly take a different intellectual approach to this comparison than simply their structure. That is me though and I am naive bluelighter so hey what do I know right? Cool post though I'd like to see what more people say in regards.