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4-anilidopiperidine SAR data?

Pharaoh Sphinx

Pharaoh Sphinx

Ex-Bluelighter
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May 23, 2006
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Theoretically speaking, aside from methyl additions, beta-hydroxy additions, and swappin for thio-fent, are there any other fairly predictable ADDITIONS that can be made anywhere to the structure assuming the aforementioned variables are ALL in place??

As well has anyone heard of the 'o-fluoro'?? not to be confused with the 'p-fluoro' which diminishes potency.
 
Pharaoh Sphinx said:
Theoretically speaking, aside from methyl additions, beta-hydroxy additions, and swappin for thio-fent, are there any other fairly predictable ADDITIONS that can be made anywhere to the structure assuming the aforementioned variables are ALL in place??

As well has anyone heard of the 'o-fluoro'?? not to be confused with the 'p-fluoro' which diminishes potency.
Click to expand...

eh?
not really sure what the question is..are you saying hypothetically all these substitutions are already there? which doesn't make a lot of sense.

I am assuming that taking the fent structure as a basis what modifications have been added whilst keeping the efficacy as a mu agonist?

there are a huge list of modifications that work the opioid receptor is very tolerant of modifications to lead compounds, probably beacuse the endogenous ligand is relatively large.) substitution at the 4 position, alkylcarbonyl and alkoxycarbonyl as well as alkyl and alkenyl at the 3 position of the piperdine.. putting in a 2 carbon bridge to make a tropane retains activity then so does opening the piperidine ring to get the seco compound. the phenyl in the phenethyl group has been replaced with an ester to make the 'soft' fentanyls I could go on and on the list is endless. I suggest a patent search.

I still don't get the obsession with potency. if something is ten times more potent but still as toxic as the lead compound then that is a good thing.
If something is ten times more potent AND ten times more toxic then thats ten times the fuck up factor.
 
http://opioids.com/ohmefentanyl/fluorohmf.pdf

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Sorry to bring up such an old topic but I've seen only one mention of replacement of the phenethyl of fentanyl with a methyl. If theres any analogy to demerol, then it should diminish potency, and for some reason I'm thinking increase duration of activity? How about a formanilide compound? I think I've read that such compounds are actually more potent than the acetanilide analogs, but I am very uninformed as to what sort of pharmacological impacts such modifications may cause. E.g. fentanyl known being an NMDA agonist, and other non-opioid actions that many opioids have.
 
not forgetting that the phenylethyl or heteroarylethyl can be replaced with carboxylic acid esters or tetrazoles or other such wierdness.
 
The position of the sulphur in the thienyl ring IS important (or at least it was in the phenyl piperidine analog series. The UK laws have some analog rules so most fentanyls are covered. The only one I can think of that would escape would be using either a 7 membered ring or using a bridge like fencamfamine (nbomananone)
I realize that isomers have to be seperated, but this would produce a strong opioid that is outside the MoDA...
 
The N-methyl is not effective. You need a 2 carbon spacer then something on the end. This can be a benzene,2-thienyl, or tetrazole (presumably others will have some activity) or even a simple ester (remifentanil).
Methyl is the optimal piperidine substituant. Beta hydroxy is the optimal for the ethyl spacer and 4-fluoro benzene is the optimal at the end of the ethyl chain.

I have to say, after all the research done on the fentanyl class of opioid, I very much doubt that it can be made more potent than p-F ohmefentanyl. Of course, only 1 of the 8 isomers is that strong. That's the beauty of bromidol, only 2 isomers.
 
can anyone confer the claim of the deleted thread starter that p-fluoro-anilide diminishes potency? i believe that i read somewhere one day that this analogue is quite equal to fentanyl.

also interesting are the substitutions for the propionyl-moiety such as 2-furanylcarbonyl (mirfentanil) or methoxyacetyl (brifentanil). how do these influence potency, don't know of any studies. so if someone could guide me to one, that'd be nice :)

@vector: it's not true that secofentanyl would retain potency, it's in fact 50 times less strong than fentanyl.
 
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