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piperazine-opioids

M

morphiquet

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Joined
Aug 6, 2005
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i came across a new family of opioids some time ago bearing a piperazine-ring in their structure, but i wasn't able to find anything about their potencies or half-lives.they can be distinguished into 3 major classes.
1. 1-(1,2-diphenylethyl)-piperazines
2. 1-cinnamyl-4-propionyl-piperazines
3. 1-((4-amidophenyl)-(phenyl)-methyl)-piperazines

has anyone ever made experiences with those compounds? i'd be very interested to read any information that is related to those compounds.
so don't hesitate to post :)
 
I could be wrong, but I thought the piperazine opiods were the chemical names for fentanyl analogues.
 
Fentanyl and derivatives are piperidines, not piperazines.

Amongst class #1 are apparently some potent opioids. There are some J. Med. Chem. papers on them. MT-45 also belongs to this class. 1-(2-Methoxyphenyl)-4-(2-(3-methoxyphenyl)-1-phenylethyl)piperazine is about 2x as potent as morphine, and demethylation gives compounds with very respectable potency.

Class #2 is represented by bucinnazine (1-butanoyl-4-cinnamyl piperazine, AP-237), but I doubt it's a real µ agonist. It shows cross-tolerance with morphine, but little dependence and withdrawals.

I know nothing of class #3, maybe you could post some more info?
 
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class 3 is derived from delta-opioid-agonists.
there are some with a diethyl-amido-group at the para-position of one phenyl-ring.

now recently it has been discovered, that you get to highly selective mu-agonists when one ethyl-substituent is metabolically (or by other methods) removed to give a monoethyl-amido-substituent.

do you have some further info on MT-45 ? that sounds quite interesting.
what do you exactly mean with "some potent opioids"?
twice morphine? 100x morphine?

ok thanx very much :)
 
Dr.Heckyll said:
Just do a pubmed search. Here's a reference for MT-45:
http://www.ncbi.nlm.nih.gov/entrez/...st_uids=962421&query_hl=8&itool=pubmed_docsum
Click to expand...

And if you put a meta-hydroxy on the phenyl ring the furthest from the aminogroup it gets much more potent.

Regarding the 1-cinnamyl-4-propionyl-piperazines there are versions that are bridged across the piperazine ring, which seems to be a couple times more potent than morphine. The most potent in the paper I have is active at 0.2mg/kg (= 10 times morphine they say). See J Med Chem 8: 331.
The proper name for that particular substance is 3-cinnamyl-8-propionyl-3,8-diazabicyclo[3.2.1]octane... nice and simple ;)
 
ralf2 said:
The proper name for that particular substance is 3-cinnamyl-8-propionyl-3,8-diazabicyclo[3.2.1]octane... nice and simple ;)
Click to expand...

The 3,9-diazabicyclo[3.3.1]nonane analogue is similar, and both have the drawback that the heterocycle is very much work to make. I'd look for soemthing simpler to make. The 1-(1,2-diphenylethane) piperazines are good targets with reasonable potency.
 
hey, dr. heckyll thanks for your pdf-compilation :)
although i already read most of these abstracts, i haven't read the one which mentions the derivative with the potency of 105.
do you know more about this compound and its substitution-patterns?

it's not very amazing that these 3-hydroxy-derivatives are the really potent ones as we find 3-hydroxys throughout the world of opioids.
that is, as far as i remember, also the case in the second class of compounds (1-cinnamyl-4-propionyl-piperazines).

btw dr.heckyll, i've got the strong notion that you know even more exotic opioids than myself does. so as i'm an enthuastic collector, would you mind to share them with me?
 
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The 105x morphine is, as you might have suspected, 1-(2-methoxyphenyl)-4-(2-(3-hydroxyphenyl)-1-phenylethyl)piperazine.
 
Im assuming that this is the correct structure:

piperazine.gif

Has anybody got a spare copy of the pdf or know where I can get one?
I had this article a few years ago but havent seen it since then.
 
Some but not all but a lot of piperazines have a tendency to block D2 receptors. Piperidines such as the fentanyl family are another story.
 
I had always thought that para-hydroxy lefetamine analogues would be the more reasonable choices, but that doesn't seem to be true. the meta hydroxy piperazine derivatives are quite potent.
 
My concern would be non-opioid properties of these drugs, or non-MOR opioid affinities....

There are better prospects....

Like the numerous 4-aminocyclohexanol substituents, such as Bromadol

220px-Bromadol.png


10,000x morphine in potency, highly MOR specific, and not especially difficult to synthesize. I believe it can be made with 1,4-dioxocyclohexane, which is easy to obtain. Plus, all of these substituted 4-aminocyclohexanol opioids are legal....
 
I have some recent experiences with Bucinnazine (AP-237). It is an overall pleasant compound, but definitely different from the other opioid compounds that I know. It feels like it also has some dissociative properties, not per se like ketamine (or any of the other better known dissociatives), but in it's own way. Don't have anything to compare it with, maybe in a slightly similar way as pentazocine also does, but still not quite the same.

My normal dose for this compound is between 100-200mg, that is for someone with little to none tolerance to opioids. At the 200mg dose, it felt it was starting to produce some unwanted side effects. I presume because of the 'dirty' pharmacological profile of the compound. Although the latter is just an assumption, based on the chemical structure of this compound.
I found these papers, but couldn't get excess, but perhaps they will tell a little more about the profile of the compound;
- http://www.ncbi.nlm.nih.gov/pubmed/1156016
- http://www.ncbi.nlm.nih.gov/pubmed/1156018

The come-up is pretty fast, ~20min for me on an empty stomach. The total effects last about 5-6 hours, but the opioid effects wear off after 2-3 hours.

All in all, a quit nice compound, but people searching for a proper opioid replacement will probably be disappointed.
 
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