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Piperazines' SAR?

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Pomzazed

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Jun 10, 2007
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Has there been studies regarding psychoactive piperazine structure-activity relationship? As main (psychoactive) piperazines in the market can be classified to two groups:
- Phenylpiperazines
  • 1-phenylpiperazine : Has a report on erowid on misconception as BZP
  • 1-(3-chlorophenyl)piperazine : mCPP
  • 1-(3-trifluoromethylphenyl)piperazine : TMFPP
  • 1-(4-methoxyphenyl)piperazine : MeOPP
- Benzylpiperazines
  • 1-benzylpiperazine : BZP
  • 1-benzyl-4-methylpiperazine : reported to be more mellow to BZP
  • 1-(4-bromo-2,5-dimethoxybenzyl)piperazine : (found to be inactive)
  • 1-(benzo[1,3]dioxol-5-ylmethyl)piperazine : MDBZP - only have negative impact reports

So, what is known is that phenethylamine SAR is irrevalent to piperazine's, as report keeps coming. but what about...
  • Chain length : phenyl -> benzyl -> phenethyl -> phenylpropyl? benzylpiperazines seems to be more stimulating than phenylpiperazines. What about phenethyl? or would phenylpropyl possess (some) opioid activity?
  • Aromatic ring: is that important comparing to if it is some bulky alkyl groups, cyclics or long chain ones? (in the same fashion as amphet,propylhexedrine,dimethylamylamine)
  • Substituents : including both at the PP ring and the attached group

Any information on this?
 
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1-Naphtylpiperazine is a 5-HT1 agonist and a 5-HT2 antagonist,then theres Quipazine etc..I think we haven't found the "good" one yet in terms of acceptability...
 
what about dissociatives?

If i remember, a few piperazines are potent NMDA antagonists
 
^
thx dj, though i've read that journal before.

Just my curiosity on "what if i .... at this position" thingie :)
 
Pomzazed said:
^
thx dj, though i've read that journal before.

Just my curiosity on "what if i .... at this position" thingie :)
Click to expand...

Did you scroll down? I posted dozens of articles in that thread over the course of a few posts. I feel pretty confident that some of the info you seek is in there.
 
hey this question's got to do with my post (that nobody's replied to yet btw :(

So Pomzazed, Here's an article, that's been mension here before (actually I read the abstract yesterday) where you might infere some SAR, but activities are in vitro (synamptosomes) so don't know if it's of any use to you.

2006 Elsevier B.V. All rights reserved.
The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain
Fumiko Nagai, a, , Ryouichi Nonakaa and Kanako Satoh Hisashi Kamimura

I suppose you've read: MDMA-like behavioral effects of N-substituted piperazines in the mouse
H.L. Yarosh 2007 and wandered whether anyone's published larger set of molecules. but what kind of activity are you interested in? behavioural?
 
Has there been a good study of the basic BZP structure? Just fairly basic things, like adding a methyl ester here, a hydroxy group there, etc.

(this might be interesting: COC(=O)C(c1ccccc1)N2CCNCC2)

I assume by the above that you mean for benzylpiperazines, right? phenylpiperazines aren't very stimulating, are they?
 
Sorry for the late reply, was working.

As for the paper, i've printed out a copy and read those. But what I'm looking for isnt focused on stimulating (dopaminergic) effects.

Just wonder about the trend of binding (dopaminergic, seretonergic, and also opioid) efficacy when the molecule is modified.

Has there been a good study of the basic BZP structure? Just fairly basic things, like adding a methyl ester here, a hydroxy group there, etc
Click to expand...
^Ham-milton : you get my point, but it isnt only limited to BZP structure as one might enlengthen the methylene (-CH2-) into that.
 
Ham-milton said:
what happened egor? a mini-you?
Click to expand...


Nope. I changed my e-mail due to some shady events happening elsewhere online, and when I typed in the new address, I was retarded and typed it in wrong (twice). I can still log in with egor, but I cant post or use messages. Should be getting straightened out soon...
 
Here is a small selection of SARs of arylpiperazines:

- "Synthesis, alpha1-adrenoceptor antagonist activity, and SAR study of novel arylpiperazine derivatives of phenytoin."
Handzlik, Jadwiga; Maciag, Dorota; Kubacka, Monika; Mogilski, Szczepan; Filipek, Barbara; Stadnicka, Katarzyna; Kiec-Kononowicz, Katarzyna; Bioorganic & Medicinal Chemistry 2008, 16(11), pp.5982-5998

- "A chemometric study of the 5-HT1A receptor affinities presented by arylpiperazine compounds."
Weber, Karen C.; da Silva, Alberico B. F.; European Journal of Medicinal Chemistry 2008, 43(2), pp.364-372

- "Interaction of arylpiperazine ligands with the hydrophobic part of the 5-HT1A receptor binding site."
Zlatovic, Mario V.; Sukalovic, Vladimir V.; Schneider, Christoph; Roglic, Goran M.; Bioorganic & Medicinal Chemistry 2006, 14(9), pp.2994-3001

- "Synthesis and SAR of highly potent dual 5-HT1A and 5-HT1B antagonists as potential antidepressant drugs."
Kling, Andreas; Lange, Udo E. W.; Mack, Helmut; Bakker, Margot H. M.; Drescher, Karla U.; Hornberger, Wilfried; Hutchins, Charles W.; Moeller, Achim; Mueller, Reinhold; Schmidt, Martin; Unger, Liliane; Wicke, Karsten; Schellhaas, Kurt; Steiner, Gerd.; Bioorganic & Medicinal Chemistry Letters 2005, 15(24), pp.5567-5573


All papers were selected just by the sound of the title (quick glimps only) and can be downloaded from at the dark side of the force, as soon as anybody asks for it. I think that the refs contained in the articles could provide further useful info...

PEACE! Murphy
 
Piperazines.

Don't forget about Trazodone, Serzone, Geodon, Zyprexa, and Seroquel. There are even a few antibiotic piperazines.
 
I'd like to know more about the piperazine dissociatives. I love dissociatives but I could only find very minimal info on piperazine ones and they don't seem to be origianl either like the piperazine can really be substituted for any other type amine(infact piperazine is the sub). the only ones I could find where phosphono/carboxylated piperazines and some korean DXM type med(forgot the name but it starts with a Z... Zyban maybe?). Are there any others???
 
yeah, dats it. I'm tried to find some on the net but its no where to be found. I'm not sure how much of an opiate it is(i don't like opiates), but it's an NMDA antagonist for sure
 
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