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phenylcyclohexyl-(2-ketopyrrolidine)

L

Limpet_Chicken

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Oct 13, 2005
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Adder, you might know this, is the title compound known?. Of course, if 2-pyrrolidone were to be used as a precursor, the keto group would have to be oxidized to an alcohol and the keto group reformed..just got me thinking. And what of the unsubstituted pyrrolidone analog of PCP? presumably it'd have a longer half life with no metabolic 'handle' to grab hold of and start chewing on.
 
The 2-pyrrolidone compound has been made by Eli Lilly but I can't imagine it would be an NMDA antagonist as the amide.

The unsubstituted pyrrolidine analogue is known as rolicyclidine and is a Schedule I drug in the United States.
 
The bare pyrrolidine compound, rolicyclidine, that description sounds right up my alley actually.
 
I wonder about 2'-keto-rolicyclidine... maybe a good keta replacer.
2-phenyl-2-pyrrolidino-cyclohexanone.png
 
Why the chlorination? and if there is to be a halogenation then why not vary the halide to something that hasn't been tried, hasn't fluoroketamine been tried? why not say, shove a bromine or iodine in there, or a nitro group, a rhodanido moiety, something else electron withdrawing, depending on how creative one is going to be.

Could just be me. It seems as though I've gone and gotten a thing for stuffing weird difluoroalkyl ethers and even weirder ring substituents in weird ass places they probably have never been put before.
 
Why, is it known? or based on some idea of yours? if the latter then what is your line of thinking? an nitrogenous homolog of BTCP?

Do the indolic homologs of BTCP share the same high DAT affinity compared to a benzothiophenyl?
 
@Limpet

I dont expect the indolyl to be NMDA antagonist (just like benocyclidine), the aryl is too big for it now,
but I am wondering if that might had some additional seretonergic effects akin that benocyclidine(and tenocyclidine) have dopaminergic effect. It can be noticed that with a 1 missing carbon from phenethylamine or tryptamine, if it is a spirocyclic the forced conformation could still make them partial agonist at those sites.

Oops, on second thought this might not be such great idea, it might then be also bind to Adiponectin receptor, messing with fatty acid metabolism (or maybe useful in further fine-tuning more to make a fat control drug?, the structure also looks like an AMPK agonist which inhibit lipogenesis on both triglyceride and cholesterol)
 
A methyl can replace the ketone which then means you get 4 isomers. Hundreds of compounds related to PCP/K were made and tested by a French team. It's in the European Journal of Medicinal chemistry. The people who made K also patented a single compound (almost unheard of) which was 2-chloro-5-methoxy K - or 5-MeOK I suppose. Much more potent analgesic activity. I presume that it is quite widely known... although I don't think the guy (forget his name) who worked out MXE saw the patent. Maybe he did but nobody got around the controls placed on MXE by adding the 2-Cl.
 
Could you tell me the name or at least year and issue of this publication?
Countless analogues have been made, a great deal of substances almost got forgotten. Sadly many of these compounds weren't pharmacologically tested, there are still many dissociatives that were synthesized in a series without providing more than experimental details and so there are still enough compounds which activities are yet unknown and wait to be tested. You don't need to get all fancy, there is still so much to learn about PCP derivatives like PCPr (propyl instead of piperidinyl), of which most people never heard of, although it is covered in the scientific literature. And then think about all the other possible molecules, that weren't studied scientifically. I talk about things like 3-Hydroxy-2'-Oxo-Phenylcyclohexylethylamine (O-Desmethyl-MXE or maybe HXE for Hydroxetamine), 3-MeO-2'-Oxo-Phenylcyclopentylethylamine (MXE with cyclopentanone instead of cyclohexanone) or it's demethylated version. These are only from the top of my head and i only thought about MXE derivatives. You see, still so much to explore!
 
3-MeO-2'-Oxo-Phenylcyclopentylethylamine (MXE with cyclopentanone instead of cyclohexanone) or it's demethylated version.
Click to expand...

playing with the cyclohexane ring size destroys activity as a nmda-r ... the cyclopentane/cycloheptane analogs of pcp are not seen as drugs for this reason
 
That adiporon has interesting structure, it reminds me of some medication molecules but I cannot recall what it is!
(GAT inhibitor something huh?) and that AdipoRon looks much less toxic than i originally thought, according to the wiki article you linked.

And it is true what sekio said. It is mentioned in Rhodium that increasing/decreasing cyclohexane ring size reduced activity as NMDA antag.

Now I’m wondering what will happen if we replace the cyclohexanone ring with a delta-valerolactone or delta-valerolactam ring? I dont think these entity is known, but it has the same size and similar conformation.
 
Hello all. A friend whose HR work has saved countless lives has mentioned several samples of cocaine that after CE & GC-MS among many other types of instrumentation has uncovered a not-al-that surprising alternative. It's safety profile has not been studied but I bet ?1 that it's not good.

(3-exo)-8-azabicyclo[3.2.1]oct-3-yl 4-nitrobenzoate is VERY close to cocaine apart from being a little bit less soluble but since it is a very powerful local anesthetic so numbing so it seems to be accepted, especially within the group who smoke & pin 'snowballs'. As I'm sure people will have noted that pseudotropine and p-nitrobenzoic anhydride are neither expensive nor hard to obtain. I'm sure all of you medicinal chemists will have checked out the MSDS of p-nitrobenzoic acid/anhydride/acid halide and while the body is generally an oxidative instrument it DOES reduce aromatic nitro groups and they hare 'presumed toxic' until trials have been run. As an example, nitrobenzodiazepines kill - less than 1g is fatal. Compare to diazepam where people have survived 20-30 grams! That aromatic amine is bad news.

I think it's worth mentioning because we know that cocaine is cut with levamisole but the compound I mentioned it almost identical to pure cocaine but the chronic toxicity hasn't been studied. AFAIK neither pseudotropine nor p-nitrobenzoic anhydride (or the acid halide, I suppose, but that is more work.

I have discovered that certain test kits WILL spot it but who knows if it's 100% or just 5% cut in to bulk out to extra Kg.

Sorry to bring bad timing but pyrophenidone has been well researched and it substituted for cocaine in animal studies and people in the throws of cocaine dependence have discovered that it stops the cravings. Pyrophenidone was arrived at by extensive research BUT while animal models were carried out, we just don't know. I think the only interesting aspect is that the 1-phenyl is a bioisostere of an n-propyl moiety and suggests that it binds to a flexible lipophilic pocket. Development was:

Step 1: 1-(1,2-diphenylethyl)pyrrolidine (fuckup - they were supposed to add a piperidine ring) with mild stimulant activity
Step 2: 1,2-diphenyl-2-(pyrrolidin-1-yl)ethanone (O lone-pair interacts with N lone-pair which is why tertiary amines of this class are so active
Step 3: Addition of (cyclo)alkyl group on the 2-benzene. The indane does not engender serotonin activity and just make it less soluble (so painful)
Step 4: Animal models show that 1-(4-methylphenyl)-2-phenyl-2-(pyrrolidin-1-yl)ethanone has higher intrinsic activity while the p-Me is a convenient point for the body to oxidise so kinetics are dealt with by a 'sacrificial moiety).
Step 5: Add halide/pseudohalide at the ortho position of the 1-phenyl. Of no benefit
Step 6: Add methyl ether to meta position of 1-phenyl to see if it increases opioid affinity (it doesn't)
Step 7: Lose ketone & Swap pyrrolidine ring for piperidine group SO NMDA activity is established (diphenidine)
Step 8: Swap piperidine for N-monoalkyl (methyl, ethyl, propyl, isopropyl. Isopropyl is most active.
Step 9: Having established that the N-isopropyl was the best, adding a p-methyl to the 2-phenyl to increase DRI activity.

So the idiots who ran with diphenidine don't care as long as they get the money. People don't seem to realize that for most people, the DRI activity of NMDA ligands is important. The euphoria reduces negative experiences.

Anyone interested will find a large paper covering 1-(4-methylphenyl)-2-phenyl-2-(pyrrolidin-1-yl)ethanone isomers and their activity. Original is in European Journal of Medicinal Chemistry but of course you end up with 4 isomer and while resolving trans/cis pair isn't too hard, resolving the trans-(S) & trans-(R) isomers is more problematic.

I point these facts out because I suggest that we need to be on the lookout. I haven't mentioned synthesis and I've been very clear on the fact that NONE of the RCs have been properly tested so when you take a random powder (or worse, a coloured pill... you add colour to disguise product with precursors still in there.

We really do have a group of people who are able to design and organize testing for new agents. We need to be a little more rigorous about 'new finds' because frankly, most aren't actually new. MANY have failed trials. We don't want people to be harmed so we do need to crowdfund proper instrumentation. 100 people paying ?5 will get a decent NMR & GC-MS and if needs be, CP and other sensitive options. I have seen MDMA dealers who had no produce for a festival so they bought a stack of LSD microdots and mixed in the speed they had and a little bit of MDMA. For 'fun' they would put 3 microdots into one cap.... I mean, this is terrible.

Thank you all for your time,
CC
 
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Its only terrible if you are in the 99,99% of partygoers who didn't get the cap with the three microdots inside=D

I'd think myself very lucky if I picked the right capsule, I'd be absolutely delighted in fact.

Hell they could have raised money with that, doing a raffle, to buy more goods to sell.

Wish I could get people to crowdfund ME my own GC/MS, damn.

As far as coloured pills go, I don't think that has everything to do with it. A LOT of that is about branding. White sharks, blue mitzis, pink double cherries, its branding, like stamps. Not to cover up a pink tinge from a little overacidification. Hell, while I'm not pressing pills myself, but even though I
can produce snow-white produce, if I WERE making presses, I'd still be making my own designs, so I could indulge in some art. I might not be a talented oil painter, or watercolour artist, but you bet I could come up with some novel presses.

'bright lurid yellow with irregular orange stripes-ed horned melons' maybe? grey death's heads SS skulls on black backgrounds with a banana in their mouths that glows with the SS skull's teeth and fangs under blacklight? 'inland taipan' 'leiurus quinquestriatus' glyph ?'

Liphistiidae spp, that bright blue and orange malaysian basal spider in the sister group to all other Mygalomorph spiders, nonvenomous, retains segmented abdomen plates from the time spiders and scorpions diverged evolutionarily?

Pink pig snouts poking out from under a copper's helmet with beady red eyes and 'big bastard' written on the obverse side?

A cop getting shot in ink?

While I don't make MDMA from safrole, if I did, I'd be inclined, after thoroughly redistilling the base under vacuum, to add just enough safrole from the original oil, to give it a lovely scent of sassy oil, because apparently people go nuts for sassy oil-made-MD especially. Not enough to be toxic obviously, just enough to give them a scent, and not enough for that scent to carry far enough for other people to detect the odour coming out of people's pockets, etc. just enough to impart that lovely root-beer perfume to the pills.


Clubcard...read the edit..you do realize that could also, in NT-speak, now that I sat down and analysed your words and translated from autie into NTese, that could read as 'throwing acid in people's eyes is wrong, but there are some people who have it coming'=D
 
sekio said:
playing with the cyclohexane ring size destroys activity as a nmda-r ... the cyclopentane/cycloheptane analogs of pcp are not seen as drugs for this reason
Click to expand...

Ah yes, I remember to have read that on erowid. Thanks for reminding! Still, Hydroxetamine would be worth a shot and by thinking about a synthetic approach to arylcyclopentanoneamines I realized a smooth way that I never read of:

React (subst.) Phenylmagnesiumbromide with cyclohexene oxide -> 2-(subst.)Phenylcyclohexan-1-ol

Oxidize that to 2-(subst.)Phenylcyclohexanone

alpha-bromination of this substituted cyclohexanone affords a substrate that only needs to be treated with your favorite amine to yield an Arylcyclohexylamine. For MXE the chems would be 3-MeO-bromobenzene and ethylamine. What do you chemheads think about that?
 
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