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Practical MXE replacement

At 200mg it was a nice, easy ging stimulant without much abuse Potential. No mu agonism noted.
 
plumbus-nine said:
As said, it's probably from the 3-HO-2'-Oxo-PCE metabolite. there's some paper describing the complex metabolism of MXE and 3-HO is one of the metabolites.
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Yeah it's here, but HXE is still only a minor metabolite. Incubating MXE for 2 hours with liver microsomes and MXE is still present at levels 7x greater than HXE. The primary metabolite is Nor-MXE.

Although there's no evidence that HXE has MOR affinity either..
 
izo said:
At 200mg it was a nice, easy ging stimulant without much abuse Potential. No mu agonism noted.
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I could not feel it either, but https://repositorioslatinoamericanos.uchile.cl/handle/2250/886407 and there are many more references.

The benzene and amine are trans. Try overlaying it with isonortilidine - it fits perfectly. The bridge of the norborane isn't specified in most papers but it's trans (is that the right term) to the amine. That makes sense as MOST drugs are the trans isomers (if chiral). In the end, that norborane is simply a nice rigid scaffold.

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If you can imagine placing an -OH onto the benzylic carbon (the carbon the benzene ring connects to) and then esterifying it, you will see it overlays isonortilidine.

Of course, fencamfamine/camfentamine are made in an elegant but SPECIFIC manner. Cyclopentenediene & [(E)-2-nitroethenyl]benzene in what many chemists consider to be the 'Mona Lisa of chemical reactions' i.e. the Diels-Alder reaction. It's a reaction that seems to draw chemists to it. Bentley et all performed a Diels-Alder on thebaine to produce etorphine, Even tiilidine is made this way (which is why nortilidine has to be made via tilidine) It is the cornerstone of steroid chemistry.... BUT the scope is very limited.

 
BTW I believe it's possible to perform a Diels-Alder with [(E)-1-bromo-2-nitroethenyl]benzene so the benzylic carbon can bear a -Br.

So is someone can convert -Br to -CN (which hydrolysis + esterification yields ester) or concern -Br to a -OH which can be esterified with propanoyl chloride..... well I guess you would end up with a tilidine/INT analogue.
 
Of course, what I would REALLY like to find is a simple way to add a benzylic ester (or reversed ester) to camfentamine. Replacing [(E)-2-nitroethenyl]benzene with a derivative with an ester/reversed ester )or precursor of same) and those do not exist.
 
izo said:
Is the 5ring isonortilidine a typo? The double bond is required for mu activity though.
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No - 5mg 1R,2S INT is as active an opioid as 10mg morphine. Of course, it's the 1S,2R isomer that produces DRI & DRI activity.
 
arrall said:
@fastandbulbous may have some excellent insights here ;)
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I appreciate your confidence, but you have more confidence in me than I have in myself!
One little thing though: the fact that 4-MeOPCP is active, means there is space in the receptor to tolerate a larger O-alkyl group, ie ethoxetamine [ 2-(3-ethoxyphenyl)-2-N-ethylaminocyclohexanone ] should have very similar activity to methoxetamine.

PS. Weird to see someone has spent time analysing my thought processes in the creation of mxe!
 
Are you the guy who created MXE fastandbulbous? Damn if that's true, you indirectly gave me fantastic time and forever in debt for it :) Maybe I'll brighten up the thread with some structural information when I have time (not now...). I'd love to know where MXE binds in NMDA and other sites, and test for example your hypothesis about steric hindrance of 4-Meo-PCP in the binding site. I'd like to play the game of finding a new MXE analogue using in silico toys a bit, could be fun. It's funny because you chemists are basically working blind with only ligand information, but you manage to find rocking compounds, that's crasy to me.
 
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If I'm honest, it was a long time ago and my memory has been shit & episodic, since my wife died, earlier in the year. Just starting reading papers about NMDA antagonists again...
 
fastandbulbous said:
Added a new word to the English language.
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i do that all the time to german. just invented a new term for a neurodegenerative syndrome over here in germany. i call it margel. dont know if it will push through though.
 
fastandbulbous said:
If I'm honest, it was a long time ago and my memory has been shit & episodic, since my wife died, earlier in the year. Just starting reading papers about NMDA antagonists again...
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I'm sorry about your wife, man. <3

It's always nice to see you pop your head back in here. :)
 
fastandbulbous said:
If I'm honest, it was a long time ago and my memory has been shit & episodic, since my wife died, earlier in the year. Just starting reading papers about NMDA antagonists again...
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I’m really sorry to hear that man.
It makes sense that your memory would be a bit wonky following an event as sad as that.

On a brighter note, I’m glad to see you back on here.
Have you had the chance to try out DMXE?
I’ve been running some experiments with it and while I have yet to try the original MXE, both DMXE and 3-MeO-PCE have been very impressive.
 
Yeah, DMXE doesn't really do much of what MXE does. As far as I can see, what is required is an atom that has lone pairs of electrons, attached at the 3 position of the aromatic ring (although, I really would be cautious about a nitrogen attached there, seeing that lots of aromatic amines are a tad toxic). Never tried the compound with a fluorine atom in the 3 position, but with three lone pairs, it looks a tad promising.
 
One more thing, 3-methoxyarylcyclohexylamines are quite impressive: the one that impressed me was 3-methoxyPCE. Good management of neuropathic pain, with minimal sedation (but then it is MXE without a keto group on the cyclohexyl ring!)
 
fastandbulbous said:
Yeah, DMXE doesn't really do much of what MXE does. As far as I can see, what is required is an atom that has lone pairs of electrons, attached at the 3 position of the aromatic ring (although, I really would be cautious about a nitrogen attached there, seeing that lots of aromatic amines are a tad toxic). Never tried the compound with a fluorine atom in the 3 position, but with three lone pairs, it looks a tad promising.
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Is that required for NMDA antagonism, or some serotonin action, or some unknown magic factor?
 
As I said in another thread, the 3',4'-dichloro-pcp has never been made before according to pubchem website.

However, where in the world can they do this sort of chemistry. It's too strongly prohibited where i live.

I recently discovered an agent called 2-MDP that I had not previously considered.
 
Must not be for NMDA antagonism, because DMXE is plenty dissociating. I actually find it (so far) the closest to MXE of any disso I've tried, though it definitely lacks something. I have yet to try "FXE", though I got some recently, just haven't found a good time for a disso trip yet.
 
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