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I Like to Draw Pictures of Random Molecules

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Right, the ester bond would be unlikely to survive the gut, much less first-pass metabolism. That's why I'm not suggesting that it would be orally active (though the amide that I posted earlier might be.) Taking the drug intravenously gives it a much better chance of getting into the brain unmolested by the liver's enzymes.

DL-ark said:
Has shulgin adressed something like alpha-carboxylated MDPEA/MDA? Or an alpha carboxylated 2c? oh man an alpha-carboxyl 2c-e could be a very good alternative for getting around the law....
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I'm not aware of any alpha-carboxilated species coming from Shulgin. They wouldn't exactly be easy to synthesize unless you have the corresponding amino acid to begin with. For example the following compounds could be trivially synthesized from phenylalanine, tyrosine and DOPA respectivly.
Molimage

Molimage

Molimage

The first one has an interesting meth-amphetamine-ish look about it.
 
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I'm interested in what an intermediate molecule's duration and activity would be like.
2-Benzylpiperidine is very weak and short lasting, Methylphenidate and Ethylphenidate are somewhat stronger, but also short lasting. Desoxypipradrol is extremely long lasting and superpowerful. I would like to see something intermediate in duration. 6 hours to 9 hours. Not 2 hours. Not 16 to 30 hours.
Like a long lasting study-like stimulant.
Here's NRG-64, based on desoxypipradrol.
2ymg6yd.png
 
6 hours to 9 hours. Not 2 hours. Not 16 to 30 hours.
Like a long lasting study-like stimulant.
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concerta / focalin xr ? used as indicated on the label, of course, not chewing or crushing and certainly no extractions.

or ... caffeine ;)
 
it might change the SAR a bit more than the molecule you proposed, but what about adding an oxygen to one of the rings on desoxypipradol to give your enzymes a better spot to break it down at?
 
3HZGYa6.png


I think oxazoles like these have actually been made and investigated... if memory serves they are indeed like longer activity MPH analogs.
 
iYh5e4Z.png


The LSZ or 2,4-dimethylazetidide version of 4-AcO-DET (not the green part)? I'm curious to know what the effect of swapping the red methyls around do.. I would guess only one configuration is going to be highly active at the receptor? I wonder how much stuff you can have up there at the nitrogen before it would become too weak (add another methyl like whats in green?)
 
Not sure, but LSZ may be way different than tryptamines because LSD with two ethyls is highly potent, but is potency relatively quickly lost when there are other amide substitutions? I can't really compare it quantitatively, you would need to make a table comparing LSD analogue potencies with the tryptamine series.
What I mean is: the fact that the ethyls of LSD are a critical part of the structure and tweaking them to be just right is meaningful doesn't mean the same is true for other psychedelics with N-substitutions. You can slap a lot more substutions on tryptamine amines and potency still stays reasonable.
Look at the NDEPA like compounds, and overlay tryptamines like 4-AcO-DET with LSD. The amine you are putting an azetidide on here matches the 6-position nitrogen of LSD, I believe, not the amide nitrogen.

Still fun idea, but the difference in effect and potency may be more marginal than you'd think.

I don't have drawing software on hand where I am sitting now, but I'd be interested in common psychedelic tryptamines with an N-acetyl like ALD-52. Shouldn't be much effort and it might tell us something about whether that modification is meaningful, or mostly based in myth. :)
 
Here's a molecule that could be NZT-49 in real life. Norzatrensine.
1zldd76.png

It's based on nomifensine. I assume that the blood dissolving toxicity comes from the amino group directly attached to the phenyl group. Cyclylization could eliminate this while hopefully allowing this stimulant molecule to retain it's non addictive properties.

This one is methylpheniclone. It's a longer lasting version of methylphenidate. Hopefully, it's duration does not resemble the ridiculously long acting desoxypipradrol.
2qxb51f.png
whzl2a.jpg

Here's beta(cyclopentyl)amphetamine. It's kind of a hybrid of cyclopentamine and amphetamine and should have a longer duration.
9ll8ac.png


Here's redicusomfinil! It's rediculously crazy! Some of it's metabolites would be fluorenol and beta(cyclopentyl)amphetamine.
rrtl08.png


Here's Cyclopentaminsomfinil!
2vt3xbo.png


Here's indanylaminopropanylinsomfinil (IAPI-57)
141tipx.png


Here's wininsomfinil.
2bs3es.png


Here's Killinsomfinil!
2mplmd5.png


Here's rivaninsomfinil. It's a combination of insomfinil and rivanicline.
2814qpv.png


This last one is pretty much just for fun. Galactenol! The extreme wakefulness enhancer!
vhuz9.png
 
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thenightwatch said:
squint your eyes a bit and that almost looks like dextromethorphan
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This is levomethorphan and not dextromethorphan. And I doubt that DXM's methoxy group binds like methoxetamine's methoxy group. The cyclohexane ring of DXO is not even necessary for high affinity at NMDA receptors, the aromatic ring of PCP and the aromatic ring of DXO may bind to different residues, this is likely. (+)-metazocine lacks the cyclohexane ring and has a much higher affinity to NMDA receptors (Ki = 41 nM) than DXO and (+)-normetazocine is even more potent (Ki = 30 nM, source). DXO being 10 times more potent by weight than DXM could have a 400-600 nM affinity, that's a rough estimation though. Anyway, that leads to a conclusion that other metabolites of DXM, namely nor-DXM and nor-DXO may have a much greater role in dissociative effects than it is thought now.

I wonder whether the 2-phenyl analogue of metazocine or normetazocine would have a boosted affinity at NMDA receptors. Or the 6-phenyl analogue, a relative of (+)-methadone.

Bez_nazwy_3.jpg


Perhaps dextrorotatory benzomorphans and morphinans could be related to dizocilpine in the way drawn below. Keep in mind dizocilpine's molecule is bent and the angle between two aromatic rings is close to 90 degrees.

normetazocine_vs_mk_801.jpg


All recreational dissociatives are hardly selective for NMDA receptors. Dizocilpine is far from being as recreational as ketamine for instance, diphenidine isn't much recreational for me either. What if recreational effects of dissociatives could be separated from NMDA antagonism? Perhaps they're more related to effects mediated through sigma and/or kappa receptors? Or these effects and NMDA antagonism are complementary and potentiate one another, but NMDA antagonism is not the driving force behind pleasurable effects.
 
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2-methylamphetamine
2-methylmethamphetamine
2,6-dimethyl(meth)amphetamine

Not sure how dangerous these are, though.
 
Ok, so this is a little 'off-the-wall' so to speak but I realised looking at acid that it's insanely similar to tryptamines (I knew this before of course but this structure just hit me), so I cut out the two phenyl rings and took out a carbon from the propylamine chain attached to the second amine group. Also I realised that after forming a ring with the hydroxy at the 4 position, the third amine group would need a bond to form the extra ring with so I added another hydroxy at 5. So, any ideas if this would work or not, or is it too far away from tryptamine itself?

lHsc7Bm.jpg
 
double ring hydroxylation, esp. ortho- or para-, is pretty much certain doom for a drug like molecule due to the ease with which it will form a quinone (oxidative cycling... people were all up in arms about dopamine being neurotoxic via this mechanism), relatively high polarity, and ease of metabolic destruction due to not one but two "handles" to accept e.g. sugars, sulfate, or glutathione. (c.f. bufotenin is weaker than 5-MeO-DMT in humans and lower b.a.)

this is also why IV dopamine is a rather poor central stimulant :)
 
Damn. I was worried about this to be honest! However having said that I recently noticed a tryptamine analogue that bears remarkable similarities to quininones. Having said that the structure is completely different to what would be created by metabolism of this compound. It's http://en.wikipedia.org/wiki/Ro60-0213, also http://en.wikipedia.org/wiki/AL-37350A, which is a lot more similar to the compound in question (and the end product), minus the oxygen in the phenyl ring. It's also a 5-HT2a agonist too, which gives me some promise.

Wait, you're talking about complete cleavage of the amines right? If so then I think it would produce some poor quinones.

Also were you talking to me or someone else?
 
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