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I Like to Draw Pictures of Random Molecules

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Surprised this rather promising tree hasn't been barked up a bit more:

What's with the allyloxy? and can you think of a ghetto hypothetical name for this, it looks very strange. why not try the amine on the left position instead of where it's at (it's currently at the same spot it'd be on 2C-B-IND but the guys on the last page said the amine would be better to the side)

Obviously I know nothing at all about this.

I'm not too sure here, but possibly 2-(5-allyloxy-2,3-dihydro-4,6-dimethoxy-1H-inden-1-yl)ethanamine?

2-(X-1-yl)ethanamine would mean you have a complicated structure connected to ethylamine. The 1-yl is indicating that the bond between the complicated thing and the ethylamine falls at the 1-position on the complicated thing, and the 2-(...) means that the bond between the complicated thing and the ethylamine is off of the 2-carbon of the ethylamine.

Then for the 'complicated thing' you'd have indane, which is 2,3-dihydro-1H-indene, and the substituents are two dimethoxies and an allyloxy, so alphabetically you'd have 5-allyloxy-2,3-dihydro-4,6-dimethoxy-1H-indene, chop off the final 'e' and replace with 1-yl, and yeah, 2-(5-allyloxy-2,3-dihydro-4,6-dimethoxy-1H-inden-1-yl)ethanamine.

Is this as wrong as I expect it to be? There's *always* a gotcha when it comes to IUPAC...

EDIT: Oops, shit that's a methylamine not an ethylamine! So (5-allyloxy-2,3-dihydro-4,6-dimethoxy-1H-inden-1-yl)methanamine, not what I wrote earlier. I guess we could be picky and put it as (2,3-dihydro-4,6-dimethoxy-1H-5-[prop-2-en-1-yloxy]-inden-1-yl)methanamine but come on, just call it allyloxy! Or for that matter instead of this 2,3-dihydro-1H-indene nonsense just call it indane and get (5-allyloxy-4,6-dimethoxyindan-1-yl)methanamine. Blah.. or not.
 
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Structural rationale: First, allylescaline was the most potent of the mescaline analogs, though cyclobutyl may be somewhat better (and more stable).

Secondly, jimscaline had improved potency relative to mescaline, while 2CB-Ind had reduced potency relative to 2C-B. But TCB-2 had improved potency relative to 2C-B! What can we make of this?

The key, I suggest, lies in the distance between the nitrogen and the upper-methoxy group, if the molecule is oriented so the amine is at the "top". In 2CB-Ind, the indane actually pushes the nitrogen closer to the methoxy, which is unfavorable, but in TCB-2, the cyclobutane pushes it away, which is favorable. But in mescaline, the ortho methoxy has migrated over to the meta position, increasing the nitrogen-oxygen distance more and making the indane restriction favorable! We can capitalize on this by using the optimal 4-substituent.

http://pubs.acs.org/doi/abs/10.1021/jm060272y

Also, thiophene S-oxides are hepatotoxic and should be avoided. BTCP is a prime example.

Thank you, I appreciate this. So you're saying the mescaline positioning of methoxys is better than 2C's for the positioning of the amine the way you have it. So has the actual 4 methoxy version of what you're talking about been thought of or made? I don't recall seeing anything like that besides 2CB-Ind. I always love the SAR lessons, keep it up!

To Deinonychus: You, my friend, have also increased my knowledge of how this works. Thanks. One question though, why is it 4,5,6 for the -oxys and not 3,4,5 like in mescaline or allylescaline? EDIT: Nevermind, I reread it and kind of get it. Confusing though. I understand what you're saying but I couldn't quite number it myself

A bit of SAR input of my own, the TFM-version would probably be much more potent than the allyloxy-version of this, based on what I know of mescaline/phenethylamine SAR. You're probably tired of hearing about the trifluoromethyl substituent on the 4 position of phenethylamines but I think there will be few substitutions as effective as that one based on what I've seen. Maybe pentafluoroethyl or trifluoroethyl if penta is too bulky? I only bring this up because you're basing it off of allylescaline because of it's potency. I think trifluoromethylscaline would be a great deal more potent.
 
Once again a combination of looking at existing structures, a ton of fucking around, and a lack of any decent SAR knowledge:

eaf3UAP.png


Or how about these fellas:

QxUHrib.png

yD2VL29.png
 
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I think it depends a lot on stereochemistry. The top one looks like oripavine, the bottom 2 smell inactive (too wierd of a substitution)
 
Been bored and felt like making a few more quick ones, these ones I'd be more hopeful about, at least the first two:
JnhUI2S.png


Reasoning for the first two being the aminoindanes seem to be quite serotonergic, with little DA/NA activity, and that adding a b-keto group often tends to shift the focus of the activity more in the direction of DA/NA. The 4-MMC analogue was chosen since it's fairly dopaminergic already, the 5-MAPDB analogue was chosen as an alternative if the 4-MMC based one was too dopaminergic.

The last one is just me playing around since seeing the aminoindanes with a b-keto group reminded me a little of phenmetrazine and aminorex derivatives.
 
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indolylpropylaminopentane, or IPAP. Possibly a serotonin activity enhancer and MAOI?
4yeYkb7.png


MetachloroBcarboline (aka mCPP's even more unpleasant brother):
N53MKgk.png
 
Since my lack of SAR knowledge makes speculating on interesting structures a little hard, but I love making them, I figured I'd just make a whole load of structures without putting much thought into them, and maybe if I hit anything somewhat interesting in the process someone'll notice and point it out. ;)

So here's a bunch, some of which I'm fairly certain would be inactive:
jTVQlm4.png


Of those the ones that seem like they might have some potential to me are a couple of the Methylphenidate analogues and the 2-Benzylpiperidine and 4-Benzylpiperidine analogues. Dunno though.

Decided to pop another one in before I head off for the night:
QPDU2Oa.png


Not sure if I'm right but I just went under the assumption that while taking something like Mephedrone and switching out N or 4-Methyl groups for Ethyl ones results in less enjoyable effects, with something like Buphedrone that seems to be almost purely dopaminergic maybe these sorts of additions would be worthwhile. I imagine 4-Ethylbuphedrone might be interesting too, more so than 4-Methylbuphedrone (4-MeMABP) would be anyway. All just newbie speculation here though.

Drawing structures is pretty addictive, especially when there's at least some thought behind them, even if it's usually quite flawed in my case. Did a couple more, finally getting off to bed now because I'm exhausted:
UlPVdbH.png
 
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jesusgreen: Arecoline analogues like the one you've shown are, IIRC, actually somewhat interesting DRIs... though personally I think arecoline's pro-muscarinic activity is far more interesting in and of itself, too bad it's carcinogenic as all hell. I see you've chosen the cocaine-pattern which is of course a good one.

I can't of course say something about all of those, a few are very likely inactive -- in particular tertiary amines from the phenethylamine class tend to be active only by dealkylation cf MDDM and phendimetrazine, excepting the use of pyrrolidin-1-yl since it is compact and conformationally advantageous. The beta-methoxy alpha-methyl phenethylpyrrolidine may be good.

Antimuscarinics (tricyclics and deliriants) induce mania so I've long wondered if perhaps muscarinic agonists like arecoline could be useful mood stabilizers, if the efficacy is low enough to prevent convulsions that is. It would sure beat the hell out of the atypicals and anticonvulsants (valproate, ugh) typically used for this purpose.
 
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bw8OmxU.png

Someone told me about this piperazine-based molecule from IUPAC, and with the limited knowledge IUPAC-reading & structure building from that, that I have, I attempted drawing it in ChemDraw.
Is it a completely impossible molecule? (Hint: its base-structure is para-methylpiperazine)

The naphthalen-functional group is perhaps to cause some analgesia? They were pretty common in some of the JWH-series cannabinoids, but this is a different beast.
 
Fencamfamine looks quite similar to Tilidine and has some opioid effects. What would happen if you put an ethyl-carboxylate chain on Fencamfamine at the same place where Tilidine has it? Would an additional 3´OH-hydroxilation on the phenyl ring of FCF or Tilidine make sense? (like o-desmethyltramadol).
(I drew the tilidine without the dimethyl ´couse it´s only active with none or just one methyl-unit.)

ethyl 3-(ethylamino)-2-phenylbicyclo[2.2.1]heptane-2-carboxylate
ethyl 3-(ethylamino)-2-(3-hydroxyphenyl)bicyclo[2.2.1]heptane-2-carboxylate
ethyl 2-(methylamino)-1-phenylcyclohex-3-ene-1-carboxylate
ethyl 1-(3-hydroxyphenyl)-2-(methylamino)cyclohex-3-ene-1-carboxylate

2yo790w.png
 
Anyways :
W6tTzEX.png

b5BALrJ.png

Thiols are usually covalent receptor substrates which makes them very dangerous. That second one would condense to give an aromatic aldehyde which would then polymerise.

The third I doubt would be active as a stimulant and it's a bit far from anything to hint other activity.

I don't fancy that thioketone either, they stink and the a-dimethyl isn't much good either.

Soulfake's definitely appear to have potential. Close comparison to NMDA antagonists will likely show pretty quickly they won't have much activity there - the amine is in the wrong place.
 
I really don't know why I used the alpha dimethyl, I was drinking haha. That would make the substance somewhat more selective for norepinephrine right ?

Thioketone looks cool, because if I remember correctly there is a synthesis where you can replace normal oxygen ketone with sulphur. Would make synth easy, if it doesnt destroy the compund. Yes it would stink and probably you to from all that stinky sulphur containing sweat :D
 
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