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I Like to Draw Pictures of Random Molecules

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Yeah that would be the proper name. It's a pretty simple derivative of prolintane so I'm certain it'd be active, I just wonder about its potency. Prolintane was sold as catovit in 10mg tablets I think, so it could potentially be a bit more potent than amphetamine. The butyl analogue is mainly just an NE releaser though so maybe it's a dead end. Especially when you consider that prolintane is an NDRI.

Still, it's interesting for me to see how versatile that prolintane structure is - lots of our favourite amphetamine modifications could probably be applied to it. It'd be interesting to see what the expert's favourite addition (:p), an MDO ring would do to prolintane. An SRI NDRI or an SRA NDRI?

Edit: Apparently Shulgin talks about alpha alkyl lengthening in pihkal. It'll only be relevant to psychs but I'll see what he had to say.
 
So I was trying to draw a methylhydroxy- version of Oxilofrine, and ended up with this instead:

oxilofrineattempt.png


Can someone explain what I did wrong? I was trying to follow roughly the difference between MA/MDMA, but obviously I've cocked it up somewhere.

Also, is the above compound feasible? I think oxilofrine is a fairly good NE/DA releaser, and I was shooting for some SE action too.
 
glenjih, that compound is beta-hydroxy-MDMA, aka methylenedioxyephedrine. It is a known metabolite of methylenedioxymethcathinone (bk-MDMA, Methylone).

Generally beta-hydroxy phenethylamines are poor releasing agents of DA/5HT, they are OK NE releasers and adrenergic/5HT agonists though. They also have consideraly more action at adrenergic (peripheral) receptors.

Oxilofrine looks to me like it's a para-hydroxy ephedrine, and woud make for a relatively poor stimulant.
 
Transform said:
Edit: Apparently Shulgin talks about alpha alkyl lengthening in pihkal. It'll only be relevant to psychs but I'll see what he had to say.
Click to expand...

http://www.erowid.org/library/books_online/pihkal/pihkal001.shtml

i'm not sure if he tried alpha-ethyl versions of all of his sub-classes though. shulgin seemed to be very quick to call something a dead end. i think alpha-ethyl psychedelics might work if you tinker around with the other parts too.

p.s. that link doesn't really say much about stims.
 
As far as I know, alpha-alkylation of phenethylamines beyond a-methyl greatly decreases potency at serotonin receptors. Compounds with long chains do retain activity at NET/DAT though (prolintane).
Even highly potent compounds like DOM/DOB lose hallucinogenic activity when the amphetamine is changed to an alpha-ethyl, see commentary for ARIADNE. At best they could be mild anti-depressants, or so Shulgin speculates. I feel this is probably due to f/x at NET/DAT or other non-%HT targets.
 
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shulgin only tried alpha-ethylating a few compounds.

suppose DOI-NBOMe was made and not found to be very potent, so the scientists assumed that 2C-I-NBOMe must be less potent...

i think shulgin was too quick to call certain roads dead ends

there is only so much time to test and taste though
 
'A few"? He at least produced alpha-ethylated DOM (ARIADNE), DOB, AMT/tryptamine (AET), MDMA/MDA (MBDB/BDB), mescaline (AEM), and probably more.

I'm all for 'make em and taste em' but SAR does have its place too.
 
i'm not sure we should include AET, tryptamine SAR is fairly different than phenethylamine SAR

DOM/DOB are pretty closely related, as are MDA/MDMA. and then AEM... he basically alpha-ethylated in three directions only, not five.

as just one quick one off the top of my head, perhaps alpha-ethyl Ganesha analogues are actually more potent? SAR is weird between 2C-G-X/(DO)G-X

[[lol DOG, no wonder he went with just G as the acronym for Ganesha :D]]

...then again, who would even want a more-potent or longer-acting analogue of Ganesha. =p

perhaps it is a dead end. i still have a hunch that direction could potentially have some gems, though. *shrugs*
 
I've recently been thinking about some LSD analogues, particularly with respect to opening up the rings a little. It seems most modifications have been of the diethyl amide, the 9,10 double bond, 2,3 double bond, on extensions on the 1 or 2 position of the indole. I've preserved the C5 and C8 stereochemistry, as alteration of those abolish all psychedelic actvitiy.

openringlsd.png


Also, a modification where I took out the carboxyl group of Lysergic acid. I have a feeling that this one, if it is a 5-HT2A agonist, won't be psychedelic though.

nondiethylopenring.png


benzopyranopenringlsd.png


Another open ring LSD analogue, but with an oxygen substituted off the 4 position, a la psilocin, but incorporated it into the ring. However, this eliminates the 9,10 double bond, which abolishes psychedelic activity. I wonder if this one might retain some activity though.

Edit: Better pictures uploaded.
 
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8-Descarboxy-lysergic acid is apparently active at 5-ht2a as a hallucinogen with something like 1/10 the potency of LSD in mice.

I think the problem with ring-opened ergolines is that part of the reason that the ergolines are effective at all is their flat, planar configuration granted by the ring systems constraining each other. Opening the rings of LSD leads to greatly reduced activity/potency as far as I know, because the molecule rapidly becomes less planar as you break the rings apart.

The 9,10 double bond in particular has been implicated in the high affinity of ergolines for 5-HT receptors - loss of pi bonding at this site causes a dramatic drop in potency (see: lumi-LSD vs LSD). I don't think your 3rd compound will be active for this reason.

I think there may be some existing research on 1- or 3- piperidinyl indoles as agonists at 5-HT. I remember there was at least one - possibly the stericalyl hindered version of AET - that had a reasonable potency.
 
sekio said:
8-Descarboxy-lysergic acid is apparently active at 5-ht2a as a hallucinogen with something like 1/10 the potency of LSD in mice.
Click to expand...

I actually read this in a Nichols review shortly after posting. I was suprised, especially given how slight changes to the diethylamide can drastically reduce potency.

I figured that the flat, planar nature of LSD might be required to adequate binding and activation of 5-HT2A, I was just wondering what other 'skeletons' of 5-HT2A agonists might be buried in there, considering that both phenethylamine and tryptamine skeletons are embedded in LSD. Maybe something incorporating the diethylamine moiety?
 
Sturnam said:
I've recently been thinking about some LSD analogues, particularly with respect to opening up the rings a little. It seems most modifications have been of the diethyl amide, the 9,10 double bond, 2,3 double bond, on extensions on the 1 or 2 position of the indole. I've preserved the C5 and C8 stereochemistry, as alteration of those abolish all psychedelic actvitiy.

openringlsd.png


Also, a modification where I took out the carboxyl group of Lysergic acid. I have a feeling that this one, if it is a 5-HT2A agonist, won't be psychedelic though.

nondiethylopenring.png


benzopyranopenringlsd.png


Another open ring LSD analogue, but with an oxygen substituted off the 4 position, a la psilocin, but incorporated it into the ring. However, this eliminates the 9,10 double bond, which abolishes psychedelic activity. I wonder if this one might retain some activity though.

Edit: Better pictures uploaded.
Click to expand...


Is there not a way to add the 4 position psilocin but still retain the 9,10 double bond ?

That would be worth a bioassay .
 
Facts :
- Substitutions on the 6-position in ring D of LSD creates some magic. In particular, ETH-LAD (cf. TIHKAL) seems roughly twice as potent as LSD-25 (true in humans cf. Shulgin, and rats cf. Nichols).
- LSD is a tryptamine, but it also contains the PEA skeleton, which share that same 6-position-in-ring-D nitrogen.
- NBOMe substitutions on PEAs multiply their potency by roughly 40 and adds a lot of magic to 2C-Xs.

Therefore, I give you:

Za1Km.png


LSD-NBOMe.

This has the potential to be active in the nanogram range. Could it be the carfentanil of psychedelics?
 
I'm talking out of my ass here but I don't think this would be active at excitingly small levels.

Look at phenethyl-LAD...
http://www.erowid.org/library/books_online/tihkal/tihkal51.shtml

"Something" at half a mg. In addition the NBOMe-tryptamines were all failures, and they share the indole structure with LSD.

Also I believe Nichols or any of the other real scientists who have studied LSD and the NBOMe series would have jumped on this immediately if there was reason to believe it would be exciting.
 
Doubtful, the size of the amine substituent on LSD seems correlated to activity -by the time you get to PARGY-LAD there is a pretty obvious drop in activity

I don't expect NBOMe to become a popular motif in drug design. It doesn't seem to work with anything but phenethylamines.
 
sekio said:
Doubtful, the size of the amine substituent on LSD seems correlated to activity -by the time you get to PARGY-LAD there is a pretty obvious drop in activity
Click to expand...

there was a time when it was thought that any n-substitution on a phenethylamine was considered to be a bad idea =p the size of a particular group is not the whole story.

besides PARGY-LAD is still active at under a milligram :)

i think NBOMe-LSD might work out
 
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