I Like to Draw Pictures of Random Molecules

[tweex]

Methortetamine (aka 2-Methylmethamphetamine or 2-MMA)

Found a couple papers talking about it from an analytic chem perspective, nothing on pharmacology. A more powerful version of ortetamine?

2-Methyldimethylamphetamine (sup dawg, we herd u liek meth, so we put two more meths on your meth so you can methmeth while you meth)

No info on it anywhere, but I'd think this is a workable structure? I designed it as a hybrid of ortetamine and dimethylamphetamine, keeping in mind both of their relative properties to regular methamphetamine. Possible properties as a fairly nontoxic (albeit likely low potency by weight) functional stim?

Edit: I also wonder about perhaps 2-Fluorodimethylamphetamine (2-FDMA)
Following in the series of 2-FA and 2-FMA... actually this is 2503 in PiHKAL

 

[ebola?]

2-Methyldimethylamphetamine (sup dawg, we herd u liek meth, so we put two more meths on your meth so you can methmeth while you meth)

No info on it anywhere, but I'd think this is a workable structure?

The potency drop from n-dimethylation is too great.

Methortetamine (aka 2-Methylmethamphetamine or 2-MMA)

Maybe more serotonergic? 2-methylation of amps is relatively under-explored. It could be neurotoxically serotonergic.

ebola

 

[tweex]

The potency drop from n-dimethylation is too great.

Do you think the issue with potency would be so great as to be non-bioactive, or simply require much higher dosing for decent effects?

Struck me as an interesting idea for more "clean"/safer meth analogs, even if you'd have to take a lot...

By contrast, equivalent doses of methamphetamine depleted serotonin in the rat brain by 82%. These results indicate that N,N-DMA, the N-methylated analog of methamphetamine, is considerably less potent than its parent compound both as a dopaminergic and serotonergic neurotoxin, and raise the question of whether or not it may be possible to dissociate the neurotoxic effects of methamphetamine from its reinforcing actions by means of N-methylation. Safety of N,N-DMA in humans remains to be investigated.

http://www.sciencedirect.com/science/article/pii/0006899389902473

Methylation in the ortho position of amphetamine on the other hand apparently results in about a 90% potency drop, but similar effects:
https://www.ncbi.nlm.nih.gov/pubmed/2093186

Edit: Whoa, this is a cool read: http://bitnest.ca/Silo42/Books/AmphetamineAndItsAnalogs3.pdf
In relation to these couple compounds, Nichol's claims n-dimethyl is 80% less potent, and that ortho-methylation is 90% less potent but the only ring position that retains classical stim properties. Really cool stuff

 

[sekio]

.
Do you think the issue with potency would be so great as to be non-bioactive, or simply require much higher dosing for decent effects?

I think when you turn to N,N-dialkylamphetamines or their cathinone counterparts, they are more like prodrugs for the N-monoalkyl and dealkylated product. Diethylproprion (N,N-diethylcathinone) is that way; people consider it to be more of a prodrug for ethcathinone. I think the exception are small cyclic N-alkyl groups like pyrrolidine though, which actually work to increase potency somewhat. (c.f. MDPPP versus methylone)

 

[klfiend]

a potency bump from a-pvp?

 

[ebola?]

probably works, maybe a bit more potent, probably feels horrid.

ebola

 

[mad_scientist]

^^^

This is a known compound with code number O-2390, CAS# 850352-61-3

 

[bloodshed344]

5-meo-lsd and 6-fluoro-lsd

So just a quick idea I had when thinking about LSD's relation to tryptamines:

"5-Meo"-LSD

"6-Fluoro"-LSD

Fluorotenin (5-trifluoromethyl-DMT or 5-methylfluoro-DMT)

Psulfurcin (4-Methylthio-DMT (I know this is much different than 4-hydroxy) could anyone answer the question if a sulfonyl would be possible here and if it would be similar to acetyl or phosphoryloxy)

 

[SeenSoFar]

You have mixed up the 4- and 5- positions in your final 2 drawings. The compound you have titled 'Fluorotenin' you have actually drawn as 4-Trifluoromethyl-DMT, and the compound you called Psulfercin you have actually drawn as 5-Methylthio-DMT. As an interesting note, while I have never heard of 4-MeS-DMT (what you meant to draw), 5-MeS-DMT (what you actually drew) was made and assayed by Shulgin, its #46 in the index of TiHKAL. The dose is given as 15-30mg and the duration as less than 1 hour.

 

[bloodshed344]

You have mixed up the 4- and 5- positions in your final 2 drawings. The compound you have titled 'Fluorotenin' you have actually drawn as 4-Trifluoromethyl-DMT, and the compound you called Psulfercin you have actually drawn as 5-Methylthio-DMT. As an interesting note, while I have never heard of 4-MeS-DMT (what you meant to draw), 5-MeS-DMT (what you actually drew) was made and assayed by Shulgin, its #46 in the index of TiHKAL. The dose is given as 15-30mg and the duration as less than 1 hour.

Thank you! I'm too lazy to redraw but I meant them the way they were said, not drawn. I knew about 5-MeS-DMT and it seemed kind of a dud. Judging by 4-MeO-DMT I don't think psulfurcin would be any good but who knows...

 

[SeenSoFar]

Thank you! I'm too lazy to redraw but I meant them the way they were said, not drawn. I knew about 5-MeS-DMT and it seemed kind of a dud. Judging by 4-MeO-DMT I don't think psulfurcin would be any good but who knows...

Its not as clear-cut as you might think. Consider 2,4,5-TrimethoxyPEA vs 2,5-Dimethoxy-4-Methylthio-PEA, also known as 2C-T. TMPEA is not known to be active at any dose, whereas we all know how active 2C-T is. It might not be a perfect example, seeing as it involves PEAs as opposed to tryptamines, but it is a useful parallel. I would actually think that 4-HS-DMT is a better idea though.

 

[atara]

Ew, thiols. A stench that will make AMT seem like a flower garden.

 

[bloodshed344]

4-HS-DMT would have been the actual psulfurcin if I had realized that a hydrosulfur group was possible! What's the real name of this group?

Also, what about a 4-Sulfonyl-DMT?

 

[SeenSoFar]

That group would be a thiol group, analogous to an alcohol group with a sulfur replacing the oxygen. The thio- prefix is used when an oxygen has been swapped out for a sulfur.

As for a sulfonyl group, it seems like an odd choice. It seems like a sulfate ester of psilocin or a sulfate thioester of 4-HS-DMT would be more logical. I am getting the idea that this is what you actually meant when you said 4-Sulfonyl-DMT. Was it? Or did you actually mean sulfonic esters?

 

[bloodshed344]

That group would be a thiol group, analogous to an alcohol group with a sulfur replacing the oxygen. The thio- prefix is used when an oxygen has been swapped out for a sulfur.

As for a sulfonyl group, it seems like an odd choice. It seems like a sulfate ester of psilocin or a sulfate thioester of 4-HS-DMT would be more logical. I am getting the idea that this is what you actually meant when you said 4-Sulfonyl-DMT. Was it? Or did you actually mean sulfonic esters?

I'll have to look it up again, I could easily be getting sulfonyl confused with sulfate or sulfonic... confusing! I looked all 3 of those up and while I know what they are I still don't know which one I intended. What would a sulfate ester or sulfate thioester be, exactly, of 4-HS-DMT? Would it be to 4-HS-DMT as 4-AcO-DMT is to Psilocin? Interesting stuff. Thanks for your help so far.

 

[Transform]

Is there any precedent for ring substitution of LSD, ala the 5-MeO suggested there.

 

[SeenSoFar]

I'll have to look it up again, I could easily be getting sulfonyl confused with sulfate or sulfonic... confusing! I looked all 3 of those up and while I know what they are I still don't know which one I intended. What would a sulfate ester or sulfate thioester be, exactly, of 4-HS-DMT? Would it be to 4-HS-DMT as 4-AcO-DMT is to Psilocin? Interesting stuff. Thanks for your help so far.

A sulfate ester of psilocin would be a logical choice considering the activity of the phosphate ester (4-PO-DMT a.k.a. psilocybin) and the acetate ester (4-AcO-DMT) and would be analogous to either of them, just another ester of psilocin that may be cleaved to form psilocin in vivo, functioning as a prodrug for psilocin as has been the commonly accepted theory regarding the activity of 4-PO-DMT and 4-AcO-DMT. Its also possible it may have activity of its own as is now being theorised about 4-AcO-DMT and 4-PO-DMT. It might be a combination of these as well, with a portion hydrolysing to form the parent phenol and a portion remaining intact, with the effect profile being a result of both substances simultaneously. The sulfate thioester of 4-HS-DMT would be exactly analogous to the sulfate ester of psilocin. A thioester just means an ester formed with an HS (thiol) group instead of an HO (alcohol) group. And a sulfonic ester just means an ester formed by an alcohol and a sulfonyl group. Sulfonic ester is just the correct way of saying sulfonyl ester.

I see no immediate reason why a sulfonic ester would be unwise, its just a slightly less obvious choice compared to a sulfate ester. That's why I asked.

Is there any precedent for ring substitution of LSD, ala the 5-MeO suggested there.

The thought has definitely crossed my mind before, as I'm sure it has crossed many others, but I don't believe that such compounds have ever been synthesized. If they have, I've not heard of them. It seems like a logical step to take for sure, considering how fertile the ground seems to be in tryptamine chemistry. Then again, lysergamides do not behave exactly like tryptamines, so we will just have to see... Make 'em and taste 'em! Such a shame the 4- position is occupied, the thought of 4-HO-LSD makes me need to change my undergarments.

 

[bloodshed344]

A sulfate ester of psilocin would be a logical choice considering the activity of the phosphate ester (4-PO-DMT a.k.a. psilocybin) and the acetate ester (4-AcO-DMT) and would be analogous to either of them, just another ester of psilocin that may be cleaved to form psilocin in vivo, functioning as a prodrug for psilocin as has been the commonly accepted theory regarding the activity of 4-PO-DMT and 4-AcO-DMT. Its also possible it may have activity of its own as is now being theorised about 4-AcO-DMT and 4-PO-DMT. It might be a combination of these as well, with a portion hydrolysing to form the parent phenol and a portion remaining intact, with the effect profile being a result of both substances simultaneously. The sulfate thioester of 4-HS-DMT would be exactly analogous to the sulfate ester of psilocin. A thioester just means an ester formed with an HS (thiol) group instead of an HO (alcohol) group. And a sulfonic ester just means an ester formed by an alcohol and a sulfonyl group. Sulfonic ester is just the correct way of saying sulfonyl ester.

I see no immediate reason why a sulfonic ester would be unwise, its just a slightly less obvious choice compared to a sulfate ester. That's why I asked.



The thought has definitely crossed my mind before, as I'm sure it has crossed many others, but I don't believe that such compounds have ever been synthesized. If they have, I've not heard of them. It seems like a logical step to take for sure, considering how fertile the ground seems to be in tryptamine chemistry. Then again, lysergamides do not behave exactly like tryptamines, so we will just have to see... Make 'em and taste 'em! Such a shame the 4- position is occupied, the thought of 4-HO-LSD makes me need to change my undergarments.

I think replacing LSD's phenyl or indol rings with a thiophene or benzofuran ring would be a next logical step, considering I've seen a version of DMT with the indol replaced with thiophene and a version of DMT with the phenyl replaced with thiophene. Crazy chemistry but I guess it'd be about 100x harder to do with LSD. I think light substituents on the phenyl ring could lead to good analogs, that was my point with 6-Fluoro-LSD, to create something that would maybe be similar to LSD... but there's a low chance of that being true.

 

[SeenSoFar]

I think replacing LSD's phenyl or Indol rings with a thiophene or benzofuran ring would be a next logical step, considering I've seen a version of DMT with the indol replaced with thiophene and a version of DMT with the phenyl replaced with thiophene. Crazy chemistry but I guess it'd be about 100x harder to do with LSD. I think light substituents on the phenyl ring could lead to good analogs, that was my point with 6-Fluoro-LSD, to create something that would maybe be similar to LSD... but there's a low chance of that being true.

So you know, indole describes the combination of the 5- and 6- membered rings, if you want to refer to just the 5- membered ring, its called a pyrrole ring. Anyway, the thienopyrrole analogue of DMT (with the thiophene ring replacing the benzene ring) does bind to 5-HT2_A, however it is inactive as a hallucinogen^[1]. On the other hand, the benzothiophene analogue (with the thiophene ring replacing the pyrrole ring) is around (CAS#:10275-64-6) and has been reported to be a hallucinogen (at about half the potency of DMT) on Bluelight^[2] and other anecdotal sources but I don't believe its binding efficacy has ever been formally assayed. If anyone knows otherwise, please chime in! The benzofuran analogue of 5-MeO-DMT^[3] has been discussed on Bluelight^[4], check out the discussion there for some interesting facts and back-and-forth.

While this is interesting information and might make a very interesting avenue of exploration in the future as far as analogues of known tryptamines (I know I would be interested in assaying benzothiophene aMT analogues), ergoloid chemistry is a whole 'nother ball-game. Ring substitutions are one thing, and I can think of a few ways they could be accomplished without TOO much trouble, but replacing either of the rings in the base indole of LSD is a HUGE proposition. Whereas with the former you can still start with the same precursors as you would with LSD, for the latter you are looking at a total synthesis, and that is not a small job. You're looking at huge costs, lots of work, and a small yield. While it would definitely be an interesting avenue to explore, especially the benzothiophene analogues, I just don't see it happening unfortunately... The simple ring substitutions are something I definitely would like to see happen though.

[1] - http://www.ncbi.nlm.nih.gov/m/pubmed/10090793/

[2] - http://www.bluelight.ru/vb/threads/344768-Other-aromatic-analogues-of-PHE-and-T

[3] - http://en.m.wikipedia.org/wiki/Dimemebfe

[4] - http://www.bluelight.ru/vb/threads/592648-Benzofuran-analogues-of-Tryptamines-(e-g-5-MeO-BFE)

 

[toastmann]

Im interested what 6-trifluoro-aMT would feel like.
But let's first see reports of 5/6-fluoro-aMT. I wonder why it hasn't been synthesized on a large scale. I mean they are strong MAO-A inhibitors but I have seen more dangerous chemicals pop up so that shouldn't be a problem.