Phenethylamines as tryptamine analogues

[Dr.Heckyll]

Here's the answer to your question:

I'm really curious as to whether 3-(2-dimethylaminoethyl)benzofuran and 5-methoxy-3-(2-dimethylaminoethyl)benzofuran are active compounds, as the onlt change between them and DMT/5-methoxyDMT is the replacement of the indolic nitrogen with an oxygen atom, which, as the dragonflies have shown, is quite capable of replacing the hydrogen bonding function of the indolic nitrogen

J Med Chem. 1992 May 29;35(11):2061-4.
Benzofuran bioisosteres of hallucinogenic tryptamines.Tomaszewski Z, Johnson MP, Huang X, Nichols DE.
Department of Medicinal Chemistry, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907.

The benzofuran analogues of the hallucinogens 5-methoxy-N,N-dimethyltryptamine and 5-methoxy-alpha-methyltryptamine were synthesized and evaluated for affinity at the serotonin 5-HT2 and 5-HT1A receptors in rat brain homogenate, labeled with [125I]-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane ([125I]DOI) and [3H]-8-hydroxy-2-(N,N-di-n-propylamino)tetralin ([3H]-8-OH-DPAT), respectively. At the 5-HT2 receptor, the benzofurans had slightly decreased affinities, approximately one-third and one-sixth those of the indoles, for the primary amines and the tertiary amines, respectively. The benzofurans also had lower affinity at the 5-HT1A receptor, but decreased only about 20-30% from that of the indole isosteres. Thus, the 5-HT1A receptor is less discriminating with respect to preference for an indole versus a benzofuran, although all of the compounds did have higher affinities for the 5-HT2 receptor than for the 5-HT1A receptor. It is suggested that benzofurans may be useful in the design of serotonin receptor ligands.

PMID: 1534585

 

[fastandbulbous]

Hey, what happened to the pics in this thread?

Sorry, they were in my gallery and had to be removed under the new restrictions of 15 pics per member. I'm currently in the process of housing them at another place & when that's done I'll tinker with the original posts so the pictures reappear

As to the benzofurans, I'm sure I'd read somewhere that they had higher affinities than that, but my memory isn't what it used to be. I'm pretty certain ir wouldn't be the sulphur analogues as then you've got size as well as lone pair differences to a nitrogen atom.

While it seems to rule out some of the benzofuran tertiary amine tryptamines (one sixth the affinity of DMT implies a dosage of 360mg for the benzofuran), although the benzofuran analogue of psilocin would be active (if there's no weird metabolic effect to consider) at the 60mg mark and would be perfectly legal (in the UK at keast), the primary amines seem a better bet. Nobody would want a 5-methoxyAMT analogue (at least no one in their right mind!), but the benzofuran analogue of AMT should be actoive at 60mg (if 1/3rd potency and AMT active at 20mg), which is well worth bothering with

 

[5-HT2]

I remember hearing from at least one reputable source (perhaps from Nichols himself when I met him at Mind States '03) that the butterfly phenethylamines are likely to be hepatotoxic because of the furans, and that removing the double bond and turning them into the dragonflies reduces the putative toxicity. Would this also be likely for any tryptamines with benzofuran functionality?

 

[vecktor]

toxic benzofurans

I remember hearing from at least one reputable source (perhaps from Nichols himself when I met him at Mind States '03) that the butterfly phenethylamines are likely to be hepatotoxic because of the furans, and that removing the double bond and turning them into the dragonflies reduces the putative toxicity. Would this also be likely for any tryptamines with benzofuran functionality?

my understanding is that there has to be a side chain attached to the furan part of the benzofuran for hapatotoxicity.
Don't quote me on that.

 

[nuke]

Will that cover things like, the difference between AcO and HO (acetoxy and hydroxy?) (just a simple example), other naming stuff? what isomer means, different examples of this and such. stuff along those lines. I want to read and understand these books, I don't actualy want to go out and create the stuff, interested in whats going on inside my head and how it gets there more than anything, I want to be more educated in my quest into the research chems world.

I'll try find above mentioned book in the library and see for my self I guess, although a bit more verbose discussion with some options would be great, eh here I am thread hijacking again!

It'll teach you all the basics, yeah. It goes above and beyond that into synthesis/reactions and all, too.

As for benzodifuran toxicity: I've tried 2c-b-fly a few times and my liver enzymes have been normal since. I don't think there's much of a concern..

And it seems Vecktor is right:

From http://pages.unibas.ch/diss/2005/DissB_7162.pdf :
"We conclude that benzarone, benzbromarone as well as amiodarone are toxic to isolated rat liver mitochondria as well as to whole hepatocytes. The benzofuran structure alone is not responsible for the hepatotoxic effects, sidechains at the furan ring are necessary. Hepatic injury associated with the ingestion of these drugs can be explained by mitochondrial damage with subsequent induction of apoptosis and necrosis."

 

[yoyoman]

^^

you can host images real fast & easy at http://imageshack.us

 

[Helios.]

It boils down to either 5-HT and/or DA mimickry.
The pharmacophore of DA can even be found in morphine.

 

[nelix]

This has been one of the most interesting threads I have read on BL (not to down play some others!).
I wish I was smart enough to get involved *hits the books*

 

[ungelesene_bettlek]

very interesting thread! unfortunately, the pictures of the initial post are gone in the meantime. can you please reupload them, fastandbulbous? or anyone else who happens to still have them?

 

[Dude Man]

yeah checked the links and no pics available. very intersted in where this was headed as well. was this just speculation before the explaination of hemiflies popped up, is this what lead to that info coming up on wikipedia on such,

THE FOLLOWING IS A SIDE TANGENT TO FASTANDBULBOUS (OUR RECENTLY RETIRED MODERATOR. WILL PM IT TO HIM. NODDING OFF AND SHIT SO PLEASE MODS IF GOING TO DELET THIS GIVE ME AT LEAST 2 HOURS FOR THE SMACK TO WEAR OFF SO CAN SEND A PM.; LEAVING THIS PAGE CAUSING ME PROBLEMS. IT IS NOW ABOUT 3 AM CENTRAL TIME SO PLEASE WAIT TILL LIKE FIVE AM OR SO STANDARD TIME US BELIEVE -6 FROM THE MAIN TIME PKLACE.
many unaswered questions that shall prob remain so with the retirement of f&B...(we will miss you and you extremly insightful knowldge buddy. i wish you the best on all of you future endevors. just remeber hoe many people you have helped and hhow many lives you have probally saved through harme reduction even on the things like simple dosages [image if someone like you wasnt around and some moderator half assed an answer to bromo dragon fly and said good dose shou be i guess 3-4 mg. you personally probally honest;y saved lives in situations like that bro. like i said hopefully someday you will be back but what ever is important to you is all that is important in your life and it is your life and more so your responsibility to fulfil your life over anything else even this harm reduction site cause what good is giving advance and talking and researching drugs do if you find yoiu are not enjoying it enough any more to make it worth the effect on your personal life...only yu can determine when and where to draw the line and it takes alot when so emersed in any culture or activity especailly one you has such a epic pasion for but you did it and hopefully its working out. and if you so choose i hope you come back to us. if not hopefully you find fulfillment in all your future endevors.