• Neuroscience & Pharmacology Discussion Welcome Guest
    Posting Rules Bluelight Rules
    Recent Journal Articles Chemistry Mega-Thread
    FREE Chemistry Databases! Self-Education Guide

  • N&PD Moderators: Skorpio | someguyontheinternet

Indolethyl-dimethylazetidine

Morninggloryseed

Morninggloryseed

Bluelight Crew
Joined
Aug 22, 2000
Messages
13,772
Location
Semi Retired
I’m very surprised that I’ve not seen this anywhere. Since the “azetidine” analogue of LSD is known, and of extreme potency…why has no one thought to incoperate this into a tryptamine structure? I know of other IEA’s that end in rings and retain activity. Since this worked on LSD (where usually any change abolishes activity), I see no reason for it not to work here. It is easy to see DiPT, EIPT, and other N,N-dialkyltryptamines in this new structure. “Azetitryptamine”

What do you brains think of this one?
 

Attachments

  • az_tryp_ana.JPG
    az_tryp_ana.JPG
    18.6 KB · Views: 246
Ooooh, interesting. Is this actually possible to synth? It looks rather "forced" to me.. though as you all know I suffer from foot-in-mouth disease when it comes to chemistry ;).

I suppose a the most we know of is distantly-close (erm..) relative to this, shape-wise, that being Pyr-T, no? The latter doesnt seem friendly...
 
Isn't that the wrong nitrogen to put it on? If you overlay the structure of tryptamine onto LSD the "amine" nitrogen is the one at the 6 position, not the one from the "diethylamide".

This structure would be good to put onto a tryptamine or PEA but it should be at the end of an alkyl chain attached to the amine nitrogen...um not sure how to name the azetidine, but the LSD pattern would make N-methyl-N-(gamma-diethylamidopropyl)tryptamine
 
morninggloryseed said:
I’m very surprised that I’ve not seen this anywhere. Since the “azetidine” analogue of LSD is known, and of extreme potency…why has no one thought to incoperate this into a tryptamine structure? I know of other IEA’s that end in rings and retain activity. Since this worked on LSD (where usually any change abolishes activity), I see no reason for it not to work here. It is easy to see DiPT, EIPT, and other N,N-dialkyltryptamines in this new structure. “Azetitryptamine”

What do you brains think of this one?
Click to expand...

I would expect nichols has synthesised this one already as in his azetidine LSD paper he refers to the possibility of the dimethylazetidine moety replacing diethylamine in other drugs. the obvious one is DET. there are several possible isomers of this compound wich would be interesting to assay to probe that area of the receptor.
related compounds the 2-N-methylpyrrolidine analogs have been made and tasted, these are the ones made from proline by nichols and apparently are nothing special roughly the same activity as DET orally, the 1-pyrolllidyl and 1 piperidyl are the pip and pyr T of tihkal are really not nice, though they have appeared as RC's,
the azetidines should be possible to synthesise, indeed it may be possible to synthesise the dimethyl aziridine which is even closer to DET in size, Nichols was unable to synthesise the dimethyl aziridine analog of LSD but the dimethylaziridinyl indolethylamine woud use a much different route.
 
You are correct, this corresponds to LSD's nitrogen at the 6, not the amide. Obviously, that was not the N I meant. My comparison with the azetidine analogue of LSD was simply to say such a substitution can be done on a molecule where N-alkyl groups play an important role, and still retain activity.

mad_scientist said:
Isn't that the wrong nitrogen to put it on? If you overlay the structure of tryptamine onto LSD the "amine" nitrogen is the one at the 6 position, not the one from the "diethylamide".

This structure would be good to put onto a tryptamine or PEA but it should be at the end of an alkyl chain attached to the amine nitrogen...um not sure how to name the azetidine, but the LSD pattern would make N-methyl-N-(gamma-diethylamidopropyl)tryptamine
Click to expand...
 
Last edited:
morninggloryseed said:
You are correct, this corresponds to LSD's nitrogen at the 6, not the amide. Obviously, that was not the N I meant. My comparison with the azetidine analogue of LSD was simply to say such a substitution can be done on a molecule where N-alkyl groups play an important role, and still retain activity.
Click to expand...

despite the fact you can overlay the two structures and this idea was first postulated 40 plus years ago there is little or no conclusive evidence that the terminal nitrogen in a tryptamine or a phenethylamine corresponds with the 6 nitrogen of LSD. it is quite possble for tryptamines or phenethylamines to bind in a different way to LSD and still activate the receptor.
 
^Thats what I was trying to pose when I revamped the Dragonflies, 5ht2... thread
F&B's model has the terminal at the 6

If Nichols has really made these and they are on a similar potency level to DET, then I think that is a strong argument for the nonconventional overlay of the TEA structure over the ergoloid structure, ie, the indole N on TEAs corresponding to the 6 ergoloid N.

In about 6 months I will be undertaking a project to thoroughly evaluate a neurotransmitter model and hope to use the 5-ht2 relationships as the basis of my project.

MGS-I thought the azetidine moiety was on the amide N?
 
the azetidines should be possible to synthesise, indeed it may be possible to synthesise the dimethyl aziridine which is even closer to DET in size, Nichols was unable to synthesise the dimethyl aziridine analog of LSD but the dimethylaziridinyl indolethylamine woud use a much different route.
Click to expand...

Anybody here want to put an aziridine into your body? I for one wouldn't even consider it as any aziridine you want to consider has got a hideous toxicology profile (the ring opens very easily and acts as an alkylator). 2-phenyl-1,3-dimethylaziridine kills people - it's a good bet the IEA versions will do as well.


I would expect nichols has synthesised this one already as in his azetidine LSD paper he refers to the possibility of the dimethylazetidine moety replacing diethylamine in other drugs
Click to expand...

That's why I'm sticking with the model of how they interact with the receptor in 'acid, dragonflies etc'. It's all conjecture and possibility with no proof. The diethylamide functional group is very, very different to the 6-position amine group. With the diethylamide, the structure the two ethyl groups take are not the lowest energy conformation, which is demonstrated by the activity by the dimethylazetidine amide. The stereochemistry of the 6-position amine group of d-LSD is the same as the more active isomers of the optically active tryptamines & phenethylamines. If the diethylamine structure was in any way special for the 6-position/side chain nitrogen for ergolines/tryptamines, then DET would be markedly different to the dimethyl and other substitution patterns (as would the ring substituted derivatives), and it's not.

If Nichols has really made these and they are on a similar potency level to DET, then I think that is a strong argument for the nonconventional overlay of the TEA structure over the ergoloid structure, ie, the indole N on TEAs corresponding to the 6 ergoloid N.
Click to expand...

No, for that to be the case, the diethylamine derivatives would have to be almost a n order of magnitude more potent than the DMT etc derivatives, as happens with LSD (as mentioned previously, they're not).

The case for the model proposed in Acid, dragonflies etc is much, much stronger than for the non-conventional overlay. There are other properties of the compounds that back this model. If required I'll trot them out to illustrate
 
fastandbulbous said:
With the diethylamide, the structure the two ethyl groups take are not the lowest energy conformation, which is demonstrated by the activity by the dimethylazetidine amide.
Click to expand...

I don't follow you here but would like to know more...

If the diethylamine structure was in any way special for the 6-position/side chain nitrogen for ergolines/tryptamines, then DET would be markedly different to the dimethyl and other substitution patterns (as would the ring substituted derivatives), and it's not.
Click to expand...

except that it is orally active at much lower doses than the propyl and methyl derivatives...only 2x for the propyl, but much, much higher than the methyl. not an order of magnitude for the propyl, but a start. the isopropyl is the only homo-substituted derivative that is of similar potency orally, but we know the can of worms that bugger is. is there a paper that lists the potencies in a nice chart fashion for the lysergamides?


The case for the model proposed in Acid, dragonflies etc is much, much stronger than for the non-conventional overlay. There are other properties of the compounds that back this model. If required I'll trot them out to illustrate
Click to expand...

/gets a vision of f&b's dog-like mountain of references ready to pounce...
i believe it is non-conventional in some fashion but am honestly too caught up in other work, yet eagerly anticipating the chance to sink my teeth into it for real and we can give it a go again :)
 
The most interesting thing on this molecule with its possible particular overlay of DIPT will be if its as well active as an auditory distorter like DIPT.There has yet to be Another molecule doing that,sort of declaration of bankruptcy by the chemists ...
 
fastandbulbous said:
Anybody here want to put an aziridine into your body? I for one wouldn't even consider it as any aziridine you want to consider has got a hideous toxicology profile (the ring opens very easily and acts as an alkylator). 2-phenyl-1,3-dimethylaziridine kills people - it's a good bet the IEA versions will do as well.
Click to expand...
very good point, perhaps is the answer, if it didn't self destruct during the synthesis I am thinking of then it isn't that reactive and therefore not that dangerous. btw i am not planning on the synthesis of this.
just in terms of basic the 1 arylalkyl aziridines appear more stable than the 2 arylalkyl and 2 aryl aziridines. the aryl group activates the aziridine.
 
hugo24 said:
The most interesting thing on this molecule with its possible particular overlay of DIPT will be if its as well active as an auditory distorter like DIPT.There has yet to be Another molecule doing that,sort of declaration of bankruptcy by the chemists ...
Click to expand...
I think it has to do with a hydrophobic region somewhere extended out linearly from the 2-3 position, though I have no idea why DPT wouldn't have much of an effect.. I'd bet it just binds to some 5HT2A like serotonergic receptor we've yet to map out near the ears or in the temporal lobe.

the azetidine analogue looks difficult and expensive to make and potentially hazardous
 
I've actually come across the azetidine analogs of some compounds and they were actually pretty damned stable. I agree that they would cost a fortune to make, but it's handy to be able to make another 3 isomers of your diethyl compounds, just to look at what is happening to the receptor profile. I would think that the LDS analogs are the only ones where extreme potency outweighs the costs. You can make the 2,4 dimethyl azetidine from acetyl acetone (I know, thats the OLD name). Reduce, make halide, form ring. Optical seperation is MORE of a bitch!
 
f&b,

Are you saying that starting with either 4-OH-3-indolyl-(C=O)-(C=O)-Cl or plain
3-indolyl-(C=O)-(C=O)-Cl plus NH(cyclic(CH2)2) followed by reduction of the di carbonyls with anhydrous lithium aluminium hydride LiAlH4 (a hydride is an H-) under dry Ar aka Argon or He aka Helium in diethyl ether CH3CH2-O-CH2CH3 you would get one of two deadly compounds?
no es (con'td) muy f&b.
u-los-o. veritadidas? puma? fila? nike? quales son suse's shudras?quien(es) se puede(n) saber la futura en a(d)vencia? je suis une homme yo. mtv raps.
on wood. wood spirits. destructive distillation. perfumery.
the essence of the essenes. the spirit molecule with one more sigma bond. sigma aldrich. bell laboratories. dexter's laboratory.

pinnacle rex apex nadir analemma pit pendulum dandelion punctuation pleasure ejaculation whilst pondering equatorial sphereradial sidereal surrealism in a stuporious retrograde amnesiac inducing state of semi quasi retardation known as brahmanic consciousness expanding exploring andadamide like stupefaction of sensory distortion to evokate widespread spectacular magnifacation of ananda, eternality beyond all tiempo, life expanding copulation of sanctity and yellow glow sticks and true knosis approaching infinity while changing from 4th to 5th gear going 112 mph on Interstate 19 and waving hello to concurrent concomitant conspicuous cotravelers of time space and making wrought the best most impossible unpredictable solution to what ails every sentient being on the planet earth gaia and beyond w/o having to pretend to fly to and walk on the moon of diana princess di sam felicia orion the waters of the deep azure oceans of planet indigo lejos through psychedelic quasi legal drug self experimentation yoga (yoga does not have to be aerobics, that's just silly!; did yr yoga HW and u would kno that yoga means literally to yoke or bring together or have sex with the divine in an ecstatic epiphinanous spurtatious climactic crystal clear alliteration in pure white or maybe butter yellow soft light of amore dioscidaddic manifesting trip roll joint pipe paraclassicologistical tacit orgasm in another dimension with a power higher than yourself beyond label beyond measurement beyond reproach beyond the zen of the cynic beyond the virtually meaningless word choice ('diction') incomphrehensible inelegant vocabulary or sophistry of the biochemist trying to do organic chemistry advancements wrt psychopsychedelic innovation of the 3rd kind crapb. not being flippant, just mean. baseheadz. bassheadz. communism. near now ineluctable pandemicalchimeric monetary fiscal policy collapse due to out of control war boondoggle google it! federal state county and or parish overexpendition of liquidity forbidden usury credit cards low pay for entrylevel positions overpriced colleges and unis that aren't even free much less all that useuful and, mainly, widespread depopulation of major cities on domestic soil using nuclear explonation devices etc.

seminiferous tubules' meiotic progeny cum flagellates?

moreover u ademas in otras words if you took off the dimethyls off would the product still be a toxic alkylator of mankind? i somehow doubt it. Tesla. Space Invader Aliens on Grass. zombienation. reincarnation. prana purusha rita. samsara. sam's club.

Azetidine azidirine [4-OH] tryptamine: so whaddaya get prollyo?
!!Pues metinks probably 2 more 'wyrd asz drogenzs' of the N-cyclo-CH-ed ethylene [here -CH2CH2-; see also arabic numberal 7; July] beta 3-indole class kind or type. x:x:y!@...
Sincerely, the beatific neolonalaknonuddinonu.
eloleneocimbolologoslinguaeknosisuniversaleyoperadoraqui.
Como puedo ayudarvosotrosudstes hoydia y beyonce?
Los 4 cardinals.
The fixed signs of the ecliptic.
The homosapienackercracker!
Tu necesitas eros galore.
Yo doy significance donde antes de there was solo strifa.
me invento ideas plentifallmentos prolificos sin duda dawgs!

Es una blatante verdida factoid that y = sine x trigonometric 2D Cartesian coordinate system ist the sinusoidal curve de Shroedinger por un solo ejamplo.
Logosorrheal orchidial iatrogenetic ititis inducing not pendantic poetic peripatic l orchardidatic aural coded masturbatory verbal non action of the silent/unspoken type. Netwerking optimatically ('action at a distance') se require connectiones buenas diverse ubiquitous y polyerotical philosophical self-starter ismishistic realities y realities. Yo tengo mas colores than une peecock yoyoboiszeez! j/not/k.

transcendal free base free bass exhalation of local herbal isolated from anesthetic and imported then ignited in air by internal bionic alveolic exchange resin incantation prolongation excitation jubilation alkaloid of the bicyclotype and originator of much of the world's economic wealth along with coffee tobacco sugar cane wheat corn soybeans alfalfa the lone ranger zoro and bugs bunny crossed with the black panther who doesn't pensee that the color pink corresponds to punkdaffatry very well quackers. Quaker oatmeal. Chelsea Clinton's high school.
Stanford stadium. The palladium. Pallid. Anemia of the real kind due to ferrous concentration imbalation out of whacker oxidation reductive secondary amine compound mdp2p & CH3NH2 alylation. The domain of which smells like licorice and cat piss. Territorial demarcation. Adept artful communication. Multipolynimous alliteration and electric alternating currents si chips. Worldwide computer camera information coup d'etation? Miscalculation. No calculation. Conspiracy to entrain with electromagnetic airwave amplification of amplitude certain federal communications communication controlled wavelengths of the spectrum to lull worker humans into concupiscent complancency and unconscious stupefication. The Silence of the Lambs. Vermillion. Vermutton. Lamb chops. Veal. Dangerous Minds. Alexander Pope. Quiptations of adagogic adaptations of truthianisms made currently apt and not irrevelant based on literary ability and dry sardonic wit and wisdom. The Tao de Ching by Lao Tzu. The Bhagavad Gita.
The Summers of Love. The Winter of Our Discontent. The Spring of Intensity.

Prolific pervasive global proliferation of purported annihilation of pretended ignoramical worldwide religio philosophical mythologico comparative body of knowlegde of god type hermaphroditicidt ie mutability and elasticity. The pd point where y=sin x or cos x and y=0 [sine and cose are equivalent if phase shift of domain parameters is initiated]; a node. A nodule. An i-pod. Lila. Lula.
Mary Jane and Juan. Speedee Gonzales.
 
Last edited:
right ^ lol

i've been reading this for a while and this fool come on and starts to rant in tard-mode..

continue smart people :)
 
You must log in or register to reply here.
Top