Thiaminorex Sexual Aphrodisiac Stimulant..Safer Alternative to Aminorex?

[fastandbulbous]

Thinking about the metabolic fate of that ring made me very worried. However, it appears that 2-aminothiazolines occur in the human body:

2-Aminothiazoline-4-carboxylic acid - Wikipedia

en.wikipedia.org

So this may not be so dangerous at least in that way.

Anyway, aminorex is reported to be a monoamine oxidase inhibitor! Unfortunately replacing O by S usually doesn't affect this activity; cf. PMA and 4-MTA. So I'm skeptical of the safety anyway.

On the other hand N-ethylaminorex might be worth looking into. Ethyl isocyanate is a pretty nasty reagent, though!

I wouldn't feel so confident over swapping a sulphur atom for an oxygen. 2,4,5-trimethoxyphenethyl amine is ineffective unless a MAOI is administered at the same time. On the other hand, replacing the 4-oxygen atom with sulphur gives 2C-T, which works on its own orally. Equally aleph-1 (DOT) is a much more potent inhibitor of MAO than TMA-2.
My theory is that the replacement of the 4 oxygen with a sulphur, allows the compound to occupy the active site, due to ssimila electronic structure, but the sulphur prevents the enzyme from taking the active conformation, hence a competitive MAO. Think, on it's own, when snorted (rapid onset), proved fatal. As the alkyl group on the sulphur gets bigger, the more potent an MAOI it is.

 

[fastandbulbous]

Above, last paragraph was referencing 2C-T-7

 

[paracelsius]

Oh sorry I did not express myself right, I think you understood it the opposite way now :D

Yes I miss-understood your point. I thought you were talking about desoxy in general compared to other stims, not specifically 4-MAR. But it is hard to compare the 2: the first is a pure dopamine-norepinephrine reuptake inhibitor, the second is dopamine-norepinephrine-serotonine releaser (with somewhat selectivity for dopamine-norepinephrine as I mentioned. But anyway I’d stay away from that one, too much risk of psychosis+unbelievably long half-life (active starting at 0.5mg and can last 5-7days? That’s crazy!

Oh you are talking about that simple version via the N-ureidio-amine?

Yeah that works fine for the 4-unsubstituted version, but also for the N,4-disubstituted version.
Not the 4-monosubbed aminoalcohols!!!
There is a certain board which can be easily found, which concentrates on the topic of harm reduction (=i.e. drug synthesis), we have a thread about that topic on there why this is NOT a suitable alternative.
Complete with ref's.

Right. For the 2-amino oxazolines, thats one way to avoid use of toxic cyanogen bromide, by cyclization of the PPA urea derivative. Surprise the 4-sub didnt work!? But I’ve found another benign and even less toxic reagent that gives you same thing in one step instead of 2. Plus use water as solvent (can’t be safer than that!). Will post details on other forums. Are you talking about r/theehive thread archives?

I would like to try the thiazolamine of 4-MAR still, though, as I can compare that to the oxazoline, but would not use that for extensive bioassays.

My preferable target is 5-phenyl-2-thiazolamine, "thio(a)minorex".
This should be 1. more abuse- and enjoyable, but 2. also safer to use, while 3., also much cheaper to synthesize.

I agree, not only the plain Thiaminorex (5-phenyl-2-aminothiazoline, OP structure) is possibly more fun and less toxic but way easier to synthesize from common cheap unwatched precursors. I’ll post synth details of that one some chemistry forums. Plus I expect the thiazolines analogs to have shorter duration than the oxazolines because the sulfur will most likely get quickly oxidized to inactive S-oxides metabolites and excreted.

As for the thio analog of 4-MAR, I be very cautious about that one. I think it will probably be empathogenic more like MDMA than meth, or even like 4,4’-DMAR. Yeah sure it may be more euphoric than mdma but I’d worry about too much serotonin release and risk of serotonin syndrome with that one. 4-MAR is already 5x more potent at releasing serotonin than mdma. Then again “the poison is in the dose, not the substance”, I forget who said that?

 

[paracelsius]

My theory is that the replacement of the 4 oxygen with a sulphur, allows the compound to occupy the active site, due to ssimila electronic structure, but the sulphur prevents the enzyme from taking the active conformation, hence a competitive MAO. Think, on it's own, when snorted (rapid onset), proved fatal. As the alkyl group on the sulphur gets bigger, the more potent an MAOI it is.

Sure the sulfur homolog may bind to the enzyme same way as the oxygen. But I doubt it will stay long there and inhibit the enzyme. At least when the sulfur is close to the amino group targeted by MAOs. Reason I am staying that is after all, MAOs basically generate HO. free radicals (basically hydrogen peroxide) in the local active site environment of the enzyme and stick it (OH) alfa to the amino. I think under those conditions the sulfur will get instantly oxidized to inactive metabolites.

The closest to OP structure I found is 2-phenylthiomorpholine. It is a weak (pretty much inactive) MAOI, with Ki 100uM, about 10x less active than d-amphetamine which itself is a shitty MAOI. The active dose (going by d-amph EC50) versus the MAO inhibition dose is about 1/1000. That means one would probably be dead long long before the MAO inhibition activity becomes significant!! But who knows?

TO ALL BLIGHTERS: HAPPY NEW YEAR. STAY SAFE.

 

[obviously_not_carl]

I am pretty pissed to find out that both the 4-methyl and unsusbstituted thio analogues are being sold.
They even used the name.

And in the meantime, it had made me sad.
Well at least we might get to hear a bioassay(s) elsewhere from.

Also, you're confusing aminorex and rexamino analoges.
If there is an oxygen on the benzylic positions, or sulfur, its the right one, is there an amine, wrong, then its rexamino with a third of its potency.

 

[paracelsius]

I guess chinese RC vendors are reading BL. Or is it that coming Dutch blanket ban of cathinones making ppl look for aminorex analogs as replacement? anyway if chinese they will probably fuck it up sellin shit contamined with toxic by-products..like that 2-map opioid RC containing cinnamyl chloride/bromide by-product that basically chew people's insides..FCK! I hope not!

No I mean OP type compound (5-phenyl-4-methyl-2-amino not rexamino types (4-Phenyl-5-methyl-2-amino! Those are inactive. Anyway I wouldnt worry too much about MAO. what I worry most is too much serotonin release increase especially with the 4-methyl-5-phenyl thiazoline (thio-MAR). I'd stay away from that one or at least be extra careful!!! Stupid whoever is selling that shit (thio-MAR) without no fcking idea what they doing!!! make me mad!

 

[obviously_not_carl]

Yeah but not from china and no, rexamino's are not inactive.

Also I don't buy drugs, thats for plebs.

 

[plumbus-nine]

Oh, needa find a vendor for these. Unfortunately my known ones only briefly sold 4-[chloro, fluoro, and bromo]-aminorex and I was too late, source got shut down. I understand that you who can synth your own stuff are pissed, for sure, but I can't synth and love aminorexes, at least 4,4'-DMAR was so good. If these derivates are anything like it or what I read over 4-mar, then they are good.

MAOI activity isn't a prob probably as 4,4'-DMAR was one and I even had venlafaxine in my system when trying it, as well as on the day after to counter act the slight serotonin depletion. I know there were deaths but guess they either were susceptible and/or mixed with other, strong releasers.

 

[Xorkoth]

I think the 4[b/c/f]-MAR are still around. But the reports I have read claim them to be decent, but nothing too special. I would have ordered by now but the 5 gram minimum order amount is offputting, I do not need anywhere near that much of a euphoric stimulant on hand.

Wish I could have tried 4,4'-DMAR, or 4-MAR itself, I've always wanted to try 4-MAR since like 2001 when I first read about it. Never encountered it or met anyone in real life who has.

 

[logos_rising]

I know the sulphur is in a different position, but I came across a couple of papers that seems loosely relevant to this discussion and aminorex in general. While it appears that these scientists discovered a novel botanical alkaloid precursor, barbarin, after horses tested positive for aminorex that had not been exposed to levamisole, its not clear to me why they didn't consider another endogenous possibility. For example, phenylethanolamine is an endogenous precursor to aminorex found in the body in trace amounts and the consumption of plants containing cyanogenic compounds might well cyclize it to aminorex in situ. As atara pointed out, 2-aminothiazolines are formed in the body and one route is L-cysteine + cyanogenic compounds as I recall. In any event, I never was able to find out any more information regarding Thiaminorex (5-phenyl-2-aminothiazoline) or whether its even available, but I was excited to see this discussion because it was a molecule I had thought about years ago when pondering the possibility of a safer shorter acting aminorex compound.

Aminorex identified in horse urine following consumption of Barbarea vulgaris; a preliminary report​

Aminorex identified in horse urine following consumption of Barbarea vulgaris; a preliminary report - Irish Veterinary Journal

Background Aminorex, (RS)-5- Phenyl-4,5-dihydro-1,3-oxazol-2-amine, is an amphetamine-like anorectic and in the United States a Drug Enforcement Administration [DEA] Schedule 1 controlled substance. Aminorex in horse urine is usually present as a metabolite of Levamisole, an equine anthelmintic...

link.springer.com

Synthesis and characterization of barbarin, a possible source of unexplained aminorex identifications in forensic science​

https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/full/10.1002/dta.2883

 

[AlsoTapered]

Aminorex exists as a a tautomer and so part of the time the primary amine is responsible for binding, part of the time the secondary amine. I think that is why it's so potent and as soon as you block the para position of the aromatic, it's duration is so dang long. That is what makes it's 3,4-MD derivative so great. Both isomers are active with one being like MDA, the other more like MDMA - so it has the best aspects of both.

70mg of MDAR is as good as 125mg of MDMA.

1 hosted at ImgBB

Image 1 hosted in ImgBB

ibb.co

 

[logos_rising]

Is it the oxazole or oxazoline ring and/or other molecular features that determines whether these thiaminorex derivatives are monoamine releasers/reuptake inhibitors or dopamine autoreceptor agonists?

Substituted 2-aminothiazoles as dopaminergic agents​

EP0345533A1 - Substituted 2-aminothiazoles as dopaminergic agents - Google Patents

Substituted 2-aminothiazoles are described, as well as methods for the preparation and pharmaceutical compositions of same, which are useful as dopamine agonists with selectivity for the presynaptic dopamine receptor and are useful as dopaminergic, antipsychotic, and antihypertensive agents as...

patents.google.com

5-phenyl-2-thiaoxazoles-as-DA-inhibitors hosted at ImgBB

Image 5-phenyl-2-thiaoxazoles-as-DA-inhibitors hosted in ImgBB

ibb.co

 

[AlsoTapered]

'are useful as dopaminergic, antipsychotic, and antihypertensive agents as well as for treating hyperprolactinaemia-related conditions and central nervous system disorders.'

What a compound does in animal models isn't much of a guide to how it acts in man.

 

[AlsoTapered]

BTW this is just me, but I practice 'defensive design' which is why you will see me use the term 'sacrificial moiety' so often. Design a compound with a very clear metabolic weakness so you KNOW the body can use non-specific blood enzymes to remove it.

Things like MCAT are great examples. I don't think the designer THOUGHT of metabolism but that para-methyl is so readily oxidized that over 90% of the compound goes down that pathway.

If you design a novel compound, people are entirely placing their trust in your abilities. Since I am not in a position to run as many trials as I would wish, I feel I MUST use defensive design. 1 death is 1 to many. When 1 person was killed by U-47700 (I've posted the story) I quit... and had a nervous breakdown. I take a single death as my own fault.

So if I post a scaffold, believe me, I have spent months thinking about it and modelling it.

 

[paracelsius]

I know the sulphur is in a different position, but I came across a couple of papers that seems loosely relevant to this discussion and aminorex in general. While it appears that these scientists discovered a novel botanical alkaloid precursor, barbarin, after horses tested positive for aminorex that had not been exposed to levamisole, its not clear to me why they didn't consider another endogenous possibility. For example, phenylethanolamine is an endogenous precursor to aminorex found in the body in trace amounts and the consumption of plants containing cyanogenic compounds might well cyclize it to aminorex in situ. As atara pointed out, 2-aminothiazolines are formed in the body and one route is L-cysteine + cyanogenic compounds as I recall. In any event, I never was able to find out any more information regarding Thiaminorex (5-phenyl-2-aminothiazoline) or whether its even available, but I was excited to see this discussion because it was a molecule I had thought about years ago when pondering the possibility of a safer shorter acting aminorex compound.

Aminorex identified in horse urine following consumption of Barbarea vulgaris; a preliminary report​

Aminorex identified in horse urine following consumption of Barbarea vulgaris; a preliminary report - Irish Veterinary Journal

Background Aminorex, (RS)-5- Phenyl-4,5-dihydro-1,3-oxazol-2-amine, is an amphetamine-like anorectic and in the United States a Drug Enforcement Administration [DEA] Schedule 1 controlled substance. Aminorex in horse urine is usually present as a metabolite of Levamisole, an equine anthelmintic...

link.springer.com

Synthesis and characterization of barbarin, a possible source of unexplained aminorex identifications in forensic science​

https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/full/10.1002/dta.2883

Makes perfect sense. Yea I've seen those claims ie levamisole getting metabolized to aminorex to explain traces of aminorex found in horse urine. But I think it is bullshit. I mean I just dont see how Levamisole can get converted to aminorex. Most likely as you mentioned probably Aminorex seen come from Phenylethanolamine + some electrophilic cyanides found in some plants consumed by horses. The cyclization is very easy once the cyanamide is formed (NH+xCN->N-CN--veryfast--->oxazoline. I have yet to see reports of same thing happening in humans as 50%+ cocaine in the US is cut with levamisole.

Is it the oxazole or oxazoline ring and/or other molecular features that determines whether these thiaminorex derivatives are monoamine releasers/reuptake inhibitors or dopamine autoreceptor agonists?

No, the Oxa(thia)zoline ring doesnt affect much releasers/inhibitors: They're just a cyclized version of cathinones (X-MMC..) with the O and N joined (same conformation, superimpose perfectly). those are monoamines releasers rather than uptake inhibitors. Just like cathinones and pyros, increasing the lenght of 4-alkyl of 4-MAR from methyl to propyl - or butyl you go from releaser to uptake inhibitor (similar to cathinones -> pyros). One compound I found interesting in the original aminorex patent is 4-propyl-aminorex. I suspect no I am pretty sure this compound is reuptake inhibitor more cocaine-like than amph-like. We probably try again to make OP compound.

Aminorex exists as a a tautomer and so part of the time the primary amine is responsible for binding, part of the time the secondary amine.

you right probably in solution it might equilibrate between the endo and exo form. In solid state tho, only the endo tautomer exists iirc I mean in general 2-amino(oxa)thiazolines exists as endo ie amino rather than exo ie imino form.. On the other hand 3-methylaminorex (2-imino-3-methyl-5-phenyl-oxazoline) is as good as MDMA/meth, somewhere bewteen meth/mdma rather unique was bioassayed in Poland iirc Heard a lots great thing about that one. 1-step synth of this one is straihforward (N-methylphenylethanolamine + KNCO, hcl reflux)... The one using cheap Halostachine (chiral natural (R) N-Me-Phenylethanolamine) sold by chinese gives is no good I heard total bunk I heard, so I guess only one enantiomer (S) is active!! or at least racemate.. which makes senses from amphetamines SAR.

oh btw does anyone on here have access to reaxys? I am trying get ref for this rx: reductive desulfurization of dithiocarbamates by raney-nickel or nickel boride:
RSC(=S)-NHR ----> MeNHR + RH. If anybody come across something related, I'd be most grateful.
Thanks a lot . Good'Day All BLIghters. Stay Safe Out There

 

[AlsoTapered]

Please repeat reference. If I'm expected to find it, I think it's reasonable to know what I'm looking for.

 

[logos_rising]

The one using cheap Halostachine (chiral natural (R) N-Me-Phenylethanolamine) sold by chinese gives is no good I heard total bunk I heard

Based on plant extraction research with the related natural alkaloid Synephrine, the enantiomer that one gets might well vary with temperature (100c), time (20hr), and pH (10), but I could find no evidence that that research has been conducted with halostachine.

halo2 hosted at ImgBB

Image halo2 hosted in ImgBB

ibb.co

Separation of Synephrine Enantiomers in Citrus Fruits by a Reversed Phase HPLC after Chiral Precolumn Derivatization​

Separation of Synephrine Enantiomers in Citrus Fruits by a Reversed Phase HPLC after Chiral Precolumn Derivatization - Analytical Sciences

Racemic synephrine, which was transformed into diastereomers by derivatization with 2,3,4,6-tetra-O-acetyl-β-Dglucopyranosil isothiocyanate, was resolved by a reversed phase HPLC with UV detection at 254 nm. The total contents of synephrine enantiomers in citrus fruit samples were exocarp >...

link.springer.com

 

[paracelsius]

Please repeat reference. If I'm expected to find it, I think it's reasonable to know what I'm looking for.

Thanks @AlsoTapered for trying. I was actually trying get hold of "any" references dealing with reductive desulfurization of dithiocarbamates. desulfurisation of sulfur containing is pretty well known and general Rx (raney nickel or nickel boride would give hydrocarbons from bunch of mercaptans, sulfides, disulfides, dithianes, thioketones, thioamides..etc. Reason I was asking havent seen any ref dealing specifically with dithiocarbamates. related thioureas gives N-Methyl compounds like this: RNH(C=S)NHR--->RNHCH3 + RNH2. (cf here J Chem Soc Perkins Transactions I 2002, 2520-2524 ).

iirc one can input a generic Rx in Reaxys and it it would give references related to that, is that right? Used reaxys long time ago but now I dont have access have to travel hundred miles nearest univ library (oh btw we are looking at chiral synth of dextro-alfa-methyl-phenethylamine and its N-methyl homologs from OTC precursors.. optically pure dextros! am pretty sure you know what I am talking about... thx
nb: reductive desulfurization (not oxidative like with Hg salts)

Based on plant extraction research with the related natural alkaloid Synephrine, the enantiomer that one gets might well vary with temperature (100c), time (20hr), and pH (10), but I could find no evidence that that research has been conducted with halostachine.

halo2 hosted at ImgBB

Image halo2 hosted in ImgBB

ibb.co

Separation of Synephrine Enantiomers in Citrus Fruits by a Reversed Phase HPLC after Chiral Precolumn Derivatization​

Separation of Synephrine Enantiomers in Citrus Fruits by a Reversed Phase HPLC after Chiral Precolumn Derivatization - Analytical Sciences

Racemic synephrine, which was transformed into diastereomers by derivatization with 2,3,4,6-tetra-O-acetyl-β-Dglucopyranosil isothiocyanate, was resolved by a reversed phase HPLC with UV detection at 254 nm. The total contents of synephrine enantiomers in citrus fruit samples were exocarp >...

link.springer.com

Possible that related synephrine racemizes under the conditions you mentioned but I am not sure the same would happen with halostachine: The para hydroxy of synephrine (lacking in halostachine) (strongly!) activates the benzylic alcohol and makes it easy to racemize via corresponding "stable" benzylic cation. In fact the cis isomer of the methylenedioxy analog of 4-MAR (cis 3,4-DMAR) racemizes to the trans via similar mechanism after few minutes in water (will post ref later).

One thing is sure: the natural product (Halostachine) is chiral, whether it may racemize when doing CNBr Rx or KCN/HCl to oxazolines, I dont know. Most likely, the former will give chiral product; the latter (pretty harsh conditions (HCL/100C, 2-3h)might lead to racemic 3-MAR. On the other hand I wont be surprised only one isomer is active (or at least more than the other) so probably best to bioassay the racemic 3-MAR rather than pure enantiomer from halostachine. Notice tho, the 3-MAR (regardless chirality) might just not be as active as the 4-MAR or even plain aminorex!

Good'day all BLighters. Stay Safe Out There

 

[AlsoTapered]

Library Genesis

libgen.rocks

 

[logos_rising]

The para hydroxy of synephrine (lacking in halostachine) (strongly!) activates the benzylic alcohol and makes it easy to racemize via corresponding "stable" benzylic cation.

Thank you for responding. I was afraid you'd say that, but good to hear it from someone more knowledgeable than I. Why would HCL be more likely to racemize HAL (which doesn't work as well for SYN) than a base? Also, would ETOH as solvent (which doesn't work for SYN) be more suitable for racemizing HAL with HCL?

Apparently, research was conducted & published on this topic, but I can not locate the paper. If alsotapered or someone else has the means to located it, I would be most grateful.

STUDIES ON SYMPATHOMIMETIC AMINES. X. RACEMIZATION OF HALOSTACHINE AND PHENYLEPHRINE.​

Author: KISBYE J; MADSEN NB
R. DAN. SCH. PHARM., DK-2100 COPENHAGEN, DEN.
Source: ARCH. PHARM. CHEMI; DENM.; DA. 1977; VOL. 84; NO 18; PP. 911-918; BIBL. 8 REF. [German]