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Substituted Aminorex Series

3,4-methylenedioxy-aminorex is listed in the Poos et al paper from 1963, "2-amino-5-aryl-2-oxazolines. Potent New Anorectic Agents." Not sure what journal its from, was off the pdf archive at Rhodium.

Anyway they list the methylenedioxy derivative as compound XXXIII in the chart on the second page, says that the ED50 is 150mg/kg (compared to 5.8mg/kg for aminorex and 8.8mg/kg for 4-MAR).

So looks pretty weak as an anorectic agent in rats at any rate, which implies that its stimulant / serotonin releasing effects would also be weak. Doesn't look like they tested the 4-MAR analogue though.
 
Actually, the lad I knew said that the first couple of times it was great, but by about half a dozen tries it had 'lost the magic' abd instead of increased empathy etc, it was just a very freaked out, somewhat overstimulated feeling of emptyness. Even giving it a break and not having any for a fair few months still resulted in the above unpleasant reaction (that might just be a reason it's never even had much small scale 'clandestine' production)
 
^What was the potency like compared with 'plain vanilla' 4MAR? p-F AR is 4x as potent as it's parent... but potency isn't everything... legality is, though!
 
Hi!

I got told by a friend "the guys at bluelight said basically eveyrthing with a naphthyl group was made and they moved on to larger rings like acenapththene".
He was talking about stimulant drugs in general, not just this one with this remark, but it touched the topic..

Thought this would be the most suitable thread to post this in, because I made the substance 2-amino-5-(naphth-2-yl)-2-oxazoline(it received the cool name naphthaminorex) very few years ago, twice actually, small amounts because of the losses and tiny amounts of precursors made by me trying different ways to get there.
But to my knowledge, it is absolutely unknown in the literature, as are any similar 2-naphthyl substituted analogues from that class.
I found absolutely nothing for this, but it was straight forward to make unlike 4-MAR analogues who suck and their yields do too.

In my impression it felt quite well balanced, dopaminergic predominantly, but had an empathogenic touch.
Swisstargetprediction is not very useful, they base their assumptions only on known molecules and not what could be really possible based on the functional.
It comes out as dopamine agonst, because it contains aminorex substructure, pretty useless for me.

Anyone can add some more qualified thoughts about its likely mechanism of action?
A subjective impression is only so little worth, especially when you're aware you're trying a new drug out that you might have made as the first,
Thats already something special that doesn't happen every day, and is pretty exciting in itself.
And until that will be made and tried again, I'd like to find out a bit more.
I'm aware about the potential for a cancerogenic epoxide as metabolite, like pronethalol analogues cause(a pronethalol analogue/precursor itself was made and used for the substance).

Usually, the 2-naphthyl substituted analogues of a certain class, if ever made, are situated on top among maybe the 3,4-dichlorophenyl analogues, but thats it for those on top.
Its slightly different with the aminorex analogues, since those are pretty nice and strong already yet as C2 analogues from hydroxylated phenthylamines, but probably are not that easily broken up metabolically at first-pass.

But 2-phenylmorpholines are less resistant to metabolic breakdown than that usually, if not having the 3-methyl group.
I mention those, because US 20130203752A1 contains also two 2-Napthylsubstituted analogue, one of them,
PAL-704, is unsurprisignly, in the end one of the two most remarkably acting ones in that paper(the other, neither surprising, the 3,4-dichloro analogue).
The analogue lackings its 3-methylgroup(PAL.703) does not appear as interesting and remarkble.
Thats not as true for aminorex and analogue as well as this one, although it appeared to me not as potent, unlike to the other tester.
Maybe half that of aminorex I would say.
Else there are very few cathinone analogues, and just as few for the amphetamines, even cocaine, and usually they have a seemingly quite pleasurable pharmacological profile when they have a 2-naphthyl group in place of phenyl.
Not controlled, arguably maybe not even if under analogue laws.

Any thoughts or comments?
 
My only comment is to welcome you here and to say you obviously don’t sound like Carl ;) (his posts at times frustratingly and cryptically short n sweet.)

I wish I could hang in this conversation but I can’t.

-GC
 
Welcome and thanks for this contribution! That's cool that you made and tested something new.

I am really interested in aminorex analogues. I have never had a chance to try 4-MAR, but it has always sounded like a pretty ideal stimulant to me. Until recently though, no analogues had hit the commercial scene. However, lately there have been 4-4-DMAR (some reports of cardiotoxicity potential, and some negative reviews but also some strong positive reviews), as well as 4,4-FMAR, as well as the Cl and Br versions of that. The halogenated ones sound decent, I wanted to give them a try myself but minimum order quantity is 5g unless you want to spend WAY too much for 1g and... yeah, I don't need 5 grams. I contacted the place to ask if I could do 5 grams mix and match of all 3, but they were unwilling to do that.

In any case I hope more aminorex analogues are explored and made available. I am particularly interested to see what would happen when the 2,5-dimethoxy-4-X substitution pattern is explored, that for amphetamines results in wonderful full spectrum psychedelics that are among the finest substances in all the land. Of course the same might not hold true for aminorex analogues, but I'm really curious to know.
 
My only comment is to welcome you here and to say you obviously don’t sound like Carl ;) (his posts at times frustratingly and cryptically short n sweet.)

I wish I could hang in this conversation but I can’t.

-GC
Phew what a relief, that means I'm inkognito :cool:
Cryptical! :oops:
I mean, not that I care, as I am obviously not that person.

But that guy sounds like an asshat with protruding ears, and..., and screw this guy too, yeah!
I wholeheartedly agree :p

I've not yet found out who you are though :p
Welcome and thanks for this contribution! That's cool that you made and tested something new.

I am really interested in aminorex analogues. I have never had a chance to try 4-MAR, but it has always sounded like a pretty ideal stimulant to me. Until recently though, no analogues had hit the commercial scene. However, lately there have been 4-4-DMAR (some reports of cardiotoxicity potential, and some negative reviews but also some strong positive reviews), as well as 4,4-FMAR, as well as the Cl and Br versions of that. The halogenated ones sound decent, I wanted to give them a try myself but minimum order quantity is 5g unless you want to spend WAY too much for 1g and... yeah, I don't need 5 grams. I contacted the place to ask if I could do 5 grams mix and match of all 3, but they were unwilling to do that.

In any case I hope more aminorex analogues are explored and made available. I am particularly interested to see what would happen when the 2,5-dimethoxy-4-X substitution pattern is explored, that for amphetamines results in wonderful full spectrum psychedelics that are among the finest substances in all the land. Of course the same might not hold true for aminorex analogues, but I'm really curious to know.
Thank you!(both)

Well, the thing with 4-MAR is, that it actually is not that great.
Since it happens to come, or is said to come in, a nice crystalline shape, and since it is also said to act like meth(it really, really does not), it often happens that some tweakers get sold, for the first time ever, some nicely shaped crystals.
And of course it is better than what they usually take.
Because of that, they come to the conclusion it must be 4-MAR.
There are quite a few reports on erowid which start something like that.

I found it disappointing, overly long acting, boring(yes) and it lacks the euphoria it is named after.
I also think, that the likelyhood of it developing pulmonary hypertonia is greater than it is for plain aminorex.
It really is not that great, there is some sort of mysterical aura around it, like it surrounds few drugs, and mostly those who are not accessible.
Other examples would be mephedrone, but only after it got banned, and phenmetrazine, which now have similar mysteriously good effects attached to them.
I mean, sure, phenmetrazine is great, but nobody mentions the high dosage required, because nobody has any real world experience with it.
Not talking about mephedrone at all, thats really bad.
If I want to be really down and depressed the next day, without getting much in return, I would do something else thats stupid but doesn't cost lots of money(sorry no good comparison for that, nobody wants that).

So in short, the aminorex analogues are much more interesting.
They don't act longer than a half day until you can sleep, and especially aminorex itself is quite euphoric and abuseable.
If you're not a fat old lady, it is also not really dangerous, but people tend to forget to which audience it got prescribed to for the most par.

There is also another thing involved, which has to do with its strange aphrodisiac action in especially postmenopausal women.... I don't know much about it though, but its fascinating.
It also has the ability to restore the libido, not just in postmenopausal women, but also men who got limp-dickedness due to old age or what, as I got told.
Can't confirm this either.
Although its not shrinking as amphetamine(s) tends to, or not that much.

However, its relation between effective and deadly dose is not that large as it is with other drugs, there is a paper
out describing 30 overdoses, all between 1-2mg/kg, even up to a small child(or several, no idea, its just mentioned that it doesn't causes lasting damage in those people, nobody died either, however, that was with pills and not the pure substance).
It should be treated with much consideration, as it actually was the cause of quite a few deaths, but properly dosed its not bad at all.

haribo1 surely could confirm this all.-

So, in case there are any research drugs around, they will definitely kill people, if they are 4-MAR analogues.
They are less likely to kill (as much) people as aminorex analogues.
Both is true.
If I would own a conscience, I wouldn't sell those.
But then again, nothing else either, because I'm in the possession of said conscience.
Guess other people come to different conclusions and thats why they hit the streets.

However, what interests me are the aminorex analogues only.
I've seen the forensic paper about 3,4-MD-4-MAR or MDMAR as they call it, and all the follow ups of that too, including the receptor affinity assay.
That was quite interesting, but as said, I suspect the 4-methyl group to be much more dangerous than most people think.

After all, aminorex caused pulmonary hypertony in fat old women.
But 4-MAR did the same in that small uncle, aunt, nephew family in, where was it, ohio?
It of course has a genetical predisposition, but you just don't randomly develope this in your early twentys even if you do coke, meth(or aminorex) like there's no tomorrow.
But 4-MAR caused this.
And also, it was discovered a bit, I think three years, earlier than Poos et al wrote his papers about these.
Why have they not marketed this analogue, but brought aminorex on the market instead?
To me its apparent, that they knew about some of these things.
Lets not forget that thalidomide(great sleeping pill) was still brought on the market after one of its inventors brought some home for his pregnant wife, and his xhild got born without ears.
That girl was in school before the medication was finally pulled off the market.
They knew there was something very badly wrong, but did not care.
Why should it be different with aminorex?
They likely knew it was less harmless than 4-MAR, but they likely also knew, that neither of them or any of the other analogues was completely harmless at all for the targetted part of the population.

Well anyways, it is a nice and underestimated drug, and everyone thinks 4-MAR which I can only sarcastically call "euphoria", is as good as some reports make it out to be.
Its interesting for sure, and definitely has the one or other use, but it is not that.
It will be a disappointment if thats whats expected.

For this reason, I actually do not hope any of these things appear on the market anymore.
Its like a trap full of honey, people will try them, be disappointed, take some more and more, and five days later their parents bury them.
And in turn, bad press for these drugs.

But I would definitely also like to try some of the other two carbon analogues instead.
Not the 2,5-diMeO though, but I think, after these "MDMAR" papers got published, that the analogue without the 4-methyl could be of interest.
I just happened to have the naphthyl precursor, and in turn found the idea so interesting, and the smell of the precursor also very nice, I had to follow it all the way to the end.

Although if people just would know how accessible these things are.... they would be astonished.
 
Anybody having experiences with 4F/Br/Cl-4'-MAR? These are now available in 1g quantities from a reputable EU vendor, and I'm going to buy if one or all are even just remotely like 4,4'-DMAR but we had another derivate, forgot which one, which was said to be primarily noradrenergic, which isn't what I am looking for.
 
Anybody having experiences with 4F/Br/Cl-4'-MAR? These are now available in 1g quantities from a reputable EU vendor, and I'm going to buy if one or all are even just remotely like 4,4'-DMAR but we had another derivate, forgot which one, which was said to be primarily noradrenergic, which isn't what I am looking for.
I'd be scared of using the that 4-Chloro-MAR, given how toxic 4CA is.
Maybe someone can chime in on how dangerous it would be?
 
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I'd be scared of using the that 4-Chloro-MAR, given how toxic is 4CA.
Maybe someone can chime in on how dangerous it would be?
This is a point indeed, I stood clear of the chlorinated cathinones for the same reason but it seems like people use them without damage (?)

Guess I'll order the fluoro one when the shop opens again.
 
I have a bunch of these. I haven't run them through STP yet but I have no doubts whatsoever that they'll work and some of them are absolute stonkers.

Also not just the crappy 4-F/Cl/Br analogues either, some really nice ones that (unfortunately as STP shows fuck all on the subject) look fairly identical to 4-MAR.

However some look good as just a normal stim/empath so I'll have a look through and find some of the better ones.

I always thought 4-EAR was the best analogue ever...I mean 4-EAR; Forear; Euphoria.
Anyway, I'll put it through now and see how it does (I made it way before STP was a thing).

EDIT:
4-MAR vs. 4-EAR (+ 4-MANR & 4-OAR)

Well, it seems like you're right; only the Methyl is dopaminergic to any degree. I mean the rest of 4-EAR seems like quite a nice compound but it's no stimulant certainly.

Ok...this is a working theory but Cytochrome P450 plus anything else enhances the activity of it. So TAAR1, Adenosine A1 & 2, GABA-a, HT6 and Dopamine Transporter are all enhanced by the P450 (not sure which one but 2A6 crops up a lot of the time) /plus/ MAO-A inhibition would make a mean stimulant.

So looking at 4-EAR, it looks more like a downer than an upper. I mean there's a lot of GABA-a, Anandamide, TAAR1, MGlur5, HT6, H3&4 and even Muscarine 1!

Weird..right?!

EDIT: I added in 4-OAR and 4-MANR and it seems like 4-OAR would be quite a good candidate for a novel aminorex. 4-MANR looks interesting too, not as a stimulant mind you but it's...strangely alluring...
 
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"MDMAminorex" this idea has been thought about countless times, aminorex analogs dont follow the same rules as amphetamines, the MD versions aren't really anygood, they've been made i think
No it doesn't. It's most certainly possible to ring-substitute for selective SERT, selective DAT, balanced SERT/DAT & for 5HT2a affinity. The former are very simple, the latter only works with a small subset of Pihkal substitutions. Substitution at the ortho positions seems to make inactive compounds. 3,4-MDAR is only slightly active .

However, it's important not to assume that because a ring-substituted 4MAR is inactive, the same ring-substituted AR will likewise be inactive. The extra chiral centre might mean that only 25% or even 0% (depending on routes) of the 4MAR is of the correct conformation.
I note that far more 4MAR derivatives than AR derivatives are showing up. I presume that this is because few people are prepared to work with BrCN at scale. KOCN will not form the ring but rather produces the substituted urea. I suspect that this intermediate can be cyclized, although I haven't mined the papers/patents.

But GOOD NEWS! There is a safe & convenient alternative to BrCN in the shape of NaHNCN.

I'm sure people will not have any difficulty in finding routed to the intermediate amino-alcohol. The appropriate benzaldehyde will readily form the nitro-alcohol but it's a VERY common reaction-scheme and I am sure you will be able to find one you are happy with.

Personally I like 3,4,5 trimethoxyaminorex although others like the 3,5-dimethoxy-4-alkyls derivatives. When choosing, remember that almost all of the metabolism is via the ring or ring substituents. 3-MeO-4-Me is a decent MDMA-like compound but it's duration is rather long. I would be interested to know if the 3-MeS-4-Me is an improvement.

So, RCs have looked at ALMOST all classes of stimulant but I have yet to see any mazindol derivatives. If memory serves, expanding the imidazoline ring to a 2,3,4,6-tetrahydropyrimido increases DAT activity by an order of magnitude. I have often wondered about the presence of the p-Cl & the 6-OH moieties. I suggest the former is to prevent metabolism & the -OH is to provide a specific point FOR metabolism.

Don't forget how old mazindol is. Pipradrol is from the same era & the -OH in that case was most certainly to aid in metabolism.
 
3, 4-MDO-4-MAR

It's alright...I spose..absolutely no dopaminergicity or serotonergicity though.

I was wondering about this years and years ago, then kinda started thinking logically about it and how 4-MAR isn't exactly a PEA, therefore it won't follow the rules of PEAs.
 
3, 4-MDO-4-MAR

It's alright...I spose..absolutely no dopaminergicity or serotonergicity though.

I was wondering about this years and years ago, then kinda started thinking logically about it and how 4-MAR isn't exactly a PEA, therefore it won't follow the rules of PEAs.

I think it's only going to have NET affinity. Plain 3,4-MD AR might be a better target. As I pointed out, that methyl side-chain increases the biosteric minimum. MAR & 4MAR have totally different QSARs and as I mentioned, while AR has 2 isomers, 4MAR has 4 isomers and apart from their being a widely known synthesis for 4MAR, it has no advantages. Actually, their is a second, evcen simpler route to 4MAR.

US3052688A - PROCESS FOR THE PRODUCTION OF 2-AMINO-OXAZOLES

The above is of great utility. After all, it allows the uncontrolled precursor L-PAC to be directly concerted to 4MAR.

I'm not interested in such compounds. A few ring-substituted ARs are of interest but 4MAR is a pleasant stimulant but I've seen the harm caused by such compounds and the (M)AR class also cause heart-valve damage so it's not something I would get involved with.

Still, if L-PAC is suddenly made a controlled precursor, we will know that the DEA reads these pages.... so hello!
 
Wouldn't it be morelike Phenmetrazine than 4-MAR? I mean there isn't much of a difference except in supposed power (by the way, is 4-MAR /actually/ like Meth x10 (well, 2-4x max!) because looking at the SAR it certainly has the potential but IRL does it actually work out?!).

EDIT; I'm not even sure what I was relating phenmet to...I'm really stoned. I'll sort this post out later.
 
Stimulants act on the VMAT 2 & their are 2 distinct binding sites. Similar compounds can bind differently. Amphetamine binds to one of them, methamphetamine the other. I suspect other stimulants bind to both but in different ratios.

Cypenamine is an interesting one - it's more or less just 1 ring of fencamfamine/camfetamine (minus N-alkyl).

I know fencamfamine is very euphoric and would expect cypenamine (or it's N-methyl or N-ethyl derivative) to be very similar. The reasons seems to be that they have little to no NET activcity.

For those who like a puzzle - why does amfonelic acid act like cocaine? The DAT transport must be VERY complex. Oh, if people want an OTC compound like amfonelic acid, oxalinic acid (AKA antibiotic for fish) is very similar. Getting the dose right requires slowly building up the dose and accepting that side-effects will limit dose. Some Dutch friends tried it out over a couple of months....
 
I know fencamfamine is very euphoric and would expect cypenamine (or it's N-methyl or N-ethyl derivative) to be very similar. The reasons seems to be that they have little to no NET activcity.

I've had n-methyl-cypenamine and n-ethyl-cypenamine, and both were very lackluster, in fact it was early so weak as to be possibly placebo. Though that doesn't mean plain old cypenamine wouldn't be a different story.
 
N ethyl cypenamine is reported to be not that great, camphetamine and fencamfamin are great though. Not really potent but a nice mellow high without much abuse Potential. Bad decision to put it off the market.
 
I'd be scared of using the that 4-Chloro-MAR, given how toxic 4CA is.
Maybe someone can chime in on how dangerous it would be?

The duration of ALL AR & MAR with (pseudo)halogen ring-substitutions is very long indeed. p-hydroxylation is the major way the body metabolises this class. Someone has studied all manner of 4-alkyl aminorex derivatives and some o-halogenated analogues.

DOI: 10.1021/acschemneuro.8b00415

The paper also provides the EC50 for NET ,DAT & SERT inhibition and release. You will note p-F>p-Cl>p-F. Sadly, most RC chemists simply look for the most potent because it translates into the most profitable. p-Me 4MAR was sold as 'Serotonia' but while it had plenty of SERT activity, it doesn't have enough DAT (or NET, if you like NET inhibition/release). I didn't try it myself, but I have tried p-Me Aminorex and my wife has tried both and was firm on the matter that p-Me AR was the better.

What you actually want is a mixture of the p-Me with another analogue that has DAT activity and importantly, a duration as close to the p-Me as possible.

Oh, and the reason that the 4MARs seem to turn up a lot more often is that they are synthetically simpler. I must admit that their use of sodium diformylamide followed by NaBH4 reduction is a MUCH cleaner method than the crappy SN2 reaction generally seen. Of course, they seill use BrCN for the cyclization. It IS more convenient, but I would rather go with:

DE Patent 2101424

Styrene oxide is commercially available & cheap but if you want to produce a ring-substituted analogue, you will have to obtain the substituted styrene & oxidize it (there are MANY methods). They offer both the cyanamide & guanidine routes to cyclization.

I've also come across another, Polish (I think) route to make AR but it was 20 years ago so all I remember is that it was a Polish paper AND I had to contact a Polish library of chemical papers to obtain it. It wasn't much good but it brings the total number of routes up to 6. I mean, people like Uncle Fester have stretched 6 routes into an entire book.
 
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